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CitationGPTv2_test

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CitationGPTRetr500

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs? Abstract of the paper: Histone deacetylase (HDAC) inhibitors have been demonstrated to be beneficial in animal models of neurodegenerative diseases. Such results were mainly associated with the epigenetic modulation caused by HDACs, especially those from class I, via chromatin deacetylation. However, other mechanisms may contribute to the neuroprotective effect of HDAC inhibitors, since each HDAC may present distinct specific functions within the neurodegenerative cascades. Such an example is HDAC6 for which the role in neurodegeneration has been partially elucidated so far. The strategy to be adopted in promising therapeutics targeting HDAC6 is still controversial. Specific inhibitors exert neuroprotection by increasing the acetylation levels of α-tubulin with subsequent improvement of the axonal transport, which is usually impaired in neurodegenerative disorders. On the other hand, an induction of HDAC6 would theoretically contribute to the degradation of protein aggregates which characterize various neurodegenerative disorders, including Alzheimer's, Parkinson's and Hutington's diseases. This review describes the specific role of HDAC6 compared to the other HDACs in the context of neurodegeneration, by collecting in silico, in vitro and in vivo results regarding the inhibition and/or knockdown of HDAC6 and other HDACs. Moreover, structure, function, subcellular localization, as well as the level of HDAC6 expression within brain regions are reviewed and compared to the other HDAC isoforms. In various neurodegenerative diseases, the mechanisms underlying HDAC6 interaction with other proteins seem to be a promising approach in understanding the modulation of HDAC6 activity.

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CitationGPTRetr501

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: The promise and perils of HDAC inhibitors in neurodegeneration. Abstract of the paper: Histone deacetylases (HDACs) represent emerging therapeutic targets in the context of neurodegeneration. Indeed, pharmacologic inhibition of HDACs activity in the nervous system has shown beneficial effects in several preclinical models of neurological disorders. However, the translation of such therapeutic approach to clinics has been only marginally successful, mainly due to our still limited knowledge about HDACs physiological role particularly in neurons. Here, we review the potential benefits along with the risks of targeting HDACs in light of what we currently know about HDAC activity in the brain.

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CitationGPTRetr502

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Histone deacetylase inhibitors: possible implications for neurodegenerative disorders. Abstract of the paper: During the past six years numerous studies identified histone deacetylase (HDAC) inhibitors as candidate drugs for the treatment of neurodegenerative disorders. Two major neuroprotective mechanisms of HDAC inhibitors have been identified, namely the transcriptional activation of disease-modifying genes and the correction of perturbations in histone acetylation homeostasis, which have been shown to be intimately involved in the neurodegenerative pathomechanisms of Huntington's, Parkinson's and Kennedy disease, amyotropic lateral sclerosis, Rubinstein-Taybi syndrome as well as stroke. Based on the promising in vitro and in vivo analyses, clinical trials have been initiated to evaluate the safety and efficacy of HDAC inhibitors for the treatment of devastating diseases such as Huntington's disease, amyotropic lateral sclerosis and spinal muscular atrophy. Here, the authors summarize and discuss the findings on the emerging field of epigenetic therapy strategies in neurodegenerative disorders.

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CitationGPTRetr503

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Histone deacetylases as targets for the treatment of neurodegenerative disorders: Challenges and future opportunities. Abstract of the paper: Despite the applicability of histone deacetylase inhibitors (HDACis) for cancer treatment, several works in the literature have shown that these inhibitors can be used in several other diseases, such as neurodegenerative diseases (NDs). This review begins by discussing the signaling pathways of HDACs, focused on the context of NDs, presenting a discussion about the pharmacophoric features of HDACis and crystal structure analysis and discussing interesting case studies from the literature about the development of HDACis. Additionally, a discussion about the consequences of isoform-selective inhibition vs pan-HDACis on neurotoxic effects and clinical trial investigations of HDACis for NDs is also presented. Finally, we describe our perspective related to the future use of these inhibitors in the pharmacotherapy of NDs.

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CitationGPTRetr504

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Epigenetics in Neurodegenerative Diseases: The Role of Histone Deacetylases. Abstract of the paper: BACKGROUND & OBJECTIVE Imbalance in histone acetylation levels and consequently the dysfunction in transcription are associated with a wide variety of neurodegenerative diseases. Histone proteins acetylation and deacetylation is carried out by two opposite acting enzymes, histone acetyltransferases and histone deacetylases (HDACs), respectively. In-vitro and in-vivo animal models of neurodegenerative diseases and post mortem brains of patients have been reported overexpressed level of HDACs. In recent past numerous studies have indicated that HDAC inhibitors (HDACIs) might be a promising class of therapeutic agents for treating these devastating diseases. HDACs being a part of repressive complexes, the outcome of their inhibition has been attributed to enhanced gene expression due to heightened histone acetylation. Beneficial effects of HDACIs has been explored both in preclinical and clinical studies of these diseases. Thus, their screening as future therapeutics for neurodegenerative diseases has been widely explored. CONCLUSION In this review, we focus on the putative role of HDACs in neurodegeneration and further discuss their potential as a new therapeutic avenue for treating neurodegenerative diseases.

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CitationGPTRetr505

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Multiple roles of HDAC inhibition in neurodegenerative conditions. Abstract of the paper: Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. A wide range of brain disorders are associated with imbalances in protein acetylation levels and transcriptional dysfunctions. Treatment with various HDAC inhibitors can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative disease. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties; improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in the treatment of neurodegenerative disorders.

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CitationGPTRetr506

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Histone deacetylase inhibitors and neurodegenerative disorders: holding the promise. Abstract of the paper: Neurodegenerative disorders (NDs) such as Huntington's disease, Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, spinal muscular atrophy, Friedreich's ataxia, and others are multi-factorial illnesses, in which many pathways (still poorly understood) act serially and in parallel to give a determined pathologic phenotype. Thus, presently there are no effective cures for these diseases. Some phenotypic as well as mechanistic features, common to the most of NDs, can be linked to epigenetic defects, that can lead to alteration of acetylation homeostasis and impairment of the histone acetyltransferase (HAT): histone deacetylase (HDAC) balance. Here we survey most of the recent applications of HDAC inhibitors in the cited NDs, and we make the point of our (up to now) knowledge about the involvement of singular HDAC/SIRT isoform in NDs and other CNS pathologies.

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CitationGPTRetr507

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Although HDAC inhibitors have the ability to ameliorate cognitive impairment, successful treatments in the classic AD animal model are rarely translated into clinical trials. As for the reduction of unwanted side effects, the development of HDAC inhibitors with increased isoform selectivity or seeking other directions is a key issue that needs to be addressed. The review focused on literatures on epigenetic mechanisms in recent years, especially on histone acetylation in terms of the enhancement of specificity, efficacy and avoiding side effects for treating AD.

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CitationGPTRetr508

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: New prospects and strategies for drug target discovery in neurodegenerative disorders. Abstract of the paper: The future of neurodegenerative therapeutics development depends upon effective disease modification strategies centered on carefully investigated targets. Pharmaceutical research endeavors that probe for a much deeper understanding of disease pathogenesis, and explain how adaptive or compensatory mechanisms might be engaged to delay disease onset or progression, will produce the needed breakthroughs. Below, we discuss the prospects for new targets emerging out of the study of brain disease genes and their associated pathogenic pathways. We describe a general experimental paradigm that we are employing across several mouse models of neurodegenerative disease to elucidate molecular determinants of selective neuronal vulnerability. We outline key elements of our target discovery program and provide examples of how we integrate genomic technologies, neuroanatomical methods, and mouse genetics in the search for neurodegenerative disease targets.

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CitationGPTRetr509

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Targeting the correct HDAC(s) to treat cognitive disorders. Abstract of the paper: Changes in gene expression in the brain may underlie cognitive deficits inherent to normal aging and neurodegenerative disease. However, the mechanisms underlying pathological alterations in the brain transcriptome are incompletely understood. Epigenetic mechanisms such as DNA methylation and histone acetylation have been shown to be important for memory processes in the adult brain. There is accumulating evidence that altered chromatin plasticity and histone acetylation are also involved in cognitive aging, neurodegeneration, and neuropsychiatric diseases. Inhibitors of histone deacetylase (HDAC) exhibit neuroprotective and neuroregenerative properties in animal models of various brain diseases. As such, targeting of HDACs seems to be a promising therapeutic strategy. In this review, we discuss the specific roles of each HDAC protein and the possible function of distinct histone modifications. We hope that this knowledge will aid in the development of diagnostic tools and in designing more potent and specific treatment for neurological disorders targeting selective HDAC proteins.

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CitationGPTRetr510

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease. Abstract of the paper: Histone deacetylases (HDACs) are currently being discussed as promising therapeutic targets to treat neurodegenerative diseases. However, the role of specific HDACs in cognition and neurodegeneration remains poorly understood. Here, we investigate the function of HDAC6, a class II member of the HDAC superfamily, in the adult mouse brain. We report that mice lacking HDAC6 are cognitively normal but reducing endogenous HDAC6 levels restores learning and memory and α-tubulin acetylation in a mouse model for Alzheimer's disease (AD). Our data suggest that this therapeutic effect is, at least in part, linked to the observation that loss of HDAC6 renders neurons resistant to amyloid-β-mediated impairment of mitochondrial trafficking. Thus, our study suggests that targeting HDAC6 could be a suitable strategy to ameliorate cognitive decline observed in AD.

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CitationGPTRetr511

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Targeting HDACs: a promising therapy for Alzheimer's disease. Abstract of the paper: Epigenetic modifications like DNA methylation and histone acetylation play an important role in a wide range of brain disorders. Histone deacetylases (HDACs) regulate the homeostasis of histone acetylation. Histone deacetylase inhibitors, which initially were used as anticancer drugs, are recently suggested to act as neuroprotectors by enhancing synaptic plasticity and learning and memory in a wide range of neurodegenerative and psychiatric disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). To reveal the physiological roles of HDACs may provide us with a new perspective to understand the mechanism of AD and to develop selective HDAC inhibitors. This paper focuses on the recent research progresses of HDAC proteins and their inhibitors on the roles of the treatment for AD.

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CitationGPTRetr512

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: The potential of epigenetic therapies in neurodegenerative diseases. Abstract of the paper: Available treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, do not arrest disease progression but mainly help keeping patients from getting worse for a limited period of time. Increasing evidence suggests that epigenetic mechanisms such as DNA methylation and histone tail modifications are dynamically regulated in neurons and play a fundamental role in learning and memory processes. In addition, both global and gene-specific epigenetic changes and deregulated expression of the writer and eraser proteins of epigenetic marks are believed to contribute to the onset and progression of neurodegeneration. Studies in animal models of neurodegenerative diseases have highlighted the potential role of epigenetic drugs, including inhibitors of histone deacetylases and methyl donor compounds, in ameliorating the cognitive symptoms and preventing or delaying the motor symptoms of the disease, thereby opening the way for a potential application in human pathology.

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CitationGPTRetr513

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Remodeling chromatin and stress resistance in the central nervous system: histone deacetylase inhibitors as novel and broadly effective neuroprotective agents. Abstract of the paper: Acetylation and deacetylation of histone protein plays a critical role in regulating gene expression in a host of biological processes including cellular proliferation, development, and differentiation. Accordingly, aberrant acetylation and deacetylation resulting from the misregulation of histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) has been linked to clinical disorders such as Rubinstein-Taybi syndrome, fragile X syndrome, leukemia, and various cancers. Of significant import has been the development of small molecule HDAC inhibitors that permit pharmacological manipulation of histone acetylation levels and treatment of some of these diseases including cancer. In this Review we discuss evidence that aberrant HAT and HDAC activity may also be a common underlying mechanism contributing to neurodegeneration during acute and chronic neurological diseases, including stroke, Huntington's disease Amyotrophic Lateral Sclerosis and Alzheimer's disease. With this in mind, a number of studies examining the use of HDAC inhibitors as therapy for restoring histone acetylation and transcriptional activation in in vitro and in vivo neurodegenerative models are discussed. These studies demonstrate that pharmacological HDAC inhibition is a promising therapeutic approach for the treatment of a range of central nervous system disorders.

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CitationGPTRetr514

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Inhibition of Histone Deacetylase 6 (HDAC6) as a therapeutic strategy for Alzheimer's disease: A review (2010-2020). Abstract of the paper: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, which is characterized by the primary risk factor, age. Several attempts have been made to treat AD, while most of them end in failure. However, with the deepening study of pathogenesis of AD, the expression of HDAC6 in the hippocampus, which plays a major role of the memory formation, is becoming worth of notice. Neurofibrillary tangles (NFTs), a remarkable lesion in AD, has been characterized in association with the abnormal accumulation of hyperphosphorylated Tau, which is mainly caused by the high expression of HDAC6. On the other hand, the hypoacetylated tubulin induced by HDAC6 is also fatal for the neuronal transport, which is the key impact of the formation of axons and dendrites. Overall, the significantly increased expression of HDAC6 in brain regions is deleterious to neuron survival in AD patients. Based on the above research, the inhibition of HDAC6 seems to be a potential therapeutic method for the treatment of AD. Up to now, various types of HDAC6 inhibitors have been discovered. This review mainly analyzes the HDAC6 inhibitors reported amid 2010-2020 in terms of their structure, selectivity and pharmacological impact towards AD. And we aim at facilitating the design and development of better HDAC6 inhibitors in the future.

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CitationGPTRetr515

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders. Abstract of the paper: INTRODUCTION Epigenetic modifications, such as histone acetylation and deacetylation, are responsible for maintaining chromatin stability. As such, they have been implicated in a wide range of neurodegenerative disorders. METHODS Histone acetylation involves the presentation of an acetyl group to lysine residues at the N terminus of histone proteins. Conversely, histone deacetylation involves the detachment of acetyl groups. Transcriptionally active chromatin is linked to acetylated histones, and in mouse neurons, is implicated in proper learning and memory. DISCUSSION Proper functioning of histone deacetylases (HDACs) plays a pivotal role in histone acetylation homeostasis. RESULTS A wide range of brain disorders are associated with improper balances within histone acetylation mechanisms, resulting in transcriptional dysfunction and translational disparities. Treatment modalities with various HDAC inhibitors have emerged as potential new strategies for therapeutic intervention in neurodegenerative disease. HDAC inhibitors enhance synaptic plasticity, learning and memory in neurodegenerative disorders, such as Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). In this review, we discuss a variety of in vitro cellular models and in vivo mouse models of neurodegenerative diseases and the potential application of HDAC inhibitors to prevent and treat these disorders.

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CitationGPTRetr516

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: The cytoskeleton as a novel therapeutic target for old neurodegenerative disorders. Abstract of the paper: Cytoskeleton defects, including alterations in microtubule stability, in axonal transport as well as in actin dynamics, have been characterized in several unrelated neurodegenerative conditions. These observations suggest that defects of cytoskeleton organization may be a common feature contributing to neurodegeneration. In line with this hypothesis, drugs targeting the cytoskeleton are currently being tested in animal models and in human clinical trials, showing promising effects. Drugs that modulate microtubule stability, inhibitors of posttranslational modifications of cytoskeletal components, specifically compounds affecting the levels of tubulin acetylation, and compounds targeting signaling molecules which regulate cytoskeleton dynamics, constitute the mostly addressed therapeutic interventions aiming at preventing cytoskeleton damage in neurodegenerative disorders. In this review, we will discuss in a critical perspective the current knowledge on cytoskeleton damage pathways as well as therapeutic strategies designed to revert cytoskeleton-related defects mainly focusing on the following neurodegenerative disorders: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis and Charcot-Marie-Tooth Disease.

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CitationGPTRetr517

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements. Abstract of the paper: For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to chromatin condensation followed by transcriptional repression. HDACs are divided into distinct classes: I, IIa, IIb, III, and IV, on the basis of size and sequence homology, as well as formation of distinct repressor complexes. Implications of HDACs in many diseases, such as cancer, heart failure, and neurodegeneration, have identified these molecules as unique and attractive therapeutic targets. The emergence of HDAC4 among the members of class IIa family as a major player in synaptic plasticity raises important questions about its functions in the brain. The characterization of HDAC4 specific substrates and molecular partners in the brain will not only provide a better understanding of HDAC4 biological functions but also might help to develop new therapeutic strategies to target numerous malignancies. In this review we highlight and summarize recent achievements in understanding the biological role of HDAC4 in neurodegenerative processes.

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CitationGPTRetr518

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Abstract of the paper: Histone deacetylases (HDACs)--enzymes that affect the acetylation status of histones and other important cellular proteins--have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Pharmacological manipulations using small-molecule HDAC inhibitors--which may restore transcriptional balance to neurons, modulate cytoskeletal function, affect immune responses and enhance protein degradation pathways--have been beneficial in various experimental models of brain diseases. Although mounting data predict a therapeutic benefit for HDAC-based therapy, drug discovery and development of clinical candidates face significant challenges. Here, we summarize the current state of development of HDAC therapeutics and their application for the treatment of human brain disorders such as Rubinstein-Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease and multiple sclerosis.

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CitationGPTRetr519

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: it is noteworthy that to date the therapeutic potential in the treatment of neurodegenerative diseases has already been demonstrated for a number of hdac6 inhibitors in a series of preclinical studies Title of the paper: Drug pipeline in neurodegeneration based on transgenic mice models of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is one of the most important neurodegenerative disorders, bringing about huge medical and social burden in the elderly worldwide. Many aspects of its pathogenesis have remained unclear and no effective treatment exists for it. Within the past 20 years, various mice models harboring AD-related human mutations have been produced. These models imitate diverse AD-related pathologies and have been used for basic and therapeutic investigations in AD. In this regard, there are a wide variety of preclinical trials of potential therapeutic modalities using AD mice models which are of paramount importance for future clinical trials and applications. This review summarizes more than 140 substances and treatment modalities being used in transgenic AD mice models from 2001 to 2011. We also discuss advantages and disadvantages of each model to be used in therapeutic development for AD.

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CitationGPTRetr520

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The Role of P2X7 Receptor in Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by a progressive cognitive decline associated with global brain damage. Initially, intracellular paired helical filaments composed by hyperphosphorylated tau and extracellular deposits of amyloid-β (Aβ) were postulated as the causing factors of the synaptic dysfunction, neuroinflammation, oxidative stress, and neuronal death, detected in AD patients. Therefore, the vast majority of clinical trials were focused on targeting Aβ and tau directly, but no effective treatment has been reported so far. Consequently, only palliative treatments are currently available for AD patients. Over recent years, several studies have suggested the involvement of the purinergic receptor P2X7 (P2X7R), a plasma membrane ionotropic ATP-gated receptor, in the AD brain pathology. In this line, altered expression levels and function of P2X7R were found both in AD patients and AD mouse models. Consequently, genetic depletion or pharmacological inhibition of P2X7R ameliorated the hallmarks and symptoms of different AD mouse models. In this review, we provide an overview of the current knowledge about the role of the P2X7R in AD.

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CitationGPTRetr521

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: P2X7 receptor inhibition ameliorates ubiquitin-proteasome system dysfunction associated with Alzheimer's disease. Abstract of the paper: BACKGROUND Over recent years, increasing evidence suggests a causal relationship between neurofibrillary tangles (NFTs) formation, the main histopathological hallmark of tauopathies, including Alzheimer's disease (AD), and the ubiquitin-proteasome system (UPS) dysfunction detected in these patients. Nevertheless, the mechanisms underlying UPS failure and the factors involved remain poorly understood. Given that AD and tauopathies are associated with chronic neuroinflammation, here, we explore if ATP, one of the danger-associated molecules patterns (DAMPs) associated with neuroinflammation, impacts on AD-associated UPS dysfunction. METHODS To evaluate if ATP may modulate the UPS via its selective P2X7 receptor, we combined in vitro and in vivo approaches using both pharmacological and genetic tools. We analyze postmortem samples from human AD patients and P301S mice, a mouse model that mimics pathology observed in AD patients, and those from the new transgenic mouse lines generated, such as P301S mice expressing the UPS reporter UbG76V-YFP or P301S deficient of P2X7R. RESULTS We describe for the first time that extracellular ATP-induced activation of the purinergic P2X7 receptor (P2X7R) downregulates the transcription of β5 and β1 proteasomal catalytic subunits via the PI3K/Akt/GSK3/Nfr2 pathway, leading to their deficient assembly into the 20S core proteasomal complex, resulting in a reduced proteasomal chymotrypsin-like and postglutamyl-like activities. Using UPS-reported mice (UbGFP mice), we identified neurons and microglial cells as the most sensitive cell linages to a P2X7R-mediated UPS regulation. In vivo pharmacological or genetic P2X7R blockade reverted the proteasomal impairment developed by P301S mice, which mimics that were detected in AD patients. Finally, the generation of P301S;UbGFP mice allowed us to identify those hippocampal cells more sensitive to UPS impairment and demonstrate that the pharmacological or genetic blockade of P2X7R promotes their survival. CONCLUSIONS Our work demonstrates the sustained and aberrant activation of P2X7R caused by Tau-induced neuroinflammation contributes to the UPS dysfunction and subsequent neuronal death associated with AD, especially in the hippocampus.

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CitationGPTRetr522

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The P2X7 receptor: a new therapeutic target in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative illness with genetic risk as an etiological factor in a subset of cases. In AD with autosomal dominant inheritance, the extracellular β-amyloid (Aβ) aggregates and intracellular neurofibrillary tangles which consist of hyperphosphorylated tau, appear to be involved in the neuronal damage; however, other forms of AD may have a polygenetic causality. Microglial cells orchestrate pathophysiological events responsible for neuronal damage in AD. They surround Aβ aggregates and the stimulation of microglial P2X7 receptors (P2X7Rs) by high local concentrations of ATP which originates from damaged CNS cells, results in degeneration of nearby neurons. Areas covered: We discuss the pathogenesis of Alzheimer's disease, the role of P2X7 receptors and their potential as therapeutic targets. We also address the fundamental hurdles in the development of new therapeutic strategies for Alzheimer's disease. Expert opinion: There are many difficulties associated with the development of efficient pharmacological strategies for AD; the lack of good animal and cellular models for this illness is a key obstacle. None of the pharmacological strategies developed so far have led to an improvement of the treatment of AD. Hence, the consideration of blood-brain barrier-permeable P2X7R antagonists as possible therapeutic agents in AD is a must.

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CitationGPTRetr523

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: P2X7 receptor signaling pathway as a therapeutic target for neurodegenerative diseases. Abstract of the paper: A recent study suggested that neuroinflammation plays a major role in the pathogenesis of a number of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Although the precise mechanism is obscure, dysregulation of the signaling transduction pathway in microglia may enhance inflammation, leading to synaptic dysfunction and ultimately to neuronal cell death. The expression and function of the P2X7 receptor (P2X7R), an ATP-gated ion channel abundantly expressed in microglia in the brain, is significantly up-regulated in the postmortem brain of Alzheimer's disease patients and various neurodegenerative disease animal models. This supports the role of the P2X7R pathway in the progression of neurodegeneration. Blocking P2X7R using brilliant blue G, a P2X7R antagonist that can cross the blood-brain barrier, has been shown to result in the amelioration of neuropathology in various animal models. Taken together, these results raise the possibility that the P2X7R signaling pathway could be a therapeutic target for treating various neurodegenerative diseases.

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CitationGPTRetr524

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The role of P2X7R in neuroinflammation and implications in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of dementia and is set to rise in prevalence as the global trends in population aging. The extracellular deposition of amyloid protein (Aβ) and the intracellular formation of neurofibrillary tangles in the brain have been recognized as the two core pathologies of AD. Over the past decades, the presence of neuroinflammation in the brain has been documented as the third core pathology of AD. In recent years, emerging evidence demonstrated that the purinergic receptor P2X7 (P2X7R) serves a critical role in microglia responses and neuroinflammation. Besides, targeting P2X7R by genetic or pharmacological strategies attenuates the symptoms and pathological changes of AD models, and P2X7R has been recognized as a promising therapeutic target for AD. In this review, we summarized the recent evidence concerning the roles of P2X7R in neuroinflammation and implications in AD pathogenesis.

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CitationGPTRetr525

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: P2X7 Receptors in Neurodegeneration: Potential Therapeutic Applications From Basic to Clinical Approaches. Abstract of the paper: Purinergic receptors play important roles in central nervous system (CNS), where the bulk of these receptors are implicated in neuroinflammatory responses and regulation of cellular function of neurons, microglial and astrocytes. Within the P2X receptor family, P2X7 receptor is generally known for its inactivity in normal conditions and activation by moderately high concentrations (>100 μM) of extracellular adenosine 5'-triphosphate (ATP) released from injured cells as a result of brain injury or pathological conditions. Activation of P2X7R contributes to the activation and proliferation of microglia and directly contribute to neurodegeneration by provoking microglia-mediated neuronal death, glutamate-mediated excitotoxicity, and NLRP3 inflammasome activation that results in initiation, maturity and release of the pro-inflammatory cytokines and generation of reactive oxygen and nitrogen species. These components of the inflammatory response play important roles in many neural pathologies and neurodegeneration disorders. In CNS, expression of P2X7R on microglia, astrocytes, and oligodendrocytes are upregulated under neuroinflammatory conditions. Several in vivo studies have demonstrated beneficial effects of the P2X7 receptor antagonists in animal model systems of neurodegenerative diseases. A number of specific and selective P2X7 receptor antagonists have been developed, but only few of them have shown efficient brain permeability. Finding potent and selective P2X7 receptor inhibitors which are also CNS penetrable and display acceptable pharmacokinetics (PK) has presented challenges for both academic researchers and pharmaceutical companies. In this review, we discuss the role of P2X7 receptor function in neurodegenerative diseases, the pharmacological inhibition of the receptor, and PET radiopharmaceuticals which permit non-invasive monitoring of the P2X7 receptor contribution to neuroinflammation associated with neurodegeneration.

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CitationGPTRetr526

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The ubiquitin-proteasome system in neurodegeneration. Abstract of the paper: SIGNIFICANCE Impairment of the ubiquitin-proteasome system (UPS) has been implicated in the pathogenesis of a wide variety of neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases. The most significant risk factor for the development of these disorders is aging, which is associated with a progressive decline in UPS activity and the accumulation of oxidatively modified proteins. To date, no therapies have been developed that can specifically up-regulate this system. RECENT ADVANCES In the neurodegenerative brain, dysfunction of the UPS has been associated with the deposition of ubiquitinated protein aggregates and widespread disruption of the proteostasis network. Recent research has identified further evidence of impairment in substrate ubiquitination and proteasomal degradation, which could contribute to the loss of cellular proteostasis in neurodegenerative disease. Novel strategies for activation of the UPS by genetic manipulation and treatment with synthetic compounds have also recently been identified. CRITICAL ISSUES Here, we discuss the specific roles of the UPS in the healthy central nervous system and establish how dysfunctional components can contribute to neurotoxicity in the context of disease. FUTURE DIRECTIONS Knowledge of the UPS components that are specifically or preferentially involved in neurodegenerative disease will be critical in the development of targeted therapies which aim at limiting the accumulation of misfolded proteins without gross disturbance of this major proteolytic pathway.

False

CitationGPTRetr527

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases. Abstract of the paper: Neurodegenerative diseases (NDDs) represent a huge social burden, particularly in Alzheimer's disease (AD) in which all proposed treatments investigated in murine models have failed during clinical trials (CTs). Thus, novel therapeutic strategies remain crucial. Neuroinflammation is a common pathogenic feature of NDDs. As purinergic P2X7 receptors (P2X7Rs) are gatekeepers of inflammation, they could be developed as drug targets for NDDs. Herein, we review this challenging hypothesis and comment on the numerous studies that have investigated P2X7Rs, emphasizing their molecular structure and functions, as well as their role in inflammation. Then, we elaborate on research undertaken in the field of medicinal chemistry to determine potential P2X7R antagonists. Subsequently, we review the state of neuroinflammation and P2X7R expression in the brain, in animal models and patients suffering from AD, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and retinal degeneration. Next, we summarize the in vivo studies testing the hypothesis that by mitigating neuroinflammation, P2X7R blockers afford neuroprotection, increasing neuroplasticity and neuronal repair in animal models of NDDs. Finally, we reviewed previous and ongoing CTs investigating compounds directed toward targets associated with NDDs; we propose that CTs with P2X7R antagonists should be initiated. Despite the high expectations for putative P2X7Rs antagonists in various central nervous system diseases, the field is moving forward at a relatively slow pace, presumably due to the complexity of P2X7Rs. A better pharmacological approach to combat NDDs would be a dual strategy, combining P2X7R antagonism with drugs targeting a selective pathway in a given NDD.

False

CitationGPTRetr528

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: Molecular Insight into the Crosstalk of UPS Components and Alzheimer's Disease. Abstract of the paper: The ubiquitin (Ub)-proteasome system (UPS) targets various cellular proteins for degradation. It has been found that defects in the UPS play a crucial role in the pathogenesis of Alzheimer's disease (AD), as the existence of Ub immunoreactivity in AD-linked neuronal inclusions, including neurofibrillary tangles, is observed in all types of AD cases. Current investigations have shown that components of the UPS can be connected with the early stage of AD, which is characterized by synaptic dysfunction, and to the late phases of the disease, marked by neurodegeneration. Although the significance of UPS in the pathogenesis of AD has been emphasized, targeted treatment at the main components of these pathways has a great perspective in advancing new therapeutic interventions for AD. In this review, we emphasize the relationship between UPS and AD pathology. We also represent the recent therapeutic advancements targeting UPS components in AD.

False

CitationGPTRetr529

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: Emerging role of P2X7 receptors in CNS health and disease. Abstract of the paper: Purinergic signalling in the brain is becoming an important focus in the study of CNS health and disease. Various purinergic receptors are found to be present in different brain cells in varying extent, which get activated upon binding of ATP or its analogues. Conventionally, ATP was considered only as a major metabolic fuel of the cell but its recognition as a neurotransmitter in early 1970s, brought meaningful insights in neuron glia crosstalk, participating in various physiological functions in the brain. P2X7R, a member of ligand gated purinergic receptor (P2X) family, is gaining attention in the field of neuroscience because of its emerging role in broad spectrum of ageing and age related neurological disorders. The aim of this review is to provide an overview about the structure and function of P2X7R highlighting its unique features which distinguish it from the other members of its family. This review critically analyzes the literature mentioning the details about the agonist and antagonist of the P2X7R. It also emphasizes the advancements in understanding the dual role of P2X7R in brain development and disorders inviting meaningful insights about its involvement in Alzheimer's disease, Huntington's disease, Multiple Sclerosis, Neuropathic pain, Spinal Cord Injury and NeuroAIDS. Exploring the roles of P2X7R in detail is critical to identify its therapeutic potential in the treatment of acute and chronic neurodegenerative diseases. Moreover, this review also helps to raise more interest in the neurobiology of the purinergic receptors and thus providing new avenues for future research.

False

CitationGPTRetr530

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: Protein ubiquitination, degradation and the proteasome in neuro-degenerative disorders: no clear evidence for a significant pathogenetic role of proteasome failure in Alzheimer disease and related disorders. Abstract of the paper: It has recently been proposed that Alzheimer disease (AD) might be initiated by a molecular 'hit' into a regulatory protein, e.g. a cell surface receptor [Schmitt HP. Neuro-modulation, aminergic neuro-disinhibition and neuro-degeneration: draft of a comprehensive theory for Alzheimer disease. Med Hypoth 2005;65:1106-19]. However, other substrates, in particular intra-cellular protein complexes such as the ubiquitin/proteasome system (UPS) could as well serve as a targets for such a 'hit' which might insert a mutation or induce conformational changes resulting in functional failure of protein degradation along the ubiquitin/proteasome proteolytic pathway. It has been claimed that impairment of the large multi-catalytic protease complex, the 20S/26S proteasome, might represent a key factor in the early pathogenesis of neuro-degenerative disorders characterized by the formation of abnormal protein aggregates such as neuronal cytoplasmic or nuclear inclusion bodies and fibrillary deposits. This article aims to review critically whether current information really supports the idea that impairment of the UPS might play a significant role in the early pathogenesis of neuro-degenerative disorders, with special emphasis on AD. The data provided in favour of proteasome impairment were, as a rule, revealed in in vitro experiments which cannot be unequivocally transferred to the in vivo conditions in neuro-degeneration. The author concludes that there is yet no clear evidence of a pivotal role of proteasome failure in the early pathogenesis of AD.

False

CitationGPTRetr531

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The ubiquitin proteasome system as a potential target for the treatment of neurodegenerative diseases. Abstract of the paper: Neurodegenerative diseases are severe disorders characterized by progressive neurodegeneration in specific brain regions. The ubiquitin-proteasome system (UPS) is closely linked to neurodegenerative disease. In most cases, UPS impairment and dysregulation of the UPS components are frequently observed. Moreover, toxin-induced neurodegeneration produces neuronal cell death accompanied by decreased UPS function. These studies suggest an involvement of the UPS in these diseases. In this review, we summarize the changes to UPS components in neurodegenerative diseases and the association between the UPS and disease pathology. Dysfunction of the UPS results in the abnormal accumulation of proteins; thus, the UPS plays a critical role in disease pathogenesis. Drugs targeting specific components of the UPS may provide promising strategies for disease treatment.

False

CitationGPTRetr532

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The ubiquitin-proteasome system in Alzheimer's disease. Abstract of the paper: Accumulation of proteins is a recurring event in many neurodegenerative diseases, including Alzheimer's disease (AD). Evidence has suggested that protein accumulation may result from a dysfunction in the ubiquitin proteasome system (UPS). Indeed, there is clear genetic and biochemical evidence of an involvement of the ubiquitin proteasome system in AD. This review summarizes the data supporting an involvement of the UPS in the pathogenesis of AD, focusing on the data showing the relationship between Abeta and tau, the two hallmark lesions of AD, and the UPS.

True

CitationGPTRetr533

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: Exploring the Promise of Targeting Ubiquitin-Proteasome System to Combat Alzheimer's Disease. Abstract of the paper: The ubiquitin (Ub)-proteasome system (UPS) is considered as a central protein degradation system in all eukaryotes. The UPS comprises of several factors such as Ub and Ub-like molecules, Ub hydrolases, E3 Ub ligases, and the proteasome itself. Numerous studies have demonstrated that the dysfunction of UPS plays an essential role in the pathogenesis and progression of Alzheimer's disease (AD). Furthermore, current evidence has suggested that the UPS components can be connected with the initial stage of AD that is characterized by synaptic dysfunction, and to the late phases of AD, marked by neurodegeneration. In AD patients, the accumulations of insoluble protein in the brain can be caused by overload or dysfunction of the UPS, or by conformational alterations in the protein substrates that prevent their degradation and recognition by the UPS. Synaptic dysfunction is also caused by defective proteolysis that has found in the initial stage in AD as the UPS is widely recognized to play a pivotal role in the regular activities of synapses. Conversely, its precise cause and pathogenesis are unclear. Presently accepted medicines for AD give symptomatic relief, though they are unable to stop the progression of the disease. Besides, the components of the cellular quality control system demonstrate a significant emphasis on the advancement of targeted and effective treatments for AD. In this review, we focus on the role of UPS in the pathogenesis of AD and highlight how the UPS-linked treatments influence in the management of AD.

False

CitationGPTRetr534

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution. Abstract of the paper: The ubiquitin-proteasome system (UPS) has been implicated in neurodegenerative diseases based on the presence of deposits consisting of ubiquitylated proteins in affected neurons. It has been postulated that aggregation-prone proteins associated with these disorders, such as α-synuclein, β-amyloid peptide, and polyglutamine proteins, compromise UPS function, and delay the degradation of other proteasome substrates. Many of these substrates play important regulatory roles in signaling, cell cycle progression, or apoptosis, and their inadvertent stabilization due to an overloaded and improperly functioning UPS may thus be responsible for cellular demise in neurodegeneration. Over the past decade, numerous studies have addressed the UPS dysfunction hypothesis using various model systems and techniques that differ in their readout and sensitivity. While an inhibitory effect of some disease proteins on the UPS has been demonstrated, increasing evidence attests that the UPS remains operative in many disease models, which opens new possibilities for treatment. In this review, we will discuss the paradigm shift that repositioned the UPS from being a prime suspect in the pathophysiology of neurodegeneration to an attractive therapeutic target that can be harnessed to accelerate the clearance of disease-linked proteins.

False

CitationGPTRetr535

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: Role of the ubiquitin proteasome system in Alzheimer's disease. Abstract of the paper: Though Alzheimer's disease (AD) is a syndrome with well-defined clinical and neuropathological manifestations, an array of molecular defects underlies its pathology. A role for the ubiquitin proteasome system (UPS) was suspected in the pathogenesis of AD since the presence of ubiquitin immunoreactivity in AD-related neuronal inclusions, such as neurofibrillary tangles, is seen in all AD cases. Recent studies have indicated that components of the UPS could be linked to the early phase of AD, which is marked by synaptic dysfunction, as well as to the late stages of the disease, characterized by neurodegeneration. Insoluble protein aggregates in the brain of AD patients could result from malfunction or overload of the UPS, or from structural changes in the protein substrates, which prevent their recognition and degradation by the UPS. Defective proteolysis could cause the synaptic dysfunction observed early in AD since the UPS is known to play a role in the normal functioning of synapses. In this review, we discuss recent observations on possible links between the UPS and AD, and the potential for utilizing UPS components as targets for treatment of this disease. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).

False

CitationGPTRetr536

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim? Abstract of the paper: A shared hallmark for many neurodegenerative disorders is the accumulation of toxic protein species which is assumed to be the cause for these diseases. Since the ubiquitin proteasome system (UPS) is the most important pathway for selective protein degradation it is likely that it is involved in the aetiology neurodegenerative disorders. Indeed, impairment of the UPS has been reported to occur during neurodegeneration. Although accumulation of toxic protein species (amyloid β) are in turn known to impair the UPS the relationship is not necessarily causal. We provide an overview of the most recent insights in the roles the UPS plays in protein degradation and other processes. Additionally, we discuss the role of the UPS in clearance of the toxic proteins known to accumulate in the hallmarks of neurodegenerative diseases. The present paper will focus on critically reviewing the involvement of the UPS in specific neurodegenerative diseases and will discuss if UPS impairment is a cause, a consequence or both of the disease.

False

CitationGPTRetr537

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases. Abstract of the paper: ATP is a (co)transmitter and signaling molecule in the CNS. It acts at a multitude of ligand-gated cationic channels termed P2X to induce rapid depolarization of the cell membrane. Within this receptor-channel family, the P2X7 receptor (R) allows the transmembrane fluxes of Na+, Ca2+, and K+, but also allows the slow permeation of larger organic molecules. This is supposed to cause necrosis by excessive Ca2+ influx, as well as depletion of intracellular ions and metabolites. Cell death may also occur by apoptosis due to the activation of the caspase enzymatic cascade. Because P2X7Rs are localized in the CNS preferentially on microglia, but also at a lower density on neuroglia (astrocytes, oligodendrocytes) the stimulation of this receptor leads to the release of neurodegeneration-inducing bioactive molecules such as pro-inflammatory cytokines, chemokines, proteases, reactive oxygen and nitrogen molecules, and the excitotoxic glutamate/ATP. Various neurodegenerative reactions of the brain/spinal cord following acute harmful events (mechanical CNS damage, ischemia, status epilepticus) or chronic neurodegenerative diseases (neuropathic pain, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis) lead to a massive release of ATP via the leaky plasma membrane of neural tissue. This causes cellular damage superimposed on the original consequences of neurodegeneration. Hence, blood-brain-barrier permeable pharmacological antagonists of P2X7Rs with excellent bioavailability are possible therapeutic agents for these diseases. The aim of this review article is to summarize our present state of knowledge on the involvement of P2X7R-mediated events in neurodegenerative illnesses endangering especially the life quality and duration of the aged human population.

False

CitationGPTRetr538

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: P2X7-deficiency improves plasticity and cognitive abilities in a mouse model of Tauopathy. Abstract of the paper: Alzheimer's disease is the most common form of dementia characterized by intracellular aggregates of hyperphosphorylated Tau protein and extracellular accumulation of amyloid β (Aβ) peptides. We previously demonstrated that the purinergic receptor P2X7 (P2X7) plays a major role in Aβ-mediated neurodegeneration but the relationship between P2X7 and Tau remained overlooked. Such a link was supported by cortical upregulation of P2X7 in patients with various type of frontotemporal lobar degeneration, including mutation in the Tau-coding gene, MAPT, as well as in the brain of a Tauopathy mouse model (THY-Tau22). Subsequent phenotype analysis of P2X7-deficient Tau mice revealed the instrumental impact of this purinergic receptor. Indeed, while P2X7-deficiency had a moderate effect on Tau pathology itself, we observed a significant reduction of microglia activation and of Tau-related inflammatory mediators, particularly CCL4. Importantly, P2X7 deletion ultimately rescued synaptic plasticity and memory impairments of Tau mice. Altogether, the present data support a contributory role of P2X7 dysregulation on processes governing Tau-induced brain anomalies. Due to the convergent role of P2X7 blockade in both Aβ and Tau background, P2X7 inhibitors might prove to be ideal candidate drugs to curb the devastating cognitive decline in Alzheimer's disease and Tauopathies.

True

CitationGPTRetr539

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: since ups impairment has been recognized as the hallmark of a wide range of neurodegenerative disorders including ad 14 43 a disease in which patients show higher p2x7r expression levels we wonder whether increased p2x7r signaling may contribute to the adassociated ups impairment Title of the paper: The role of the ubiquitin proteasome system in Alzheimer's disease. Abstract of the paper: Today, Alzheimer's disease (AD) is one of the most important age-related neurodegenerative diseases, but its etiology remains still unknown. Since the discovery that the hallmark structures of this disease i.e. the formation of amyloid fibers could be the product of ubiquitin-mediated protein degradation defects, it has become clear that the ubiquitin-proteasome system (UPS), usually essential for protein repair, turnover and degradation, is perturbed in this disease. Different aspects of normal and pathological aging are discussed with respect to protein repair and degradation via the UPS, as well as consequences of a deficit in the UPS in AD. Selective protein oxidation may cause protein damage, or protein mutations may induce a dysfunction of the proteasome. Such events eventually lead to activation of cell death pathways and to an aberrant aggregation or incorporation of ubiquitinated proteins into hallmark structures. Aggresome formation is also observed in other neurodegenerative diseases, suggesting that an activation of similar mechanisms must occur in neurodegeneration as a basic phenomenon. It is essential to discuss therapeutic ways to investigate the UPS dysfunction in the human brain and to identify specific targets to hold or stop cell decay.

False

CitationGPTRetr540

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Comprehension of concrete and abstract words in semantic dementia. Abstract of the paper: The vast majority of brain-injured patients with semantic impairment have better comprehension of concrete than abstract words. In contrast, several patients with semantic dementia (SD), who show circumscribed atrophy of the anterior temporal lobes bilaterally, have been reported to show reverse imageability effects, that is, relative preservation of abstract knowledge. Although these reports largely concern individual patients, some researchers have recently proposed that superior comprehension of abstract concepts is a characteristic feature of SD. This would imply that the anterior temporal lobes are particularly crucial for processing sensory aspects of semantic knowledge, which are associated with concrete not abstract concepts. However, functional neuroimaging studies of healthy participants do not unequivocally predict reverse imageability effects in SD because the temporal poles sometimes show greater activation for more abstract concepts. The authors examined a case-series of 11 SD patients on a synonym judgment test that orthogonally varied the frequency and imageability of the items. All patients had higher success rates for more imageable as well as more frequent words, suggesting that (1) the anterior temporal lobes underpin semantic knowledge for both concrete and abstract concepts, (2) more imageable items--perhaps because of their richer multimodal representations--are typically more robust in the face of global semantic degradation and (3) reverse imageability effects are not a characteristic feature of SD.

True

CitationGPTRetr541

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Semantic memory in Alzheimer's disease and the frontotemporal dementias: a longitudinal study of 236 patients. Abstract of the paper: Using semantic dementia (SD) as a reference point, the authors assessed semantic memory in four other neurodegenerative disorders: progressive nonfluent aphasia (PNFA), frontal variant frontotemporal dementia (fvFTD), Alzheimer's disease (AD), and posterior cortical atrophy (PCA). Individuals with SD were more impaired than other groups on semantic measures and showed a characteristic pattern across tasks: category fluency (CF) worse than letter fluency (LF), naming worse than comprehension, and visual and verbal comprehension equally affected, suggesting disruption to an amodal semantic system. Individuals with AD demonstrated a similar pattern to a milder degree. Although PNFA, fvFTD, and PCA groups had abnormal scores (relative to controls) on most semantic measures, their differing patterns across measures indicate that the apparent semantic impairment in these conditions is largely secondary to other factors.

False

CitationGPTRetr542

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Abstract and concrete categories? Evidences from neurodegenerative diseases. Abstract of the paper: We assessed the performance of patients with a diagnosis of Alzheimer׳s disease (AD) and of the semantic variant of primary progressive aphasia (sv-PPA) in a series of tasks involving both abstract and concrete stimuli, which were controlled for most of the variables that have been shown to affect performance on lexical-semantic tasks. Our aims were to compare the patients׳ performance on abstract and concrete stimuli and to assess category-effects within the abstract and concrete domains. The results showed: (i) a better performance on abstract than concrete concepts in sv-PPA patients. (ii) Category-related effects in the abstract domain, with emotion concepts being preserved in AD and social relations being selectively impaired in sv-PPA. In addition, a living-non living dissociation may be (infrequently) observed in individual AD patients after controlling for an extensive set of potential confounds. Thus, differences between and within the concrete or abstract domain may be present in patients with semantic memory disorders, mirroring the different brain regions involved by the different pathologies.

False

CitationGPTRetr543

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Category and letter fluency in semantic dementia, primary progressive aphasia, and Alzheimer's disease. Abstract of the paper: This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive aphasia, and Alzheimer's disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical frequency and errors recorded. The findings are consistent with the view that category and letter fluency rely on both common and unique cognitive processes. Fluency tasks, with the richness of data obtained, are valuable in distinguishing different dementia syndromes from one another.

False

CitationGPTRetr544

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Different types of abstract concepts: evidence from two neurodegenerative patients. Abstract of the paper: The observation of neurological patients showing selective impairments for specific conceptual categories contributed in the development of semantic memory theories. Here, we studied two patients (P01, P02), affected, respectively, by the semantic variant of Primary Progressive Aphasia (sv-PPA) and Cortico-Basal Syndrome (CBS). An implicit lexical decision task, including concrete (animals, tools) and abstract (emotions, social, quantity) concepts, was administered to patients and healthy controls.P01 and P02 showed an abolished priming effect for social and quantity-related concepts, respectively. This double dissociation suggests a role of different brain areas in representing specific abstract categories, giving insights for current semantic memory theories.

True

CitationGPTRetr545

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Reverse concreteness effects are not a typical feature of semantic dementia: evidence for the hub-and-spoke model of conceptual representation. Abstract of the paper: The role of anterior temporal lobes (ATLs) in semantic processing is controversial. One theory, influenced by semantic dementia (SD) patients, is that this region is a pan-modal hub for all concepts. An alternative view is that atrophy in SD specifically affects knowledge for visual features. This is supported by reports of reverse concreteness effects in a few SD patients, suggesting that abstract word knowledge is spared relative to concrete words. However, it is not clear whether such effects are typical in SD, hence reliably associated with ATL damage, because most reports are of single cases and group studies have produced conflicting results. To address these contradictions, we investigated concreteness effects in 7 SD patients, using multiple tests from earlier studies in addition to new assessments. Comprehension was impaired for both word types but was better for concrete words. However, this pattern was not found uniformly across all tests and was most likely to be observed when: 1) concrete and abstract words were well matched for word frequency and 2) concrete and abstract words were selected with sufficient variation along the imageability scale. These factors account for the variability in previous studies and indicate that reverse concreteness effects are not common in SD.

True

CitationGPTRetr546

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Semantic profiles in mild cognitive impairment associated with Alzheimer's and Parkinson's diseases. Abstract of the paper: The temporal and the prefrontal cortices have different roles in semantic information processing: the temporal lobe is where knowledge is stored (Graham and Hodges, 1997), whereas the prefrontal cortex is more specifically involved in executive aspects of semantic processing. Relatively little is known about the semantic profiles of mild cognitive impairment (MCI) in Alzheimer's disease (AD) and Parkinson's disease (PD). This observational study investigated naming and semantic questionnaire performances in three groups of subjects: 10 patients with the amnestic-type MCI prodrome of AD (aMCI), 10 patients with early-stage executive-type MCI in PD (MCI-PD), and 10 normal subjects. The MCI-PD subjects demonstrated inferior performances on a semantic questionnaire, whereas the aMCI group displayed modest difficulties in a naming task. These differences may be explained by topographical differences in pathological involvement. Since the frontal areas are more functionally impaired in PD, we hypothesize that the semantic deficit may be a consequence of a deficiency in control of semantic processing. On the other hand, the semantic deficit in aMCI may be related to a lexical-semantic storage dysfunction resulting from pathological involvement of the temporal lobe.

False

CitationGPTRetr547

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Be concrete to be comprehended: consistent imageability effects in semantic dementia for nouns, verbs, synonyms and associates. Abstract of the paper: There are two contrasting views on the nature of comprehension impairment in semantic dementia: (a) that it stems from degradation of a pan-modal "hub" that represents core conceptual knowledge or (b) that it results from degradation of modality-specific visual feature knowledge. These theories make divergent predictions regarding comprehension of concrete versus abstract words in the disorder. The visual hypothesis predicts that concrete words should be particularly impaired because they depend heavily on visual information. In contrast, the pan-modal hub hypothesis holds that all types of knowledge are affected but predicts less severe impairment of concrete words because they have richer and more detailed semantic representations than abstract words. We investigated concreteness effects in the comprehension of six SD patients. Across nouns, verbs, synonymous and associative relationships, a clear and consistent pattern emerged: concrete words were always comprehended more successfully than abstract words. These findings extend those of previous studies and suggest that conceptual impairment in SD is not confined to concepts that rely on visual information. Instead, all types of knowledge are affected by the progressive deterioration of modality-invariant representations (required for coherent pan-modal concepts). Concrete words succumb less quickly by virtue of their richer and more detailed semantic representations.

True

CitationGPTRetr548

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Reversal of the concreteness effect in semantic dementia. Abstract of the paper: Patients with semantic dementia (SD) have a striking impairment in semantic memory, but the basis for this deficit is unclear. We examined semantic memory for concrete and abstract verbs with a two-alternative, forced-choice measure of lexical semantic associative knowledge. Patients with SD had significantly greater difficulty with concrete verbs (z = -3.33) than with abstract verbs (z = -2.05), a "reversal of the concreteness effect" that was present in a majority of individual patients. The subgroup of SD patients with imaging had significant cortical thinning in the anterior and inferolateral portions of the temporal lobes. These areas of visual association cortex may be important for storing and processing visual features for word meaning. Moreover, poor performance with concrete relative to abstract verbs correlated with cortical thinning of the right anterior temporal lobe in SD, suggesting that this region may contribute to storing and processing visual semantic features. These observations raise the possibility that degraded visual feature knowledge contributes in part to the impaired comprehension of concrete words in SD.

False

CitationGPTRetr549

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Partial knowledge of abstract words in patients with cortical degenerative conditions. Abstract of the paper: Partial knowledge is a common but rarely studied consequence of damage to conceptual representations and is characterized by the retained ability to retrieve crude, superordinate information but not specific, detailed information about a conceptual entity. Previous studies have described partial knowledge for concrete items particularly following semantic dementia (SD). The present study was designed to investigate the occurrence of partial knowledge effects in the conceptual domain of abstract words. A novel 3-level synonym comprehension test was administered to 9 patients with SD, 20 patients with probable Alzheimer's disease (AD), and 40 healthy control subjects. All subject groups showed weaker performance on tasks requiring a fine specification of word meaning compared with those for which a broad sense of meaning or valence was necessary. However, this gradient of partial knowledge was significantly greater for SD and AD subjects than for controls. These results demonstrate that partial knowledge is a general property of a degraded knowledge base and is not restricted to the concrete word domain. It constitutes a normal phenomenon that is exacerbated in the context of neurodegenerative disease.

False

CitationGPTRetr550

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study. Abstract of the paper: The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions.

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CitationGPTRetr551

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Reversal of the concreteness effect for verbs in patients with semantic dementia. Abstract of the paper: The authors assessed comprehension of carefully matched classes of words, manipulating grammatical subcategory (noun and verb) and semantic (concrete and abstract) characteristics for participants with semantic dementia (SD) or probable Alzheimer's disease (AD). Participants selected the best of four words that matched a verbal description. Participants with AD or SD were significantly impaired with verbs compared with nouns. Moreover, participants with SD showed significantly greater difficulty with motion verbs compared to cognition verbs. The authors argue that two factors contribute to the difficulty with motion verbs for patients with SD. First, the verb semantic network is very poorly organized relative to the noun semantic network, leaving verbs more vulnerable to a progressive neurodegenerative disease. Second, visual feature knowledge is degraded in patients with SD because of the anatomic distribution of the disease in visual association cortex, causing relatively greater difficulty for concrete verbs compared to abstract verbs.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Disorders of representation and control in semantic cognition: Effects of familiarity, typicality, and specificity. Abstract of the paper: We present a case-series comparison of patients with cross-modal semantic impairments consequent on either (a) bilateral anterior temporal lobe atrophy in semantic dementia (SD) or (b) left-hemisphere fronto-parietal and/or posterior temporal stroke in semantic aphasia (SA). Both groups were assessed on a new test battery designed to measure how performance is influenced by concept familiarity, typicality and specificity. In line with previous findings, performance in SD was strongly modulated by all of these factors, with better performance for more familiar items (regardless of typicality), for more typical items (regardless of familiarity) and for tasks that did not require very specific classification, consistent with the gradual degradation of conceptual knowledge in SD. The SA group showed significant impairments on all tasks but their sensitivity to familiarity, typicality and specificity was more variable and governed by task-specific effects of these factors on controlled semantic processing. The results are discussed with reference to theories about the complementary roles of representation and manipulation of semantic knowledge.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Effects of semantic impairment on language use in Alzheimer's disease. Abstract of the paper: Many studies present apparently conflicting results and conclusions about the effects of Alzheimer's disease (AD) on language use. This review attempts to reconcile these apparently conflicting results regarding the language impairments in AD by discussing how the slow deterioration of the semantic system at the feature level interacts with the task demands of tests used to evaluate performance. In particular, performance is impaired on tasks that require relatively complete, elaborate semantic representations but is preserved when the task requires only partial semantic representations consisting largely of shared features. The variety of language impairments reported in complex, multiword tasks are likely attributable to a combination of the deterioration of semantic representations and reduced working memory resources. The few available treatment studies for language impairments in AD suggest that treatments designed for adults with other language impairments, such as aphasia, may also be effective in AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Semantic memory in Alzheimer's disease. Abstract of the paper: Patients with Alzheimer's disease have been suggested to have a semantic memory impairment not present in the normal old. This article reviews the performance of Alzheimer patients on tests of various aspects of semantic memory, including word finding, knowledge of the semantic attributes, and associates of concepts, as well as their category membership. The effect that semantic context has on cognitive processes such as lexical and semantic priming and memory encoding is also reviewed. Finally, the ability of theoretical constructs such as implicit memory and automaticity to explain intertask variability in Alzheimer patients' semantic performance is discussed.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Non-verbal semantic impairment in semantic dementia. Abstract of the paper: The clinical presentation of patients with semantic dementia is dominated by anomia and poor verbal comprehension. Although a number of researchers have argued that these patients have impaired comprehension of non-verbal as well as verbal stimuli, the evidence for semantic deterioration is mainly derived from tasks that include some form of verbal input or output. Few studies have investigated semantic impairment using entirely non-verbal assessments and the few exceptions have been based on results from single cases ([3]: Breedin SD, Saffran EM, Coslett HB. Reversal of the concreteness effect in a patient with semantic dementia. Cognitive Neuropsychology 1994;11:617-660, [12]: Graham KS, Becker JT, Patterson K, Hodges JR. Lost for words: a case of primary progressive aphasia? In: Parkin A, editor. Case studies in the neuropsychology of memory, East Sussex: Lawrence Erlbaum, 1997. pp. 83-110, [21]: Lambon Ralph MA, Howard D. Gogi aphasia or semantic dementia? Simulating and assessing poor verbal comprehension in a case of progressive fluent aphasia. Cognitive Neuropsychology, (in-press). This study employed sound recognition and semantic association tasks to investigate the nature of the verbal and non-verbal comprehension deficit in 10 patients with semantic dementia. The patients were impaired on both verbal and non-verbal conditions of the assessments, and their accuracy on these tasks was directly related to their scores on a range of other tests requiring access to semantic memory. Further analyses revealed that performance was graded by concept and sound familiarity and, in addition, identified significant item consistency across the different conditions of the tasks. These results support the notion that the patients' deficits across all modalities were due to degradation within a single, central network of conceptual knowledge. There were also reliable differences between conditions. The sound-picture matching task proved to be more sensitive to semantic impairment than the word-picture matching equivalent, and the patients performed significantly better on the picture than word version of a semantic association test. We propose that these differences arise directly from the nature of the mapping between input modality and semantic memory. Words and sounds have an arbitrary relationship with meaning while pictures benefit from a degree of systematicity with conceptual knowledge about the object.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease. Abstract of the paper: The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: Patterns of semantic memory impairment in Mild Cognitive Impairment. Abstract of the paper: Although the semantic memory impairment has been largely documented in Alzheimer's disease, little is known about semantic memory in the preclinical phase of the disease (Mild Cognitive Impairment). The purpose of this study was to document the nature of semantic breakdown using a battery of tests assessing different aspects of conceptual knowledge: knowledge about common objects, famous people and famous public events. Results indicate that all domains of semantic memory were impaired in MCI individuals but knowledge about famous people and famous events was affected to a greater extent than knowledge about objects. This pattern of results suggests that conceptual entities with distinctive and unique properties may be more prone to semantic breakdown in MCI. In summary, results of this study support the view that genuine semantic deficits are present in MCI. It could be useful to investigate the etiological outcome of patients failing or succeeding at such tests.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: The meaning of 'life' and other abstract words: Insights from neuropsychology. Abstract of the paper: There are a number of long-standing theories on how the cognitive processing of abstract words, like 'life', differs from that of concrete words, like 'knife'. This review considers current perspectives on this debate, focusing particularly on insights obtained from patients with language disorders and integrating these with evidence from functional neuroimaging studies. The evidence supports three distinct and mutually compatible hypotheses. (1) Concrete and abstract words differ in their representational substrates, with concrete words depending particularly on sensory experiences and abstract words on linguistic, emotional, and magnitude-based information. Differential dependence on visual versus verbal experience is supported by the evidence for graded specialization in the anterior temporal lobes for concrete versus abstract words. In addition, concrete words have richer representations, in line with better processing of these words in most aphasic patients and, in particular, patients with semantic dementia. (2) Abstract words place greater demands on executive regulation processes because they have variable meanings that change with context. This theory explains abstract word impairments in patients with semantic-executive deficits and is supported by neuroimaging studies showing greater response to abstract words in inferior prefrontal cortex. (3) The relationships between concrete words are governed primarily by conceptual similarity, while those of abstract words depend on association to a greater degree. This theory, based primarily on interference and priming effects in aphasic patients, is the most recent to emerge and the least well understood. I present analyses indicating that patterns of lexical co-occurrence may be important in understanding these effects.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: six studies 25 99 patients found better performance with concrete compared to abstract concepts Title of the paper: A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment. Abstract of the paper: Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. 22 studies (476 healthy participants, 476 MCI patients, mean Mini Mental Status Examination of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy in Alzheimer's Disease and Other Age-Related Neurodegenerative Diseases. Abstract of the paper: Mitochondrial dysfunction is a central aspect of aging and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Mitochondria are the main cellular energy powerhouses, supplying most of ATP by oxidative phosphorylation, which is required to fuel essential neuronal functions. Efficient removal of aged and dysfunctional mitochondria through mitophagy, a cargo-selective autophagy, is crucial for mitochondrial maintenance and neuronal health. Mechanistic studies into mitophagy have highlighted an integrated and elaborate cellular network that can regulate mitochondrial turnover. In this review, we provide an updated overview of the recent discoveries and advancements on the mitophagy pathways and discuss the molecular mechanisms underlying mitophagy defects in Alzheimer's disease and other age-related neurodegenerative diseases, as well as the therapeutic potential of mitophagy-enhancing strategies to combat these disorders.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Targeting Mitophagy in Alzheimer's Disease. Abstract of the paper: Mitochondria perform many essential cellular functions including energy production, calcium homeostasis, transduction of metabolic and stress signals, and mediating cell survival and death. Maintaining viable populations of mitochondria is therefore critical for normal cell function. The selective disposal of damaged mitochondria, by a pathway known as mitophagy, plays a key role in preserving mitochondrial integrity and quality. Mitophagy reduces the formation of reactive oxygen species and is considered as a protective cellular process. Mitochondrial dysfunction and deficits of mitophagy have important roles in aging and especially in neurodegenerative disorders such as Alzheimer's disease (AD). Targeting mitophagy pathways has been suggested to have potential therapeutic effects against AD. In this review, we aim to briefly discuss the emerging concepts on mitophagy, molecular regulation of the mitophagy process, current mitophagy detection methods, and mitophagy dysfunction in AD. Finally, we will also briefly examine the stimulation of mitophagy as an approach for attenuating neurodegeneration in AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms. Abstract of the paper: Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged mitochondria (mitophagy) is also compromised in AD, resulting in the accumulation of dysfunctional mitochondria. Results in animal and cellular models of AD and in patients with sporadic late-onset AD suggest that impaired mitophagy contributes to synaptic dysfunction and cognitive deficits by triggering Aβ and Tau accumulation through increases in oxidative damage and cellular energy deficits; these, in turn, impair mitophagy. Interventions that bolster mitochondrial health and/or stimulate mitophagy may therefore forestall the neurodegenerative process in AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitochondria in Aging and Alzheimer's Disease: Focus on Mitophagy. Abstract of the paper: Alzheimer's disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in the brain, which leads to the loss of neurons. Under the microscope, the function of mitochondria is uniquely primed to play a pivotal role in neuronal cell survival, energy metabolism, and cell death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, and defective mitophagy in neurons are early indicators of AD. This review article summarizes the latest development of mitochondria in AD: 1) disease mechanism pathways, 2) the importance of mitochondria in neuronal functions, 3) metabolic pathways and functions, 4) the link between mitochondrial dysfunction and mitophagy mechanisms in AD, and 5) the development of potential mitochondrial-targeted therapeutics and interventions to treat patients with AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy in Alzheimer's disease: Molecular defects and therapeutic approaches. Abstract of the paper: Mitochondrial dysfunctions are central players in Alzheimer's disease (AD). In addition, impairments in mitophagy, the process of selective mitochondrial degradation by autophagy leading to a gradual accumulation of defective mitochondria, have also been reported to occur in AD. We provide an updated overview of the recent discoveries and advancements on mitophagic molecular dysfunctions in AD-derived fluids and cells as well as in AD brains. We discuss studies using AD cellular and animal models that have unraveled the contribution of relevant AD-related proteins (Tau, Aβ, APP-derived fragments and APOE) in mitophagy failure. In accordance with the important role of impaired mitophagy in AD, we report on various therapeutic strategies aiming at stimulating mitophagy in AD and we summarize the benefits of these potential therapeutic strategies in human clinical trials.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitochondrial mechanisms in Alzheimer's disease: quest for therapeutics. Abstract of the paper: Mitochondrial function is essential for maintaining neuronal integrity, because neurons have a high energy demand. Neurodegenerative diseases, such as Alzheimer's disease (AD), are exacerbated by mitochondrial dysfunction. Mitochondrial autophagy (mitophagy) attenuates neurodegenerative diseases by eradicating dysfunctional mitochondria. In neurodegenerative disorders, there is disruption of the mitophagy process. High levels of iron also interfere with the mitophagy process and the mtDNA released after mitophagy is proinflammatory and triggers the cGAS-STING pathway that aids AD pathology. In this review, we critically discuss the factors that affect mitochondrial impairment and different mitophagy processes in AD. Furthermore, we discuss the molecules used in mouse studies as well as clinical trials that could result in potential therapeutics in the future. Teaser: This review reports the novel therapeutic molecules that are underway in clinical trials for neurodegenerative diseases like Alzheimer's disease, demonstrating how mitochondria become dysfunctional and how they can be rescued.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy regulation in aging and neurodegenerative disease. Abstract of the paper: Mitochondria are the primary cellular energy generators, supplying the majority of adenosine triphosphate through oxidative phosphorylation, which is necessary for neuron function and survival. Mitophagy is the metabolic process of eliminating dysfunctional or redundant mitochondria. It is a type of autophagy and it is crucial for maintaining mitochondrial and neuronal health. Impaired mitophagy leads to an accumulation of damaged mitochondria and proteins leading to the dysregulation of mitochondrial quality control processes. Recent research shows the vital role of mitophagy in neurons and the pathogenesis of major neurodegenerative diseases. Mitophagy also plays a major role in the process of aging. This review describes the alterations that are being caused in the mitophagy process at the molecular level in aging and in neurodegenerative diseases, particularly Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis, also looks at how mitophagy can be exploited as a therapeutic target for these diseases.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy in neurodegeneration and aging. Abstract of the paper: Mitochondrial dysfunction contributes to normal aging and a wide spectrum of age-related diseases, including neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. It is important to maintain a healthy mitochondrial population which is tightly regulated by proteolysis and mitophagy. Mitophagy is a specialized form of autophagy that regulates the turnover of damaged and dysfunctional mitochondria, organelles that function in producing energy for the cell in the form of ATP and regulating energy homeostasis. Mechanistic studies on mitophagy across species highlight a sophisticated and integrated cellular network that regulates the degradation of mitochondria. Strategies directed at maintaining a healthy mitophagy level in aged individuals might have beneficial effects. In this review, we provide an updated mechanistic overview of mitophagy pathways and discuss the role of reduced mitophagy in neurodegeneration. We also highlight potential translational applications of mitophagy-inducing compounds, such as NAD+ precursors and urolithins.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy pathways and Alzheimer's disease: From pathogenesis to treatment. Abstract of the paper: Alzheimer's disease (AD) is an age-dependent, incurable mental illness that is associated with the accumulation of aggregates of amyloid-beta (Aβ) and hyperphosphorylated tau fragments (p-tau). Detailed studies on postmortem AD brains, cell lines, and mouse models of AD have shown that numerous cellular alterations, including mitochondrial deficits, synaptic disruption and glial/astrocytic activation, are involved in the disease process. Mitophagy is a cellular process by which damaged/weakened mitochondria are selectively eliminated from the cell. In AD, impairments in mitophagy trigger the gradual accumulation of defective mitochondria. This review will focus on the recent progress in understanding the molecular mechanisms and pathological role of mitophagy and its implications for AD pathogenesis. We will also discuss the novel concept of the regulation of mitophagy as a therapeutic avenue for the prevention and treatment of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Aging-Dependent Mitophagy Dysfunction in Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is the most common late-onset dementia characterized by the deposition of extracellular amyloid plaques and formation of intracellular neurofibrillary tangles, which eventually lead to neuronal loss and cognitive deficits. Multiple lines of evidence indicate that mitochondrial dysfunction is involved in the initiation and progression of AD. As essential machinery for mitochondrial quality control, mitophagy plays a housekeeping role in neuronal cells by eliminating dysfunctional or excessive mitochondria. At present, mounting evidence support that the activity of mitophagy markedly declines in human brains during aging. Impaired mitophagy and mitochondrial dysfunction were causally linked to bioenergetic deficiency, oxidative stress, microglial activation, and chronic inflammation, thereby aggravating the Aβ and tau pathologies and leading to neuron loss in AD. This review summarizes recent evidence for age-associated mitophagy decline during human aging and provides an overview of mitochondrial dysfunction involved in the process of AD. It also discusses the underlying mechanisms through which defective mitophagy leads to neuronal cell death in AD. Therapeutic interventions aiming to restore mitophagy functions can be used as a strategy for ameliorating AD pathogenesis.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Culprit or Bystander: Defective Mitophagy in Alzheimer's Disease. Abstract of the paper: Mitophagy is a selective engulfment and degradation of damaged mitochondria through the cellular autophagy machinery, a major mechanism responsible for mitochondrial quality control. Increased accumulation of damaged mitochondria in the Alzheimer's disease (AD) human brain are evident, although underlying mechanisms largely elusive. Recent studies indicate impaired mitophagy may contribute to the accumulation of damaged mitochondria in cross-species AD animal models and in AD patient iPSC-derived neurons. Studies from AD highlight feed-forward vicious cycles between defective mitophagy, and the principal AD pathological hallmarks, including amyloid-β plaques, tau tangles, and inflammation. The concomitant and intertwined connections among those hallmarks of AD and the absence of a real humanized AD rodent model present a challenge on how to determine if defective mitophagy is an early event preceding and causal of Tau/Aβ proteinopathies. Whilst further studies are required to understand these relationships, targeting defective mitophagy holds promise as a new therapeutic strategy for AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Microglial mitophagy mitigates neuroinflammation in Alzheimer's disease. Abstract of the paper: In neurons, defective mitophagy results in accumulation of damaged mitochondria, and finally leading to various neurodegenerative diseases, including Alzheimer's disease (AD). However, how mitophagy is defective in AD as well as how defective mitophagy contributes to AD is not fully understood. We give commentary on recent progress of this topic, highlighting the importance of mitophagy not only in neurons, but also in microglia, in forestalling pathology and cognitive decline in different animal models of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Alterations in Mitochondrial Quality Control in Alzheimer's Disease. Abstract of the paper: Mitochondrial dysfunction is one of the earliest and most prominent features in the brains of Alzheimer's disease (AD) patients. Recent studies suggest that mitochondrial dysfunction plays a pivotal role in the pathogenesis of AD. Neurons are metabolically active cells, causing them to be particularly dependent on mitochondrial function for survival and maintenance. As highly dynamic organelles, mitochondria are characterized by a balance of fusion and fission, transport, and mitophagy, all of which are essential for maintaining mitochondrial integrity and function. Mitochondrial dynamics and mitophagy can therefore be identified as key pathways in mitochondrial quality control. Tremendous progress has been made in studying changes in these key aspects of mitochondrial biology in the vulnerable neurons of AD brains and mouse models, and the potential underlying mechanisms of such changes. This review highlights recent findings on alterations in the mitochondrial dynamics and mitophagy in AD and discusses how these abnormalities impact mitochondrial quality control and thus contribute to mitochondrial dysfunction in AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitophagy in neurodegeneration: an opportunity for therapy? Abstract of the paper: Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are characterized by distinct clinical manifestations and neuropathological hallmarks, but they also share common features like mitochondrial dysfunction. As strategic organelles in several cellular pathways, including life/death decision, it is crucial to maintain a healthy mitochondrial pool to ensure cellular homeostasis. Macroautophagy is a pathway of lysosomal-dependent degradation of cytosolic portions, such as misfolded proteins or damaged organelles. In the last decade this process has gained new frontiers and is currently seen as a specific, rather than a random process. In this regard the term mitophagy came to describe the selective degradation of mitochondria by autophagy. This review is intended to discuss mitochondrial dysfunction in Alzheimer's and Parkinson's diseases. The recent developments on the molecular basis of mitophagy will be also argued. Finally, we will discuss mitophagy as a potential therapeutic target for neurodegenerative diseases.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mechanisms and roles of mitophagy in neurodegenerative diseases. Abstract of the paper: Mitochondria are double-membrane-encircled organelles existing in most eukaryotic cells and playing important roles in energy production, metabolism, Ca2+ buffering, and cell signaling. Mitophagy is the selective degradation of mitochondria by autophagy. Mitophagy can effectively remove damaged or stressed mitochondria, which is essential for cellular health. Thanks to the implementation of genetics, cell biology, and proteomics approaches, we are beginning to understand the mechanisms of mitophagy, including the roles of ubiquitin-dependent and receptor-dependent signals on damaged mitochondria in triggering mitophagy. Mitochondrial dysfunction and defective mitophagy have been broadly associated with neurodegenerative diseases. This review is aimed at summarizing the mechanisms of mitophagy in higher organisms and the roles of mitophagy in the pathogenesis of neurodegenerative diseases. Although many studies have been devoted to elucidating the mitophagy process, a deeper understanding of the mechanisms leading to mitophagy defects in neurodegenerative diseases is required for the development of new therapeutic interventions, taking into account the multifactorial nature of diseases and the phenotypic heterogeneity of patients.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitochondrial integrity in neurodegeneration. Abstract of the paper: The mitochondrion is a unique organelle with a diverse range of functions. Mitochondrial dysfunction is a key pathological process in several neurodegenerative diseases. Mitochondria are mostly important for energy production; however, they also have roles in Ca2+ homeostasis, ROS production, and apoptosis. There are two major systems in place, which regulate mitochondrial integrity, mitochondrial dynamics, and mitophagy. These two processes remove damaged mitochondria from cells and protect the functional mitochondrial population. These quality control systems often become dysfunctional during neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, causing mitochondrial dysfunction and severe neurological symptoms.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Defective Autophagy and Mitophagy in Aging and Alzheimer's Disease. Abstract of the paper: Aging is the time-dependent process that all living organisms go through characterized by declining physiological function due to alterations in metabolic and molecular pathways. Many decades of research have been devoted to uncovering the cellular changes and progression of aging and have revealed that not all organisms with the same chronological age exhibit the same age-related declines in physiological function. In assessing biological age, factors such as epigenetic changes, telomere length, oxidative damage, and mitochondrial dysfunction in rescue mechanisms such as autophagy all play major roles. Recent studies have focused on autophagy dysfunction in aging, particularly on mitophagy due to its major role in energy generation and reactive oxidative species generation of mitochondria. Mitophagy has been implicated in playing a role in the pathogenesis of many age-related diseases, including Alzheimer's disease (AD), Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The purpose of our article is to highlight the mechanisms of autophagy and mitophagy and how defects in these pathways contribute to the physiological markers of aging and AD. This article also discusses how mitochondrial dysfunction, abnormal mitochondrial dynamics, impaired biogenesis, and defective mitophagy are related to aging and AD progression. This article highlights recent studies of amyloid beta and phosphorylated tau in relation to autophagy and mitophagy in AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Mitochondrial Dysfunction and Oxidative Stress in Alzheimer's Disease. Abstract of the paper: Mitochondria play a pivotal role in bioenergetics and respiratory functions, which are essential for the numerous biochemical processes underpinning cell viability. Mitochondrial morphology changes rapidly in response to external insults and changes in metabolic status via fission and fusion processes (so-called mitochondrial dynamics) that maintain mitochondrial quality and homeostasis. Damaged mitochondria are removed by a process known as mitophagy, which involves their degradation by a specific autophagosomal pathway. Over the last few years, remarkable efforts have been made to investigate the impact on the pathogenesis of Alzheimer's disease (AD) of various forms of mitochondrial dysfunction, such as excessive reactive oxygen species (ROS) production, mitochondrial Ca2+ dyshomeostasis, loss of ATP, and defects in mitochondrial dynamics and transport, and mitophagy. Recent research suggests that restoration of mitochondrial function by physical exercise, an antioxidant diet, or therapeutic approaches can delay the onset and slow the progression of AD. In this review, we focus on recent progress that highlights the crucial role of alterations in mitochondrial function and oxidative stress in the pathogenesis of AD, emphasizing a framework of existing and potential therapeutic approaches.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Role of mitochondrial dysfunction in Alzheimer's disease. Abstract of the paper: Abnormalities in mitochondrial function relate to the spectrum of pathological changes seen in Alzheimer's disease. Here we review the causes and consequences of mitochondrial disturbances in Alzheimer's disease as well as how this information might impact on therapeutic approaches to this disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: mitophagy removes the defective or damaged mitochondria through several pathways 10 11 12 13 Title of the paper: Defective mitophagy in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive, mental illness without cure. Several years of intense research on postmortem AD brains, cell and mouse models of AD have revealed that multiple cellular changes are involved in the disease process, including mitochondrial abnormalities, synaptic damage, and glial/astrocytic activation, in addition to age-dependent accumulation of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). Synaptic damage and mitochondrial dysfunction are early cellular changes in the disease process. Healthy and functionally active mitochondria are essential for cellular functioning. Dysfunctional mitochondria play a central role in aging and AD. Mitophagy is a cellular process whereby damaged mitochondria are selectively removed from cell and mitochondrial quality and biogenesis. Mitophagy impairments cause the progressive accumulation of defective organelle and damaged mitochondria in cells. In AD, increased levels of Aβ and p-tau can induce reactive oxygen species (ROS) production, causing excessive fragmentation of mitochondria and promoting defective mitophagy. The current article discusses the latest developments of mitochondrial research and also highlights multiple types of mitophagy, including Aβ and p-tau-induced mitophagy, stress-induced mitophagy, receptor-mediated mitophagy, ubiquitin mediated mitophagy and basal mitophagy. This article also discusses the physiological states of mitochondria, including fission-fusion balance, Ca2+ transport, and mitochondrial transport in normal and diseased conditions. Our article summarizes current therapeutic interventions, like chemical or natural mitophagy enhancers, that influence mitophagy in AD. Our article discusses whether a partial reduction of Drp1 can be a mitophagy enhancer and a therapeutic target for mitophagy in AD and other neurological diseases.

False

CitationGPTRetr580

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Triple conjugated carbon dots as a nano-drug delivery model for glioblastoma brain tumors. Abstract of the paper: Most of the dual nano drug delivery systems fail to enter malignant brain tumors due to a lack of proper targeting systems and the size increase of the nanoparticles after drug conjugation. Therefore, a triple conjugated system was developed with carbon dots (C-dots), which have an average particle size of 1.5-1.7 nm. C-dots were conjugated with transferrin (the targeted ligand) and two anti-cancer drugs, epirubicin and temozolomide, to build the triple conjugated system in which the average particle size was increased only up to 3.5 nm. In vitro studies were performed with glioblastoma brain tumor cell lines SJGBM2, CHLA266, CHLA200 (pediatric) and U87 (adult). The efficacy of the triple conjugated system (dual drug conjugation along with transferrin) was compared to those of dual conjugated systems (single drug conjugation along with transferrin), non-transferrin C-dots-drugs, and free drug combinations. Transferrin conjugated samples displayed the lowest cell viability even at a lower concentration. Among the transferrin conjugated samples, the triple conjugated system (C-dots-trans-temo-epi (C-DT)) was more strongly cytotoxic to brain tumor cell lines than dual conjugated systems (C-dots-trans-temo (C-TT) and C-dots-trans-epi (C-ET)). C-DT increased the cytotoxicity to 86% in SJGBM2 at 0.01 μM while C-ET and C-TT reduced it only to 33 and 8%, respectively. Not only did triple conjugated C-DT increase the cytotoxicity, but also the two-drug combination in C-DT displayed a synergistic effect.

True

CitationGPTRetr581

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Enhancing Glioblastoma-Specific Penetration by Functionalization of Nanoparticles with an Iron-Mimic Peptide Targeting Transferrin/Transferrin Receptor Complex. Abstract of the paper: Treatment of glioblastoma (GBM) remains to be the most formidable challenge because of the hindrance of the blood-brain barrier (BBB) along with the poor drug penetration into the glioma parenchyma. Nanoparticulate drug delivery systems (DDS) utilizing transferrin (Tf) as the targeting ligand to target the glioma-associated transferrin receptor (TfR) had met the problem of loss of specificity in biological environment due to the high level of endogenous Tf. Here we conjugated CRT peptide, an iron-mimicry moiety targeting the whole complex of Tf/TfR, to poly(ethylene glycol)-poly(l-lactic-co-glycolic acid) nanoparticles (CRT-NP), to open a new route to overcome such obstacle. High cellular associations, advanced transport ability through the BBB model, and penetration in 3-dimensional C6 glioma spheroids in vitro had preliminarily proved the advantages of CRT-NP over Tf-nanoparticle conjugates (Tf-NP). Compared with Tf-NP, NP, and Taxol, paclitaxel-loaded CRT-NP (CRT-NP-PTX) displayed a superior antiproliferation effect on C6 glioma cells and stronger inhibitory effect on glioma spheroids. Favored pharmacokinetics behavior and enhanced accumulation in glioma foci was observed, together with a much deeper distribution pattern in glioma parenchyma compared with unmodified nanoparticles and Tf-NP. Eventually, mice treated with CRT-NP-PTX showed a remarkably prolonged median survival compared to those treated with Taxol, NP, or Tf-NP. In conclusion, the modification of CRT to nanoparticles holds great promise for enhancement of antiglioma therapy.

False

CitationGPTRetr582

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells. Abstract of the paper: Among various cancers, pediatric brain tumors represent the most common cancer type in children and the second most common cause of cancer related deaths. Anticancer drugs and therapies, such as doxorubicin (Dox), have severe side effects on patients during chemotherapy, especially for children as their bodies are still under development. These side effects are believed to be due to the lack of a delivery system with high efficacy and targeting selectivity, resulting in serious damages of normal cells. To improve the efficacy and selectivity, the transferrin (Trans) receptor mediated endocytosis can be utilized for drug delivery system design, as transferrin receptors are expressed on the blood brain barrier (BBB) and often over expressed in brain tumor cells. Carbon dots (C-Dots) have recently emerged as benign nanoparticles in biomedical applications owing to their good water solubility, tunable surface functionalities and excellent biocompatibility. The unique characteristics of C-Dots make them promising candidates for drug delivery development. In this study, carbon dots-transferrin-doxorubicin covalent conjugate (C-Dots-Trans-Dox) was synthesized, characterized by different spectroscopic techniques and investigated for the potential application as a drug delivery system for anticancer drug doxorubicin to treat pediatric brain tumors. Our in vitro results demonstrate greater uptake of the C-Dots-Trans-Dox conjugate compared to Dox alone presumably owing to the high levels of transferrin receptors on these tumor cells. Experiment showed that C-Dots-Trans-Dox at 10 nM was significantly more cytotoxic than Dox alone, reducing viability by 14-45%, across multiple pediatric brain tumor cell lines.

False

CitationGPTRetr583

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells. Abstract of the paper: In this study, a transferrin (Tf)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (Tf)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-Tf), which produced nanosized particles (~90 nm) with a low polydispersity index (~0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127&P123-Tf enhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127&P123-Tf inhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127&P123-Tf has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.

False

CitationGPTRetr584

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Abstract of the paper: The effective treatment of malignant brain glioma is hindered by the poor transport across the blood-brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). In this study, transferrin-conjugated magnetic silica PLGA nanoparticles (MNP-MSN-PLGA-Tf NPs) were formulated to overcome these barriers. These NPs were loaded with doxorubicin (DOX) and paclitaxel (PTX), and their anti-proliferative effect was evaluated in vitro and in vivo. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 cells. The delivery and the subsequent cellular uptake of drug-loaded NPs could be enhanced by the presence of magnetic field and the usage of Tf as targeting ligand, respectively. In particular, cells treated with DOX-PTX-NPs-Tf with magnetic field showed the highest cytotoxicity as compared to those treated with DOX-PTX-NPs-Tf, DOX-PTX-NPs, DOX-PTX-NPs-Tf with free Tf. The in vivo therapeutic efficacy of drug-loaded NPs was evaluated in intracranial U-87 MG-luc2 xenograft of BALB/c nude mice. In particular, the DOX-PTX-NPs-Tf treatment exhibited the strongest anti-glioma activity as compared to the PTX-NPs-Tf, DOX-NPs-Tf or DOX-PTX-NPs treatment. Mice did not show acute toxicity after administrating with blank MNP-MSN-PLGA-Tf NPs. Overall, MNP-MSN-PLGA-Tf NPs are promising carriers for the delivery of dual drugs for effective treatment of brain glioma.

False

CitationGPTRetr585

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Ferritin Nanocarrier Traverses the Blood Brain Barrier and Kills Glioma. Abstract of the paper: Over the last decades, considerable efforts have been put into developing active nanocarrier systems that cross the blood brain barrier (BBB) to treat brain-related diseases such as glioma tumors. However, to date none have been approved for clinical usage. Here, we show that a human H-ferritin (HFn) nanocarrier both successfully crosses the BBB and kills glioma tumor cells. Its principle point of entry is the HFn receptor (transferrin receptor 1), which is overexpressed in both BBB endothelial cells (ECs) and glioma cells. Importantly, we found that HFn enters and exits the BBB via the endosome compartment. In contrast, upon specifically targeting and entering glioma cells, nearly all of the HFn accumulated in the lysosomal compartment, resulting in the killing of glioma tumor cells, with no HFn accumulation in the surrounding healthy brain tissue. Thus, HFn is an ideal nanocarrier for glioma therapy and possesses the potential to serve as a therapeutic approach against a broad range of central nervous system diseases.

False

CitationGPTRetr586

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin liposomes of docetaxel for brain-targeted cancer applications: formulation and brain theranostics. Abstract of the paper: Diagnosis and therapy of brain cancer was often limited due to low permeability of delivery materials across the blood-brain barrier (BBB) and their poor penetration into the brain tissue. This study explored the possibility of utilizing theranostic d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) liposomes as nanocarriers for minimally invasive brain-targeted imaging and therapy (brain theranostics). The aim of this work was to formulate transferrin conjugated TPGS coated theranostic liposomes, which contain both docetaxel and quantum dots (QDs) for imaging and therapy of brain cancer. The theranostic liposomes with and without transferrin decoration were prepared and characterized for their particle size, polydispersity, morphology, drug encapsulation efficiency, in-vitro release study and brain theranostics. The particle sizes of the non-targeted and targeted theranostic liposomes were found below 200 nm. Nearly, 71% of drug encapsulation efficiency was achieved with liposomes. The drug release from transferrin conjugated theranostic liposomes was sustained for more than 72 h with 70% of drug release. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non-targeted preparations.

False

CitationGPTRetr587

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Development and optimization of transferrin-conjugated nanostructured lipid carriers for brain delivery of paclitaxel using Box-Behnken design. Abstract of the paper: The treatment of brain cancer remains one of the most difficult challenges in oncology. The purpose of this study was to develop transferrin-conjugated nanostructured lipid carriers (Tf-NLCs) for brain delivery of paclitaxel (PTX). PTX-loaded NLCs (PTX-NLCs) were prepared using solvent evaporation method and the impact of various formulation variables were assessed using Box-Behnken design. Optimized PTX-NLC was coupled with transferrin as targeting ligand and in vitro cytotoxicity of it was investigated against U-87 brain cancer cell line. As a result, 14.1 mg of cholesterol, 18.5 mg of triolein, and 0.5% poloxamer were used to prepare the optimal formulation. Mean particle size (PS), zeta potential (ZP), entrapment efficiency (EE), drug loading (DL), mean release time (MRT) of adopted formulation were confirmed to be 205.4 ± 11 nm, 25.7 ± 6.22 mV, 91.8 ± 0.5%, 5.38 ± 0.03% and 29.3 h, respectively. Following conjugation of optimized PTX-NLCs with transferrin, coupling efficiency was 21.3 mg transferrin per mmol of stearylamine; PS and MRT were increased while ZP, EE and DL decreased non-significantly. Tf-PTX-NLCs showed higher cytotoxic activity compared to non-targeted NLCs and free drug. These results indicated that the Tf-PTX-NLCs could potentially be exploited as a delivery system in brain cancer cells.

False

CitationGPTRetr588

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin/transferrin receptor-mediated drug delivery. Abstract of the paper: Since transferrin was discovered more than half a century ago, a considerable effort has been made towards understanding tranferrin-mediated iron uptake. However, it was not until recently with the identification and characterization of several new genes related to iron homeostasis, such as the hemochromatosis protein HFE and the iron transporter DMT1, that our knowledge has been advanced dramatically. A major pathway for cellular iron uptake is through internalization of the complex of iron-bound transferrin and the transferrin receptor, which is negatively modulated by HFE, a protein related to hereditary hemochromatosis. Iron is released from transferrin as the result of the acidic pH in endosome and then is transported to the cytosol by DMT1. The iron is then utilized as a cofactor by heme and ribonucleotide reductase or stored in ferritin. Apart from iron, many other metal ions of therapeutic and diagnostic interests can also bind to transferrin at the iron sites and their transferrin complexes can be recognized by many cells. Therefore, transferrin has been thought as a "delivery system" for many beneficial and harmful metal ions into the cells. Transferrin has also be widely applied as a targeting ligand in the active targeting of anticancer agents, proteins, and genes to primary proliferating malignant cells that overexpress transferrin receptors. This is achieved by conjugation of transferrin with drugs, proteins, hybride systems with marcomolecules and as liposomal-coated systems. Conjugates of anticancer drugs with transferrin can significantly improve the selectivity and toxicity and overcome drug resistance, thereby leading to a better treatment. The coupling of DNA to transferrin via a polycation such as polylysine or via cationic liposomes can target and transfer of the extrogenous DNA particularly into proliferating cells through receptor-mediated endocytosis. These kinds of non-viral vectors are potential alternatives to viral vectors for gene therapy, if the transfection efficiency can be improved. Moreover, transferrin receptors have shown potentials in delivery of therapeutic drugs or genes into the brain across blood-brain barrier.

False

CitationGPTRetr589

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: The enhancement of siPLK1 penetration across BBB and its anti glioblastoma activity in vivo by magnet and transferrin co-modified nanoparticle. Abstract of the paper: In order to enhance the penetration of small interference RNA against the polo-like kinase I (siPLK1) across BBB to treat glioblastoma (GBM), transferrin (Tf) modified magnetic nanoparticle (Tf-PEG-PLL/MNP@siPLK1) was prepared. The in vitro experiments indicated that Tf-PEG-PLL/MNP@siPLK1 enhanced the cellular uptake of siPLK1, which resulted in an increase of gene silencing effect and cytotoxicity of Tf-PEG-PLL/MNP@siPLK1 on U87 cells. Besides, Tf-PEG-PLL/MNP@siPLK1 significantly inhibited the growth of U87 glioblastoma spheroids and markedly increased the BBB penetration efficiency of siPLK1 with the application of external magnetic field in in-vitro BBB model. The in vivo experiments indicated that siPLK1 selectively accumulated in the brain tissue, and markedly reduced tumor volume and prolonged the survival time of GBM-bearing mice after Tf-PEG-PLL/MNP@siPLK1 was injected to GBM-bearing mice via tail vein. The above data indicated that magnet and transferrin co-modified nanoparticle enhanced siPLK1 penetration across BBB and increased its anti GBM activity in vivo.

False

CitationGPTRetr590

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin-modified nanoparticles for targeted delivery of Asiatic acid to glioblastoma cells. Abstract of the paper: AIMS Glioblastoma (GBM) is the most common and deadliest type of brain cancer, and the current therapeutic options are not curative, imposing the need for novel strategies. Asiatic acid (AA) is a natural compound and has been explored due to its anti-glioma activity and lower toxicity to healthy tissues compared with conventional chemotherapeutic agents. However, its poor water-solubility is an obstacle for clinical application. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were proposed in this work for Asiatic acid (AA) delivery. MAIN METHODS A central composite design was implemented to optimize the NPs, and their surface was further modified with transferrin (Tf), for targeted delivery to GBM cells. The anti-glioma activity of the NPs was studied in vitro using human GBM cells and immortalized human astrocytes. KEY FINDINGS The NPs exhibited a mean size smaller than 200 nm, with low polydispersity and negative zeta potential, indicating their suitability for brain tumor delivery. The NPs also exhibited high encapsulation efficiency and maintained a slow and controlled release of AA for 20 days. In vitro cell studies showed that NPs were able to maintain the anti-glioma activity of the natural compound and that the surface modification with Tf molecules was able to increase the cellular uptake in GBM cells, enhancing their selectivity and decreasing toxicity in healthy cells. SIGNIFICANCE Overall, this work provided guidance for designing brain-targeting delivery systems of natural compounds.

False

CitationGPTRetr591

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Assessing transferrin modification of liposomes by atomic force microscopy and transmission electron microscopy. Abstract of the paper: Site-specific delivery of drugs and therapeutics can significantly reduce drug toxicity and increase the therapeutic effect. Transferrin (Tf) is one suitable ligand to be conjugated to drug delivery systems to achieve site-specific targeting, due to its specific binding to transferrin receptors (TfR), expressed on several cell types of therapeutic interest. TfRs have been reported to be highly expressed on the surfaces of tumour cells and the well-characterised and efficient mechanism of internalisation of Tf has been exploited for the delivery of anticancer drugs, proteins, and therapeutic genes into primarily proliferating malignant cells. Liposomes are effective vehicles for drugs, genes and vaccines and can be easily modified with proteins, antibodies, and other appropriate ligands, resulting in attractive formulations for targeted drug delivery. In this study, we used atomic force microscopy (AFM) and transmission electron microscopy (TEM) to confirm the conjugation of Tf to liposomes by three different coupling methods. In addition, the conventional assays for quantification of protein amount (BCA) and phospholipid content (according to Steward) were performed. AFM and TEM were able to display Tf-molecules on the liposomal surfaces and can be routinely used to obtain additional visual information on the protein-drug carrier conjugation in a fast and reliable manner.

False

CitationGPTRetr592

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin functionalized chitosan-PEG nanoparticles for targeted delivery of paclitaxel to cancer cells. Abstract of the paper: The present investigation was aimed to utilize the stealth property of polyethylene glycol (PEG) modified chitosan nanoparticles (NPs) and active targeting function of transferrin (Tf) by transferrin receptor-mediated endocytosis to promote drug delivery to cancer cells. Paclitaxel (PTX) loaded nanoparticles (PTX-NP) were prepared by solvent evaporation method; PEGylation was carried out by coupling amine group present on the surface of NPs with hydroxyl group present on the PEG (NP-PEG). Tf conjugation was carried out by coupling carboxylic group present on the surface of ligand and hydroxyl group present on the PEG (NP-PEG-Tf). The uptake of NP-PEG-Tf into cancer cells was found to be higher as compared to non-targeted NPs. Compared with free PTX, PTX-NPs and PTX-NPs-PEG, the PTX-NPs-PEG-Tf demonstrated higher cytotoxicity to human Non-Small Cell Lung cancer cell lines (HOP-62), higher intracellular uptake especially in nuclei and lower hemolytic toxicity. Tf conjugated NPs showed increased retention time in the lungs as well as in blood. These findings indicate that Tf conjugated PEGylated nanoparticles are promising nanoconstructs for the delivery of anti-cancer drugs to cancer cells.

False

CitationGPTRetr593

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Induced expression of P-gp and BCRP transporters on brain endothelial cells using transferrin functionalized nanostructured lipid carriers: A first step of a potential strategy for the treatment of Alzheimer's disease. Abstract of the paper: P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are two transporters expressed in human neural stem/progenitor cells and at the Blood-Brain Barrier (BBB) level with decreased activity in the early stage of Alzheimer's disease (AD). Both proteins, have a protective role for the embryonic stem cells in the early developmental step, maintaining them in an undifferentiated state, and limit the access of exogenous and endogenous agents to the brain. Recently, MC111 selected from a P-gp/BCRP ligands library was investigated as multitarget strategy for AD treatment, considering its ability to induce the expression and activity of both proteins. However, MC111 clinical use could be limited for the ubiquitous physiological expression of efflux transporters and its moderate toxicity towards endothelial cells. Therefore, a selective MC111 delivery system based on nanostructured lipid carriers (NLC) functionalized with transferrin were developed. The results proved the formation of NLC with average size about 120 nm and high drug encapsulation efficiency (EE% greater than 50). In vitro studies on hCMEC/D3 cells revealed that the MC111 was selectively released by NLC at BBB level and then inducing the activity and expression of BCRP and P-gp, involved in the clearance of amyloid β peptide on brain endothelial cells.

False

CitationGPTRetr594

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma. Abstract of the paper: Glioblastomas (GBMs) are highly aggressive brain tumors with a very grim prognosis even after multi-modal therapeutic regimens. Conventional chemotherapeutic agents frequently lead to drug resistance and result in severe toxicities to non-cancerous tissues. Resveratrol (RES), a natural polyphenol with pleiotropic health benefits, has proven chemopreventive effects in all the stages of cancer including initiation, promotion and progression. However, the poor physico-chemical properties of RES severely limit its use as a free drug. In this study, RES was loaded into PEGylated liposomes (RES-L) to counter its drawbacks as a free drug. Since transferrin receptors (TfRs) are up-regulated in GBM, the liposome surface was modified with transferrin moieties (Tf-RES-L) to make them cancer cell-specific. The liposomal nanomedicines developed in this project were aimed at enhancing the physico-chemical properties of RES and exploiting the passive and active targeting capabilities of liposomes to effectively treat GBM. The RES-L were stable, had a good drug-loading capacity, prolonged drug-release in vitro and were easily scalable. Flow cytometry and confocal microscopy were used to study the association with, and internalization of, Tf-L into U-87 MG cells. The Tf-RES-Ls were significantly more cytotoxic and induced higher levels of apoptosis accompanied by activation of caspases 3/7 in GBM cells when compared to free RES or RES-L. The ability of RES to arrest cells in the S-phase of the cell cycle, and selectively induce production of reactive oxygen species in cancer cells were probably responsible for its cytotoxic effects. The therapeutic efficacy of RES formulations was evaluated in a subcutaneous xenograft mouse model of GBM. A tumor growth inhibition study and a modified survival study showed that Tf-RES-Ls were more effective than other treatments in their ability to inhibit tumor growth and improve survival in mice. Overall, the liposomal nanomedicines of RES developed in this project exhibited favorable in vitro and in vivo efficacies, which warrant their further investigation for the treatment of GBMs.

False

CitationGPTRetr595

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Pediatric glioblastoma target-specific efficient delivery of gemcitabine across the blood-brain barrier via carbon nitride dots. Abstract of the paper: Pediatric glioblastomas are known to be one of the most dangerous and life-threatening cancers among many others regardless of the low number of cases reported. The major obstacles in the treatment of these tumors can be identified as the lack of prognosis data and the therapeutic requirement to be able to cross the blood-brain barrier (BBB). Due to this lack of data and techniques, pediatric patients could face drastic side effects over a long-time span even after survival. Therefore, in this study, the capability of non-toxic carbon nitride dots (CNDs) to selectively target pediatric glioblastoma cells was studied in vitro. Furthermore, the nanocarrier capability and efficiency of CNDs were also investigated through conjugation of a chemotherapeutic agent and transferrin (Tf) protein. Gemcitabine (GM) was introduced into the system as a chemotherapeutic agent, which has never been successfully used for the treatment of any central nervous system (CNS) cancer. More than 95% of selective damage of SJGBM2 glioma cells was observed at 1 μM of CN-GM conjugate with almost 100% viability of non-cancerous HEK293 cells, although this ability was diminished at lower concentrations. However, further conjugation of Tf to obtain CN-GM-Tf allowed the achievement of selective targeting and prominent anti-cancer activity at a 100-fold lower concentration of 10 nM. Furthermore, both conjugates were capable of effectively damaging several other brain tumor cells, which were not well responsive towards the single treatment of GM. The capability of BBB penetration of the conjugates was observed using a zebrafish model, which confirms the CNDs' competence as an excellent nanocarrier to the CNS.

True

CitationGPTRetr596

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core. Abstract of the paper: Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

False

CitationGPTRetr597

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin coupled liposomes as drug delivery carriers for brain targeting of 5-florouracil. Abstract of the paper: Diseases and disorders of the brain are extremely difficult to treat pharmacologically because most drugs are unable to pass across the blood--brain barriers. Complex multi-strand tight junctions between adjacent cerebral endothelial cells and between choroid plexus epithelial cells form a physical barrier and prevent the passage of water soluble drugs from the blood into the brain, whereas the inward passage of lipid soluble drugs is restricted by drug efflux pumps which act as a functional barrier. In the present work, a transferrin-coupled liposomal system for brain delivery of 5-florouracil has been investigated.5-florouracil and (99m)Tc-DTPA bearing non-coupled liposomes were prepared by cast film method, which were coupled with the transferrin by incubating these liposomes with transferrin in the presence of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in saline phosphate buffer (pH 7.4). These liposomal systems were characterized for vesicle size, percent drug entrapment, and in vitro drug release. The size of the liposomes was increased on coupling with transferrin while percent drug entrapment reduced. The results of the in vitro release profile demonstrated that non-coupled liposomal formulation releases a comparatively higher percent (i.e. 74.8+/-3.21%) of drug than coupled liposomes. Results of in vivo study suggested a selective uptake of the transferrin-coupled liposomes from the brain capillary endothelial cells. In case of coupled liposomes, the level of radioactivity was 17-fold more as compared to the free radioactive agent and 13 times more with the non-coupled liposomes. Therefore, it could be concluded that using transferrin coupled liposomes the brain uptake of the drug could be enhanced.

False

CitationGPTRetr598

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: Transferrin-conjugated nanoparticles of poly(lactide)-D-alpha-tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood-brain barrier. Abstract of the paper: We developed in this research a nanoparticle system for targeted drug delivery across the blood-brain barrier (BBB), which consists of the transferrin (Tf) conjugated nanoparticles of poly(lactide)-D-alpha-Tocopheryl polyethylene glycol succinate (PLA-TPGS) diblock copolymer. The NPs were prepared by the nanoprecipitation method and characterized for their various physicochemical and pharmaceutical properties. Cellular uptake and cytotoxicity of the Tf-conjugated PLA-TPGS NPs formulation of coumarin 6 as a model imaging agent or Docetaxel as a model drug were investigated in close comparison with those for the PLGA NPs formulation, the bare PLA-TPGS NPs formulation as well as with the clinical Taxotere. The Tf-conjugated PLA-TPGS NPs formulation demonstrated great advantages over the other two NPs formulations and the original imaging/therapeutic agents. IC50 data showed that the Tf-conjugated PLA-TPGS NPs formulation of Docetaxel could be 23.4%, 16.9% and 229% more efficient than the PLGA NPs, the PLA-TPGS NPs formulations and Taxotere after 24 h treatment, respectively. Moreover, our preliminary ex vivo biodistribution investigation demonstrated that although not as satisfactory, the Tf-conjugated PLA-TPGS NPs formulation could be able to deliver imaging/therapeutic agents across the BBB.

False

CitationGPTRetr599

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: overexpression of transferrin receptor on tumor cells and endothelial cell in the bbb lead to the development of cds conjugate with transferrin and further this design was modified by hettiarachchi et al a triple conjugated cds based drug delivery system was designed with transferrin epirubicin and temozolomide with lot lower concentration that was able to reduce the cell viability of tumor cells compared to a dual conjugated system similar work with cds conjugation with gemcitabine and transferrin was able to target cns cancer cells at extremely low concentration with high potential to cross the bbb laminin411 overexpression is correlated with higher recurrence rate and short survival of gsm patients antisense oligonucleotides conjugated with polymeric nps can block the expression of laminin411 protein in glioma cells with increase in the survival time of experimental animals the presence of specific and overexpressed receptors particularly epidermal growth factor egfr on the surface of many cancer cells has made the health scientists explore factors for anticancer activity particularly in the nano formulations Title of the paper: A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy. Abstract of the paper: The treatment of a brain glioma remains one of the most difficult challenges in oncology. In the present study a delivery system was developed for targeted drug delivery across the blood-brain barrier (BBB) to the brain cancer cells. A cyclic arginine-glycine-aspartic acid (RGD) peptide and transferrin (TF) were utilized as targeting ligands. Cyclic RGD peptides are specific targeting ligands of cancer cells and TFs are ligands that specifically target the BBB and cancer cells. Liposome (LP) was used to conjugate the cyclic RGD and TFs to establish the brain glioma cascade delivery system (RGD/TF-LP). The LPs were prepared by the thin film hydration method and physicochemical characterization was conducted. In vitro cell uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could target endothelial and tumor cells, as well as penetrate the tumor cells to reach the core of the tumor spheroids. The results of the in vivo imaging further demonstrated that the RGD/TF-LP provided the highest brain distribution. As a result, the paclitaxel-loaded RGD/TF-LP presents the best antiproliferative activity against C6 cells and tumor spheroids. In conclusion, the RGD/TF-LP may precisely target brain glioma, which may be valuable for glioma imaging and therapy.

False