bluuebunny/crossref_metadata_2025 huggingface dataset:
tsRNA-00764 Regulates Estrogen and Progesterone Synthesis and Lipid Deposition by Targeting PPAR-γ in Duck Granulosa Cells
Authors: Chen Yaru , Wu Yan , Pi Jinsong , Fu Ming , Shen Jie , Zhang Hao , Du Jinping
Published: October 2024

Transfer RNA-derived small RNAs (tsRNAs) are novel regulatory small non-coding RNAs that have been found to modulate many life activities in recent years. However, the exact functions of tsRNAs in follicle development remain unclear. Follicle development is a remarkably complex process that follows a strict hierarchy and is strongly associated with reproductive performance in ducks. The process of converting small yellow follicles into hierarchal follicles is known as follicle selection, which directly determines the number of mature follicles. We performed small RNA sequencing during follicle selection in ducks and identified tsRNA-00764 as the target of interest based on tsRNA expression profiles in this study. Bioinformatics analyses and luciferase reporter assays further revealed that peroxisome proliferator-activated receptor-γ (PPAR-γ) was the target gene of tsRNA-00764. Moreover, tsRNA-00764 knockdown promoted estrogen and progesterone synthesis and lipid deposition in duck granulosa cells, while a PPAR-γ inhibitor reversed the above phenomenon. Taken together, these results demonstrate that tsRNA-00764, differentially expressed in pre-hierarchal and hierarchy follicles, modulates estrogen and progesterone synthesis and lipid deposition by targeting PPAR-γ in duck granulosa cells, serving as a potential novel mechanism of follicle selection. Overall, our findings provide a theoretical foundation for further exploration of the molecular mechanisms underlying follicle development and production performance in ducks.
Cancer Vaccines: Recent Insights and Future Directions
Authors: Malacopol Aretia-Teodora , Holst Peter Johannes
Published: October 2024

The field of cancer immunotherapy has seen incredible advancements in the past decades. mRNA-based cancer vaccines generating de novo T cell responses, particularly against tumor-specific antigens (TSAs), have demonstrated promising clinical outcomes and overcome diverse challenges. Despite the high potential of neoantigens to provide personalized immunotherapies through their tumor specificity and immunogenicity, challenges related to the scarcity of immunogenic neoepitopes have prompted continuous research towards finding new tumor-associated antigens (TAAs) and broader therapeutic frameworks, which may now learn from the genuine successes obtained with neoantigens. As an example, human endogenous retroviruses (HERVs) have emerged as potential alternatives to tumor neoantigens due to their high tumoral expression and ability to elicit both T cell reactivity and B cell responses associated with the efficacy of existing immunotherapies. This review aims to assess the status and limitations of TSA-directed mRNA cancer vaccines and the lessons that can be derived from these and checkpoint inhibitor studies to guide TAA vaccine development. We expect that shared B cell, CD4 and CD8 T cell antigen presentation will be key to stimulate continuous T cell expansion and efficacy for tumors that do not contain pre-existing tertiary lymphoid structures. When these structures are present in highly mutated tumors, the current checkpoint-based immunotherapies show efficacy even in immune privileged sites, and vaccines may hold the key to broaden efficacy to more tumor types and stages.
Cannabis-Based Phytocannabinoids: Overview, Mechanism of Action, Therapeutic Application, Production, and Affecting Environmental Factors
Authors: Jurga Marta , Jurga Anna , Jurga Kacper , Kaźmierczak Bartosz , Kuśmierczyk Katarzyna , Chabowski Mariusz
Published: October 2024

This review provides an overview of cannabis-based phytocannabinoids, focusing on their mechanisms of action, therapeutic applications, and production processes, along with the environmental factors that affect their quality and efficacy. Phytocannabinoids such as THC (∆9-tetrahydrocannabinol), CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene) exhibit significant therapeutic potential in treating various physical and mental health conditions, including chronic pain, epilepsy, neurodegenerative diseases, skin disorders, and anxiety. The cultivation of cannabis plays a crucial role in determining cannabinoid profiles, with indoor cultivation offering more control and consistency than outdoor methods. Environmental factors such as light, water, temperature, humidity, nutrient management, CO2, and the drying method used are key to optimizing cannabinoid content in inflorescences. This review outlines the need for broader data transfer between the health industry and technological production, especially in terms of what concentration and cannabinoid ratios are effective in treatment. Such data transfer would provide cultivators with information on what environmental parameters should be manipulated to obtain the required final product.
Impact of Neuron-Derived HGF on c-Met and KAI-1 in CNS Glial Cells: Implications for Multiple Sclerosis Pathology
Authors: Takano Takuma , Takano Chie , Funakoshi Hiroshi , Bando Yoshio
Published: October 2024

Demyelination and axonal degeneration are fundamental pathological characteristics of multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS). Although the molecular mechanisms driving these processes are not fully understood, hepatocyte growth factor (HGF) has emerged as a potential regulator of neuroinflammation and tissue protection in MS. Elevated HGF levels have been reported in MS patients receiving immunomodulatory therapy, indicating its relevance in disease modulation. This study investigated HGF’s neuroprotective effects using transgenic mice that overexpressed HGF. The experimental autoimmune encephalomyelitis (EAE) model, which mimics MS pathology, was employed to assess demyelination and axonal damage in the CNS. HGF transgenic mice showed delayed EAE progression, with reduced CNS inflammation, decreased demyelination, and limited axonal degeneration. Scanning electron microscopy confirmed the preservation of myelin and axonal integrity in these mice. In addition, we explored HGF’s effects using a cuprizone-induced demyelination model, which operates independently of the immune system. HGF transgenic mice exhibited significant protection against demyelination in this model as well. We also investigated the expression of key HGF receptors, particularly c-Met and KAI-1. While c-Met, which is associated with increased inflammation, was upregulated in EAE, its expression was significantly reduced in HGF transgenic mice, correlating with decreased neuroinflammation. Conversely, KAI-1, which has been linked to axonal protection and stability, showed enhanced expression in HGF transgenic mice, suggesting a protective mechanism against axonal degeneration. These findings underscore HGF’s potential in preserving CNS structure and function, suggesting it may be a promising therapeutic target for MS, offering new hope for mitigating disease progression and enhancing neuroprotection.
Toxoplasma gondii ROP5 Enhances Type I IFN Responses by Promoting Ubiquitination of STING
Authors: Jin Qi-Wang , Yu Ting , Pan Ming , Fan Yi-Min , Ge Ceng-Ceng , He Xiao-Bing , Gong Jing-Zhi , Tao Jian-Ping , Fu Bao-Quan , Jing Zhi-Zhong , Huang Si-Yang
Published: October 2024

Toxoplasma gondii is a widely spread opportunistic pathogen that can infect nearly all warm-blooded vertebrates and cause serious toxoplasmosis in immunosuppressed animals and patients. However, the relationship between the host’s innate immune system and effector proteins is poorly understood, particularly with regard to how effectors antagonize cGAS-STING signaling during T. gondii infection. In this study, the ROP5 from the PRU strain of T. gondii was found to promote cGAS-STING-mediated immune responses. Mechanistically, ROP5 interacted with STING through predicted domain 2 and modulated cGAS-STING signaling in a predicted domain 3-dependent manner. Additionally, ROP5 strengthened cGAS-STING signaling by enhancing the K63-linked ubiquitination of STING. Consistently, ROP5 deficient PRU (PRUΔROP5) induced fewer type I IFN-related immune responses and replicated faster than the parental strain in RAW264.7 cells. Taken together, this study provides new insights into the mechanism by which ROP5 regulates T. gondii infection and provides new clues for strategies to prevent and control toxoplasmosis.
Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement
Authors: Popescu Cristina , Munteanu Constantin , Anghelescu Aurelian , Ciobanu Vlad , Spînu Aura , Andone Ioana , Mandu Mihaela , Bistriceanu Roxana , Băilă Mihai , Postoiu Ruxandra-Luciana , Vlădulescu-Trandafir Andreea-Iulia , Giuvara Sebastian , Malaelea Alin-Daniel , Onose Gelu
Published: October 2024

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota–gut–brain axis, including in Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients’ gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.
AdipoRon Alleviates Liver Injury by Protecting Hepatocytes from Mitochondrial Damage Caused by Ionizing Radiation
Authors: Liu Yi , Xu Yinfen , Ji Huilin , Gao Fenfen , Ge Ruoting , Zhou Dan , Fu Hengyi , Liu Xiaodong , Ma Shumei
Published: October 2024

Radiation liver injury is a common complication of hepatocellular carcinoma radiotherapy. It is mainly caused by irreversible damage to the DNA of hepatocellular cells directly by radiation, which seriously interferes with metabolism and causes cell death. AdipoRon can maintain lipid metabolism and stabilize blood sugar by activating adiponectin receptor 1 (AdipoR1). However, the role of AdipoRon/AdipoR1 in the regulation of ionizing radiation (IR)-induced mitochondrial damage remains unclear. In this study, we aimed to elucidate the roles of AdipoRon/AdipoR1 in IR-induced mitochondrial damage in normal hepatocyte cells. We found that AdipoRon treatment rescued IR-induced liver damage in mice and mitochondrial damage in normal hepatocytes in vivo and in vitro. AdipoR1 deficiency exacerbated IR-induced oxidative stress, mitochondrial dynamics, and biogenesis disorder. Mechanistically, the absence of AdipoR1 inhibits the activity of adenosine monophosphate-activated protein kinase α (AMPKα), subsequently leading to disrupted mitochondrial dynamics by decreasing mitofusin (MFN) and increasing dynamin-related protein 1 (DRP1) protein expression. It also controls mitochondrial biogenesis by suppressing the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) and transcription factor A (TFAM) signaling pathway, ultimately resulting in impaired mitochondrial function. To sum up, AdipoRon/AdipoR1 maintain mitochondrial function by regulating mitochondrial dynamics and biogenesis through the AdipoR1-AMPKα signaling pathway. This study reveals the significant role of AdipoR1 in regulating IR-induced mitochondrial damage in hepatocytes and offers a novel approach to protecting against damage caused by IR.
Reciprocal Dynamics of Metabolism and mRNA Translation in Tumor Angiogenesis
Authors: Lidonnici Jacopo , Oberkersch Roxana E.
Published: October 2024

Angiogenesis, the process of formation of new blood vessels from pre-existing vasculature, is essential for tumor growth and metastasis. Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF) signaling is a powerful tool to combat tumor growth; however, anti-tumor angiogenesis therapy has shown limited efficacy, with survival benefits ranging from only a few weeks to months. Compensation by upregulation of complementary growth factors and switches to different modes of vascularization have made these types of therapies less effective. Recent evidence suggests that targeting specific players in endothelial metabolism is a valuable therapeutic strategy against tumor angiogenesis. Although it is clear that metabolism can modulate the translational machinery, the reciprocal relationship between metabolism and mRNA translational control during tumor angiogenesis is not fully understood. In this review, we explore emerging examples of how endothelial cell metabolism affects mRNA translation during the formation of blood vessels. A deeper comprehension of these mechanisms could lead to the development of innovative therapeutic strategies for both physiological and pathological angiogenesis.
The Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cell Secretome in Osteoarthritis: A Comprehensive Study
Authors: González-Cubero Elsa , González-Fernández Maria Luisa , Esteban-Blanco Marta , Pérez-Castrillo Saúl , Pérez-Fernández Esther , Navasa Nicolás , Aransay Ana M. , Anguita Juan , Villar-Suárez Vega
Published: October 2024

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the NF-κB pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of SOX9. These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms.
6-Gingerol Inhibits De Novo Lipogenesis by Targeting Stearoyl-CoA Desaturase to Alleviate Fructose-Induced Hepatic Steatosis
Authors: Li Pan , Wang Tingting , Qiu Hongmei , Zhang Ruoyu , Yu Chao , Wang Jianwei
Published: October 2024

Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease (NAFLD), is a worldwide liver disease without definitive or widely used therapeutic drugs in clinical practice. In this study, we confirm that 6-gingerol (6-G), an active ingredient of ginger (Zingiber officinale Roscoe) in traditional Chinese medicine (TCM), can alleviate fructose-induced hepatic steatosis. It was found that 6-G significantly decreased hyperlipidemia caused by high-fructose diets (HFD) in rats, and reversed the increase in hepatic de novo lipogenesis (DNL) and triglyceride (TG) levels induced by HFD, both in vivo and in vitro. Mechanistically, chemical proteomics and cellular thermal shift assay (CETSA)–proteomics approaches revealed that stearoyl-CoA desaturase (SCD) is a direct binding target of 6-G, which was confirmed by further CETSA assay and molecular docking. Meanwhile, it was found that 6-G could not alter SCD expression (in either mRNA or protein levels), but inhibited SCD activity (decreasing the desaturation levels of fatty acids) in HFD-fed rats. Furthermore, SCD deficiency mimicked the ability of 6-G to reduce lipid accumulation in HF-induced HepG2 cells, and impaired the improvement in hepatic steatosis brought about by 6-G treatment in HFD supplemented with oleic acid diet-induced SCD1 knockout mice. Taken together, our present study demonstrated that 6-G inhibits DNL by targeting SCD to alleviate fructose diet-induced hepatic steatosis.
Gut Microbiota and Metabolic Alterations Associated with Heart Failure and Coronary Artery Disease
Authors: Yafarova Adel A. , Dementeva Elena V. , Zlobovskaya Olga A. , Sheptulina Anna F. , Lopatukhina Elena V. , Timofeev Yuriy S. , Glazunova Evgeniya V. , Lyundup Aleksey V. , Doludin Yuriy V. , Kiselev Anton R. , Shipulin German A. , Makarov Valentin V. , Drapkina Oxana M. , Yudin Sergey M.
Published: October 2024

This study investigates the role of gut microbiota in cardiovascular diseases, with an additional focus on pro-atherogenic metabolites. We use advanced network analysis and machine learning techniques to identify key microbial features linked to coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF). This cross-sectional study included 189 participants divided into three groups: coronary artery disease (n = 93), heart failure with reduced ejection fraction (n = 43), and controls (n = 53). Assessments included physical exams, echocardiography, dietary surveys, blood analysis, and fecal analysis. Gut microbiota composition was analyzed using next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). Statistical analysis methods for testing hypotheses and correlations, alpha and beta-diversity analyses, co-occurrence networks, and machine learning were conducted using Python libraries or R packages with multiple comparisons corrected using the Benjamini–Hochberg procedure. Significant gut microbiota alterations were observed, with higher Bacillota/Bacteroidota ratios in CAD and HFrEF groups compared to controls (p < 0.001). Significant differences were observed in α-diversity indices (Pielou, Chao1, Faith) between disease groups and controls (p < 0.001). β-diversity analyses also revealed distinct microbial profiles (p = 0.0015). Interestingly, trimethylamine N-oxide (TMAO) levels were lower in CAD and HFrEF groups compared to controls (p < 0.05), while indoxyl sulfate (IS) levels were comparable between the study groups. Co-occurrence network analysis and machine learning identified key microbial features linked to these conditions, highlighting complex interactions within the gut microbiota associated with cardiovascular disease.
Comparative Analysis of Fluorescence In Situ Hybridization and Next-Generation Sequencing in Sperm Evaluation: Implications for Preimplantation Genetic Testing and Male Infertility
Authors: Moustakli Efthalia , Gkountis Antonios , Dafopoulos Stefanos , Zikopoulos Athanasios , Sotiriou Sotirios , Zachariou Athanasios , Dafopoulos Konstantinos
Published: October 2024

Pre-implantation genetic testing (PGT) is a crucial process for selecting embryos created through assisted reproductive technology (ART). Couples with chromosomal rearrangements, infertility, recurrent miscarriages, advanced maternal age, known single-gene disorders, a family history of genetic conditions, previously affected pregnancies, poor embryo quality, or congenital anomalies may be candidates for PGT. Preimplantation genetic testing for aneuploidies (PGT-A) enables the selection and transfer of euploid embryos, significantly enhancing implantation rates in assisted reproduction. Fluorescence in situ hybridization (FISH) is the preferred method for analyzing biopsied cells to identify these abnormalities. While FISH is a well-established method for identifying sperm aneuploidy, NGS offers a more comprehensive assessment of genetic material, potentially enhancing our understanding of male infertility. Chromosomal abnormalities, arising during meiosis, can lead to aneuploid sperm, which may hinder embryo implantation and increase miscarriage rates. This review provides a comparative analysis of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) in sperm evaluations, focusing on their implications for preimplantation genetic testing. This analysis explores the strengths and limitations of FISH and NGS, aiming to elucidate their roles in improving ART outcomes and reducing the risk of genetic disorders in offspring. Ultimately, the findings will inform best practices in sperm evaluations and preimplantation genetic testing strategies.
The Ways of Forming and the Erosion/Decay/Aging of Bioapatites in the Context of the Reversibility of Apatites
Authors: Lasota Agnieszka , Gorzelak Mieczysław , Turżańska Karolina , Kłapeć Wojciech , Jarzębski Maciej , Blicharski Tomasz , Pawlicz Jarosław , Wieruszewski Marek , Jabłoński Mirosław , Kuczumow Andrzej
Published: October 2024

This study primarily focused on the acid erosion of enamel and dentin. A detailed examination of the X-ray diffraction data proves that the products of the acid-caused decay of enamel belong to the family of isomorphic bioapatites, especially calcium-deficient hydroxyapatites. They are on a trajectory towards less and less crystallized substances. The increase in Bragg’s parameter d and the decrease in the energy necessary for the changes were coupled with variability in the pH. This was valid for the corrosive action of acid solutions with a pH greater than 3.5. When the processes of natural tooth aging were studied by X-ray diffraction, a clear similarity to the processes of the erosion of teeth was revealed. Scarce data on osteoporotic bones seemed to confirm the conclusions derived for teeth. The data concerning the bioapatite decays were confronted with the cycles of apatite synthesis/decay. The chemical studies, mainly concerning the Ca/P ratio in relation to the pH range of durability of popular compounds engaged in the synthesis/decay of apatites, suggested that the process of the formation of erosion under the influence of acids was much inverted in relation to the process of the formation of apatites, starting from brushite up to apatite, in an alkaline environment. Our simulations showed the shift between the family of bioapatites versus the family of apatites concerning the pH of the reaction environment. The detailed model stoichiometric equations associated with the particular stages of relevant processes were derived. The synthesis processes were alkalization reactions coupled with dehydration. The erosion processes were acid hydrolysis reactions. Formally, the alkalization of the environment during apatite synthesis is presented by introducing Ca(OH)2 to stoichiometric equations.
Essential Genes Discovery in Microorganisms by Transposon-Directed Sequencing (Tn-Seq): Experimental Approaches, Major Goals, and Future Perspectives
Authors: Fernández-García Gemma , Valdés-Chiara Paula , Villazán-Gamonal Patricia , Alonso-Fernández Sergio , Manteca Angel
Published: October 2024

Essential genes are crucial for microbial viability, playing key roles in both the primary and secondary metabolism. Since mutations in these genes can threaten organism viability, identifying them is challenging. Conditionally essential genes are required only under specific conditions and are important for functions such as virulence, immunity, stress survival, and antibiotic resistance. Transposon-directed sequencing (Tn-Seq) has emerged as a powerful method for identifying both essential and conditionally essential genes. In this review, we explored Tn-Seq workflows, focusing on eubacterial species and some yeast species. A comparison of 14 eubacteria species revealed 133 conserved essential genes, including those involved in cell division (e.g., ftsA, ftsZ), DNA replication (e.g., dnaA, dnaE), ribosomal function, cell wall synthesis (e.g., murB, murC), and amino acid synthesis (e.g., alaS, argS). Many other essential genes lack clear orthologues across different microorganisms, making them specific to each organism studied. Conditionally essential genes were identified in 18 bacterial species grown under various conditions, but their conservation was low, reflecting dependence on specific environments and microorganisms. Advances in Tn-Seq are expected to reveal more essential genes in the near future, deepening our understanding of microbial biology and enhancing our ability to manipulate microbial growth, as well as both the primary and secondary metabolism.
Glucagon-like Peptide 1 Receptor Agonists in Cardio-Oncology: Pathophysiology of Cardiometabolic Outcomes in Cancer Patients
Authors: Quagliariello Vincenzo , Canale Maria Laura , Bisceglia Irma , Iovine Martina , Giordano Vienna , Giacobbe Ilaria , Scherillo Marino , Gabrielli Domenico , Maurea Carlo , Barbato Matteo , Inno Alessandro , Berretta Massimiliano , Tedeschi Andrea , Oliva Stefano , Greco Alessandra , Maurea Nicola
Published: October 2024

Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88. In this narrative review, we highlight the biochemical properties of GLP-1 RA through a deep analysis of the clinical and preclinical evidence of the primary prevention of cardiomyopathies. The overall picture of this review encourages the study of GLP-1 RA in cancer patients with type-2 diabetes, as a potential primary prevention strategy against heart failure and atherosclerosis.
The Role of BAG3 Protein Interactions in Cardiomyopathies
Authors: Qu Hui-Qi , Wang Ju-Fang , Rosa-Campos Alexandre , Hakonarson Hakon , Feldman Arthur M.
Published: October 2024

Bcl-2-associated athanogene 3 (BAG3) plays an important function in cellular protein quality control (PQC) maintaining proteome stability. Mutations in the BAG3 gene result in cardiomyopathies. Due to its roles in cardiomyopathies and the complexity of BAG3–protein interactions, it is important to understand these protein interactions given the importance of the multifunctional cochaperone BAG3 in cardiomyocytes, using an in vitro cardiomyocyte model. The experimental assay was conducted using high pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the human AC16 cardiomyocyte cell line with BioID technology. Proteins with BAG3-interaction were identified in all the 28 hallmark gene sets enriched in idiopathic cardiomyopathies and/or ischemic disease. Among the 24 hallmark gene sets enriched in both idiopathic cardiomyopathies and ischemic disease, 15 gene sets had at least 3 proteins with BAG3-interaction. This study highlights BAG3 protein interactions, unveiling the key gene sets affected in cardiomyopathies, which help to explain the molecular mechanisms of the cardioprotective effects of BAG3. In addition, this study also highlighted the complexity of proteins with BAG3 interactions, implying unwanted effects of BAG3.
An Analysis of the Mechanism About CO2 Enrichment Promoting Carbohydrate Metabolism in Cucumber (Cucumis sativus L.) Leaves
Authors: Li Yanling , Song Hongxia , Li Xuan , Hou Leiping , Li Meilan
Published: October 2024

Elevated CO2 can affect the synthesis and distribution of photosynthetic assimilates. However, the carbohydrate metabolism molecular mechanism of cucumber leaves in response to CO2 enrichment is unclear. Therefore, it is of great significance to investigate the key functional regulatory genes in cucumber. In this study, the growth of cucumber leaves under different CO2 conditions was compared. The results showed that under CO2 enrichment, leaf area increased, the number of mesophyll cells increased, stomata enlarged, and more starch grains accumulated in the chloroplasts. Compared with the control, the starch and soluble sugar content of leaves were maximally increased by 194.1% and 55.94%, respectively; the activities of fructose-1,6-bisphosphatase (FBPase), ADPG pyrophosphorylase (AGPase), starch synthase (SSS), sucrose phosphate synthase (SPS), sucrose synthase (SS) and invertase (Inv) were maximally increased by 36.91%, 66.13%, 33.18%, 21.7%, 54.11%, and 46.01%, respectively. Through transcriptome analysis, a total of 1,582 differential expressed genes (DEGs) were identified, in which the starch and sucrose metabolism pathway was significantly enriched, and 23 genes of carbon metabolism were screened. Through metabolome analysis, a total of 22 differential accumulation metabolites (DAMs) were identified. Moreover, D-glucose and D(+)-glucose were significantly accumulated, showing upregulation 2.4-fold and 2.6-fold, respectively. Through combined analysis of transcriptome and metabolome, it was revealed that seven genes were highly related to D-glucose, and Csa6G153460 (AGPase), Csa5G612840 (β-glucosidase), and Csa4G420150 (4-α-glucanotransferase) were significantly correlated to the carbohydrate regulatory network. Furthermore, the mechanism of CO2 enrichment that promotes carbohydrate metabolism in leaves at the molecular level was revealed. This mechanism advances the development of the cell wall and leaf morphology by activating the expression of key genes and improving enzyme activity.
The Gut Microbiota Involvement in the Panorama of Muscular Dystrophy Pathogenesis
Authors: Russo Cristina , Surdo Sofia , Valle Maria Stella , Malaguarnera Lucia
Published: October 2024

Muscular dystrophies (MDs) are genetically heterogeneous diseases characterized by primary skeletal muscle atrophy. The collapse of muscle structure and irreversible degeneration of tissues promote the occurrence of comorbidities, including cardiomyopathy and respiratory failure. Mitochondrial dysfunction leads to inflammation, fibrosis, and adipogenic cellular infiltrates that exacerbate the symptomatology of MD patients. Gastrointestinal disorders and metabolic anomalies are common in MD patients and may be determined by the interaction between the intestine and its microbiota. Therefore, the gut–muscle axis is one of the actors involved in the spread of inflammatory signals to all muscles. In this review, we aim to examine in depth how intestinal dysbiosis can modulate the metabolic state, the immune response, and mitochondrial biogenesis in the course and progression of the most investigated MDs such as Duchenne Muscular Dystrophy (DMD) and Myotonic Dystrophy (MD1), to better identify gut microbiota metabolites working as therapeutic adjuvants to improve symptoms of MD.
SAT1/ALOX15 Signaling Pathway Is Involved in Ferroptosis After Skeletal Muscle Contusion
Authors: Yang Huihuang , Li Yingmin , Zhu Weihao , Feng Xiaowei , Xin Hongjian , Chen Hao , Zhang Guozhong , Zuo Min , Cong Bin , Shi Weibo
Published: October 2024

Skeletal muscle contusion (SMC) is common in daily life and clinical practice, but the molecular mechanisms underlying SMC healing are unclear. Ferroptosis, a regulated cell death type, has gained attention recently. We observed iron overload in skeletal muscle following contusion through HE and Perls staining. Abnormal iron levels are highly likely to induce ferroptosis. Therefore, we aimed to explore whether iron overload after contusion leads to ferroptosis in skeletal muscle and the underlying mechanisms, which will help us understand the effects of iron abnormalities on skeletal muscle repair. Initially, we searched SMC gene expression profiles from the GEO database and used bioinformatics analysis to reveal ferroptosis occurrence. Then, we identified the gene sat1 plays an important role in this process. We further established a rat SMC model and treated rats with ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). Our findings confirmed iron overload from SMC can lead to ferroptosis in rats. We also demonstrated that SAT1 can regulate ferroptosis by affecting ALOX15. Moreover, we constructed a ferroptosis L6 cell model and found that SAT1 knockdown significantly inhibited ALOX15 expression and reduced cellular lipid peroxidation. In conclusion, these results indicated ferroptosis can occur following SMC, and SAT1, as a key regulator, affects skeletal muscle injury healing by mediating high ALOX15 expression, which in turn regulates lipid peroxidation.
Site-Specific Integration by Circular Donor Improves CRISPR/Cas9-Mediated Homologous Recombination in Human Cell Lines
Authors: Liu Zhimei , Zhao Yue , Wu Sujun , Qi Shiyu , Qiu Yefeng , Lian Zhengxing
Published: October 2024

The technology for obtaining the high-efficiency expression of target proteins through site-specific recombination has made progress. However, using the CRISPR/Cas9 system for site-specific integration of long fragments and the expression of active proteins remains a challenge. This study optimized the linear DNA circularization system, eliminated the prokaryotic plasmid backbone on the traditional foreign gene vector, and generated a homologous arm-free circular donor template with a single guide RNA target site (sgRNA TS). This strategy significantly increased the co-transfection efficiency of the 1.6 kb template and Cas9 plasmid by 1.15-fold, and the average knock-in (KI) efficiency of the 4.7 kb long-fragment template for the two target gene sites increased by 1.3-fold. Subsequently, we used rhBCHE as a reporter gene to efficiently integrate the 5.4 kb fragment containing the gene of interest (GOI) into specific sites in the HEK293T cell line to detect the expression of the circular template at different target sites. Overall, this study further verifies that the length of the circular donor is more conducive to non-homologous integration, and more importantly, we provide a simple and optimized strategy for the construction of long-fragment site integration cell lines.
Photodynamic Therapy: Past, Current, and Future
Authors: Aebisher David , Czech Sara , Dynarowicz Klaudia , Misiołek Maciej , Komosińska-Vassev Katarzyna , Kawczyk-Krupka Aleksandra , Bartusik-Aebisher Dorota
Published: October 2024

The Greek roots of the word “photodynamic” are as follows: “phos” (φω~ς) means “light” and “dynamis” (δύναμις) means “force” or “power”. Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after the exposure to light that corresponds to an absorbance wavelength of the photosensitizer, either in the visible or near-infrared range. This process results in damage to pathological cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases associated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising results, photodynamic therapy still faces many challenges. Moreover, photodynamic therapy requires further research and improvement.
Limosilactobacillus reuteri HY7503 and Its Cellular Proteins Alleviate Endothelial Dysfunction by Increasing Nitric Oxide Production and Regulating Cell Adhesion Molecule Levels
Authors: Jeon Hyejin , Lee Daehyeop , Kim Joo-Yun , Shim Jae-Jung , Lee Jae-Hwan
Published: October 2024

Endothelial dysfunction, which is marked by a reduction in nitric oxide (NO) production or an imbalance in relaxing and contracting factor levels, exacerbates atherosclerosis by promoting the production of cell adhesion molecules and cytokines. This study aimed to investigate the effects of Limosilactobacillus reuteri HY7503, a novel probiotic isolated from raw milk, on endothelial dysfunction. Five lactic acid bacterial strains were screened for their antioxidant, anti-inflammatory, and endothelium-protective properties; L. reuteri HY7503 had the most potent effect. In a mouse model of angiotensin II-induced endothelial dysfunction, L. reuteri HY7503 reduced vascular thickening (19.78%), increased serum NO levels (226.70%), upregulated endothelial NO synthase (eNOS) expression in the aortic tissue, and decreased levels of cell adhesion molecules (intercellular adhesion molecule-1 [ICAM-1] and vascular cell adhesion molecule-1 [VCAM-1]) and serum cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]). In TNF-α-treated human umbilical vein endothelial cells (HUVECs), L. reuteri HY7503 enhanced NO production and reduced cell adhesion molecule levels. In HUVECs, surface-layer proteins (SLPs) were more effective than extracellular vesicles (exosomes) in increasing NO production and decreasing cell adhesion molecule levels. These findings suggested that L. reuteri HY7503 may serve as a functional probiotic that alleviates endothelial dysfunction.
Regenerative Inflammation: The Mechanism Explained from the Perspective of Buffy-Coat Protagonism and Macrophage Polarization
Authors: Martins Rubens Andrade , Costa Fábio Ramos , Pires Luyddy , Santos Márcia , Santos Gabriel Silva , Lana João Vitor , Costa Bruno Ramos , Santos Napoliane , de Macedo Alex Pontes , Kruel André , Lana José Fábio
Published: October 2024

The buffy-coat, a layer of leukocytes and platelets obtained from peripheral blood centrifugation, plays a crucial role in tissue regeneration and the modulation of inflammatory responses. This article explores the mechanisms of regenerative inflammation, highlighting the critical role of the buffy-coat in influencing macrophage polarization and its therapeutic potential. Macrophage polarization into M1 and M2 subtypes is pivotal in balancing inflammation and tissue repair, with M1 macrophages driving pro-inflammatory responses and M2 macrophages promoting tissue healing and regeneration. The buffy-coat’s rich composition of progenitor cells, cytokines, and growth factors—such as interleukin-10, transforming growth factor-β, and monocyte colony-stimulating factor—supports the transition from M1 to M2 macrophages, enhancing tissue repair and the resolution of inflammation. This dynamic interaction between buffy-coat components and macrophages opens new avenues for therapeutic strategies aimed at improving tissue regeneration and managing inflammatory conditions, particularly in musculoskeletal diseases such as osteoarthritis. Furthermore, the use of buffy-coat-derived therapies in conjunction with other regenerative modalities, such as platelet-rich plasma, holds promise for more effective clinical outcomes.
Towards Securing Smart Homes: A Systematic Literature Review of Malware Detection Techniques and Recommended Prevention Approach
Authors: Alshamsi Omar , Shaalan Khaled , Butt Usman
Published: October 2024

The exponential growth of the Internet of Things (IoT) sector has resulted in a surge of interconnected gadgets in smart households, thus exposing them to new cyber-attack susceptibilities. This systematic literature review investigates machine learning methodologies for detecting malware in smart homes, with a specific emphasis on identifying common threats such as denial-of-service attacks, phishing efforts, and zero-day vulnerabilities. By examining 56 publications published from 2019 to 2023, this analysis uncovers that users are the weakest link and that there is a possibility of attackers disrupting home automation systems, stealing confidential information, or causing physical harm. Machine learning approaches, namely, deep learning and ensemble approaches, are emerging as effective tools for detecting malware. In addition, this analysis highlights prevention techniques, such as early threat detection systems, intrusion detection systems, and robust authentication procedures, as crucial measures for improving smart home security. This study offers significant insights for academics and practitioners aiming to protect smart home settings from growing cybersecurity threats by summarizing the existing knowledge.
Behavioral Intentions in Metaverse Tourism: An Extended Technology Acceptance Model with Flow Theory
Authors: Wu Qi , Li Ming-Qi , Wang Jun-Hui
Published: October 2024

This study aims to develop a new theoretical framework from the perspective of the Technology Acceptance Model (TAM), incorporating flow theory, to explore the factors influencing behavioral intentions to participate in metaverse tourism. Using data from 518 respondents with metaverse experience and participation in metaverse tourism, the study employed R Studio and Structural Equation Modeling (SEM) to test the relationships between variables in the model. The results indicate that metaverse flow has a significant positive impact on users’ perceived usefulness and perceived ease of use, with flow demonstrating strong explanatory power as a precursor factor. Perceived usefulness and perceived ease of use are predictors of users’ attitudes to using metaverse technology. A positive attitude towards the metaverse can enhance users’ support for metaverse tourism and their behavioral intention to participate in it, while support also positively influences behavioral intention. Support for metaverse tourism acts as a clear mediator between attitudes and behavioral intention. The newly developed theoretical framework in this study provides a fresh perspective for metaverse tourism research and helps enrich empirical analysis in this field. By deeply analyzing tourists’ behavioral intentions, the study provides valuable insights for stakeholders to develop targeted marketing strategies and services, thus promoting the future development of metaverse tourism.
Voltage Deviation Improvement in Microgrid Operation through Demand Response Using Imperialist Competitive and Genetic Algorithms
Authors: Ghaffari Mahdi , Aly Hamed H.
Published: October 2024

In recent decades, with the expansion of distributed energy generation technologies and the increasing need for more flexibility and efficiency in energy distribution systems, microgrids have been considered a promising innovative solution for local energy supply and enhancing resilience against network fluctuations. One of the basic challenges in the operation of microgrids is the optimal management of voltage and frequency in the network, which has been the subject of extensive research in the field of microgrid operational optimization. The energy demand is considered a crucial element for energy management due to its fluctuating nature over the day. The use of demand response strategies for energy management is one of the most important factors in dealing with renewables. These strategies enable better energy management in microgrids, thereby improving system efficiency and stability. Given the complexity of optimization problems related to microgrid management, evolutionary optimization algorithms such as the Imperialist Competitive Algorithm (ICA) and Genetic Algorithm (GA) have gained great attention. These algorithms enable solving high-complexity optimization problems by considering various constraints and multiple objectives. In this paper, both ICA and GA, as well as their hybrid application, are used to significantly enhance the voltage regulation in microgrids. The integration of optimization techniques with demand response strategies improves the overall system efficiency and stability. The results proved that the hybrid method provides valuable insights for optimizing energy management systems.
A Feature-Weighted Support Vector Regression Machine Based on Hilbert–Schmidt Independence Criterion Least Absolute Shrinkage and Selection Operator
Authors: Zhang Xin , Wang Tinghua , Lai Zhiyong
Published: October 2024

Support vector regression (SVR) is a powerful kernel-based regression prediction algorithm that performs excellently in various application scenarios. However, for real-world data, the general SVR often fails to achieve good predictive performance due to its inability to assess feature contribution accurately. Feature weighting is a suitable solution to address this issue, applying correlation measurement methods to obtain reasonable weights for features based on their contributions to the output. In this paper, based on the idea of a Hilbert–Schmidt independence criterion least absolute shrinkage and selection operator (HSIC LASSO) for selecting features with minimal redundancy and maximum relevance, we propose a novel feature-weighted SVR that considers the importance of features to the output and the redundancy between features. In this approach, the HSIC is utilized to effectively measure the correlation between features as well as that between features and the output. The feature weights are obtained by solving a LASSO regression problem. Compared to other feature weighting methods, our method takes much more comprehensive consideration of weight calculation, and the obtained weighted kernel function can lead to more precise predictions for unknown data. Comprehensive experiments on real datasets from the University of California Irvine (UCI) machine learning repository demonstrate the effectiveness of the proposed method.
MRI Super-Resolution Analysis via MRISR: Deep Learning for Low-Field Imaging
Authors: Li Yunhe , Yang Mei , Bian Tao , Wu Haitao
Published: October 2024

This paper presents a novel MRI super-resolution analysis model, MRISR. Through the utilization of generative adversarial networks for the estimation of degradation kernels and the injection of noise, we have constructed a comprehensive dataset of high-quality paired high- and low-resolution MRI images. The MRISR model seamlessly integrates VMamba and Transformer technologies, demonstrating superior performance across various no-reference image quality assessment metrics compared with existing methodologies. It effectively reconstructs high-resolution MRI images while meticulously preserving intricate texture details, achieving a fourfold enhancement in resolution. This research endeavor represents a significant advancement in the field of MRI super-resolution analysis, contributing a cost-effective solution for rapid MRI technology that holds immense promise for widespread adoption in clinical diagnostic applications.