Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage. Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham (injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1 (rhwnt1), small interfering Wnt1 (siwnt1) RNA, and monoclonal antibody of Frizzled1 (anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury (within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of β-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (approval No. LLSC-20180202) in May 2017.
Multiple linear regression applied to predicting droplet size of complex perfluorocarbon nanoemulsions for biomedical applications

Abstract Multiple linear regression (MLR) modeling as a novel methodological advancement for design, development, and optimization of perfluorocarbon nanoemulsions (PFC NEs) is presented. The goal of the presented work is to develop MLR methods applicable to design, development, and optimization of PFC NEs in broad range of biomedical uses. Depending on the intended use of PFC NEs as either therapeutics or diagnostics, NE composition differs in respect to specific applications (e.g. magnetic resonance imaging, drug delivery, etc). PFC NE composition can significantly impact on PFC NE droplet size which impacts the NE performance and quality. We demonstrated earlier that microfluidization combined with sonication produces stable emulsions with high level of reproducibility. The goal of the presented work was to establish correlation between droplet size and composition in complex PFC-in-oil-in-water NEs while manufacturing process parameters are kept constant. Under these conditions, we demonstrate that MLR model can predict droplet size based on formulation variables such as amount and type of PFC oil and hydrocarbon oil. To the best of our knowledge, this is the first report where PFC NE composition was directly related to its colloidal properties and MLR used to predict colloidal properties from composition variables. Graphical Abstract
[Molecular cytogenetic characterization of five patients with myeloid leukemia and t(12;22)(p13;q12)].

OBJECTIVE To explore the clinical and laboratory characteristics of 5 patients with myeloid leukemia and t(12;22)(p13;q12). METHODS Bone marrow cells were cultured for 24 h and analyzed by standard R-banding. Rearrangement of the MN1 gene was detected by fluorescence in situ hybridization (FISH) using dual color break-apart MN1 probes. MN1-ETV6 and ETV6-MN1 fusion genes were detected by reverse transcription polymerase chain reaction (RT-PCR). And the products were subjected to direct sequencing. RESULTS Among the 5 patients, 2 had AML-M0, 2 had AML-M4, and 1 had CMM0L at the initial diagnosis. t(12;22)(p13;q12) was the primary abnormality among all patients. Rearrangements of MN1 gene were detected by FISH in all patients. MN1-ETV6 and ETV6-MN1 fusion genes were detected respectively in 4 and 3 patients. CONCLUSION t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality in myeloid leukemia, and is related to poor prognosis. allo-SCT is valuable for patients with t(12;22)(p13;q12).
Renin-angiotensin system in pre-eclampsia: everything old is new again

This review presents an update of the role of the renin-angiotensin system in normal pregnancy and pre-eclampsia. We have known for years that the circulatory renin-angiotensin system in pre-eclampsia is suppressed. We now know that the circulating renin-angiotensin system does not only have a vasoconstrictor arm, but also a vasodilator arm, which is upregulated in normal pregnancy; this balance is probably disturbed in pre-eclampsia. Recent studies show the importance of the local renin-angiotensin system in the uteroplacental unit for early placentation and regulation of placental blood flow. We discuss the possible role of autoantibodies against the AT1-receptor in pre-eclampsia and the suggestion that activation of the AT1-receptor in the placenta may lead to placental dysfunction and the clinical syndrome of pre-eclampsia.
Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview

ABSTRACT Introduction: Epigenetic mechanisms of gene regulatory control play fundamental roles in developmental morphogenesis, and, as more recently appreciated, are heavily implicated in the onset and progression of neoplastic disease, including cancer. Many epigenetic mechanisms are therapeutically targetable, providing additional incentive for understanding of their contribution to cancer and other types of neoplasia. Areas covered: The Jumonji-domain histone demethylase (JHDM) family exemplifies many of the above traits. This review summarizes the current state of knowledge of the functions and pharmacologic targeting of JHDMs in cancer and other neoplastic processes, with an emphasis on diseases affecting the pediatric population. Expert opinion: To date, the JHDM family has largely been studied in the context of normal development and adult cancers. In contrast, comparatively few studies have addressed JHDM biology in cancer and other neoplastic diseases of childhood, especially solid (non-hematopoietic) neoplasms. Encouragingly, the few available examples support important roles for JHDMs in pediatric neoplasia, as well as potential roles for JHDM pharmacologic inhibition in disease management. Further investigations of JHDMs in cancer and other types of neoplasia of childhood can be expected to both enlighten disease biology and inform new approaches to improve disease outcomes.
Arabidopsis RCD1 coordinates chloroplast and mitochondrial functions through interaction with ANAC transcription factors

Reactive oxygen species (ROS)-dependent signaling pathways from chloroplasts and mitochondria merge at the nuclear protein RADICAL-INDUCED CELL DEATH1 (RCD1). RCD1 interacts in vivo and suppresses the activity of the transcription factors ANAC013 and ANAC017, which mediate a ROS-related retrograde signal originating from mitochondrial complex III. Inactivation of RCD1 leads to increased expression of mitochondrial dysfunction stimulon (MDS) genes regulated by ANAC013 and ANAC017. Accumulating MDS gene products, including alternative oxidases (AOXs), affect redox status of the chloroplasts, leading to changes in chloroplast ROS processing and increased protection of photosynthetic apparatus. ROS alter the abundance, thiol redox state and oligomerization of the RCD1 protein in vivo, providing feedback control on its function. RCD1-dependent regulation is linked to chloroplast signaling by 3'-phosphoadenosine 5'-phosphate (PAP). Thus, RCD1 integrates organellar signaling from chloroplasts and mitochondria to establish transcriptional control over the metabolic processes in both organelles.
Integration of unaccompanied migrant youth in the United States: a call for research

ABSTRACT Between October 2013 and July 2016, over 156,000 children travelling without their guardians were apprehended at the U.S.–Mexico border and transferred to the care of the Office of Refugee Resettlement (ORR). During that same period, ORR placed over 123,000 unaccompanied migrant youth – predominantly from Central America – with a parent or other adult sponsor residing in the U.S. Following placement, local communities are tasked with integrating migrant youth, many of whom experience pre- and in-transit migration traumas, family separation, limited/interrupted schooling, and unauthorised legal status, placing them at heightened risk for psychological distress, academic disengagement, maltreatment, and human trafficking. Nonetheless, fewer than 10% of young people receive formal post-release services (PRS). This paper addresses the paucity of research on the experiences of the 90% of children and youth without access to PRS. To bridge this gap, this article: (a) describes the post-release experiences of unaccompanied youth, focusing on legal, family, health, and educational contexts; (b) identifies methodological and ethical challenges and solutions in conducting research with this population of young people and their families; and (c) proposes research to identify structural challenges to the provision of services and to inform best practices in support of unaccompanied youth. [196 words]
Conjugated Linoleic Acid Effects on Cancer, Obesity, and Atherosclerosis: A Review of Pre-Clinical and Human Trials with Current Perspectives

Obesity and its comorbidities, including type 2 diabetes and cardiovascular disease, are straining our healthcare system, necessitating the development of novel strategies for weight loss. Lifestyle modifications, such as exercise and caloric restriction, have proven effective against obesity in the short term, yet obesity persists because of the high predilection for weight regain. Therefore, alternative approaches to achieve long term sustainable weight loss are urgently needed. Conjugated linoleic acid (CLA), a fatty acid found naturally in ruminant animal food products, has been identified as a potential anti-obesogenic agent, with substantial efficacy in mice, and modest efficacy in obese human populations. Originally described as an anti-carcinogenic fatty acid, in addition to its anti-obesogenic effects, CLA has now been shown to possess anti-atherosclerotic properties. This review summarizes the pre-clinical and human studies conducted using CLA to date, which collectively suggest that CLA has efficacy against cancer, obesity, and atherosclerosis. In addition, the potential mechanisms for the many integrative physiological effects of CLA supplementation will be discussed in detail, including an introduction to the gut microbiota as a potential mediator of CLA effects on obesity and atherosclerosis.
Photobiomodulation with polychromatic light increases zone 4 survival of transverse rectus abdominis musculocutaneous flap

The aim of this study was to evaluate the effect of relatively novel approach of application of polychromatic light waves on flap survival of experimental musculocutaneous flap model and to investigate efficacy of this modality as a delay procedure to increase vascularization of zone 4 of transverse rectus abdominis musculocutaneous (TRAM) flap.
Tyrosine hydroxylase phosphorylation in vivo

Tyrosine hydroxylase (TH) is the rate‐limiting enzyme in the synthesis of the catecholamines dopamine, noradrenaline and adrenaline. One of the major mechanisms for controlling the activity of TH is protein phosphorylation. TH is phosphorylated at serine residues 8, 19, 31 and 40. There have been a number of previous reviews focused on TH phosphorylation in vitro and in situ. This review on TH phosphorylation in vivo has three main sections focusing on: (1) the methods used to investigate TH phosphorylation in vivo, including the animals used, the sacrifice procedures, the tissue preparation, the measurement of TH protein levels and TH phosphorylation and the measurement of TH activation. (2) The regulation of TH phosphorylation and its consequences in vivo, including the kinases and phosphatases acting on TH, the stoichiometry of TH phosphorylation, the proteins that bind TH and TH subcellular location. (3) The acute and prolonged TH phosphorylation changes in specific catecholaminergic tissues, including the adrenal medulla, the nigrostriatal pathway and the mesolimbic pathway.
A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations

Human adenovirus type 4 (HAdV-E4), which is intriguingly limited to military populations, causes acute respiratory disease with demonstrated morbidity and mortality implications. This respiratory pathogen contains genome identity with chimpanzee adenoviruses, indicating zoonotic origins. A signature of these “old” HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the “new” HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Special attention should be paid by clinicians to this emergent and recombinant HAdV-E4 circulating in civilian populations.
Long non-coding RNA WT1-AS inhibits cell aggressiveness via miR-203a-5p/FOXN2 axis and is associated with prognosis in cervical cancer.

OBJECTIVE Substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis and tumor progression. The lncRNA Wilms tumor 1 Antisense RNA (WT1-AS) is a potential tumor suppressor in some types of cancers. The objective of this study was to evaluate the biological roles of WT1-AS in cervical cancer. PATIENTS AND METHODS The Cancer Genome Atlas (TCGA) was used to identify differentially expressed lncRNAs in cervical carcinoma. The level of lncRNA WT1-AS in cervical carcinoma tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The lentiviral vector encoding WT1-AS (LV-WT1-AS) or miR-203a-5p mimic was transfected into cervical carcinoma cells. Cell Counting Kit-8 (CCK-8), wound healing and transwell invasion assays were applied to assess the role of WT1-AS in cervical cancer cell growth and migration. WT1-AS directly bound to miR-203a-5p was confirmed using Luciferase reporter assay. The level of forkhead box N2 (FOXN2) was assessed by quantitative Real Time-Polymerase Chain Reaction analysis. A xenograft model was constructed to explore the role of WT1-AS in cervical cancer cell growth in vivo. RESULTS WT1-AS was down-regulated in both cervical cancer tissues and cell lines. Functional analyses indicated that the over-expression of WT1-AS remarkably inhibited cervical carcinoma cell growth, migration and invasion. The results of the Luciferase reporter assays verified that miR-203a-5p is a direct target of WT1-AS. Moreover, FOXN2 was identified as a direct target gene of miR-203a-5p, and the up-regulation of miR-203a-5p reversed the inhibitory effects of WT1-AS in cervical cancer cells. CONCLUSIONS Our results demonstrated that WT1-AS was under-expressed in cervical carcinoma and suppresses cervical cancer cell growth and aggressiveness via a miR-203a-5p/FOXN2 axis.
Vaccination Guidelines for Patients with Immune-mediated Disorders Taking Immunosuppressive Therapies: Executive Summary

The use of immunosuppressive therapies for immune-mediated disease is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases, and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive and immunomodulatory agents.
Molecular Understanding of the Cardiomodulation in Myocardial Infarction and the Mechanism of Vitamin E Protection.

Myocardial infarction is a major cause of deaths globally. Modulation of several molecular mechanisms occur during the initial stages of myocardial ischemia prior to permanent cardiac tissue damage, which involve both pathogenic as well as survival pathways in the cardiomyocyte. Currently, there are increasing evidence regarding the cardioprotective role of vitamin E in alleviating the disease. This fat-soluble vitamin does not only act as a powerful antioxidant; it also has the ability to regulate several intracellular signalling pathways including HIF-1, PPAR-γ, Nrf-2, and NF-κB that influence the expression of a number of genes and their protein products. Essentially, it inhibits the molecular progression of tissue damage and preserves myocardial tissue viability. This review aims to summarize the molecular understanding of the cardiomodulation in myocardial infarction as well as the mechanism of vitamin E protection.
Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis

The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), an accepted MS model. Due to the recently described critical role of platelets in inflammation and autoimmune disease, we examined the relationship between platelets, inflammation, and anxiety-like behavior in EAE. In the elevated plus maze, EAE-induced C57BL/6J mice showed decreased time spent in the open arms relative to vehicle-only controls, demonstrating an increase in anxiety-like behavior. This effect occurred in the presence of platelet–neuron association, but absence of lymphocytic infiltration, in the hippocampal parenchyma. Platelet depletion at the pre-clinical disease stage, using antibody-mediated lysis prevented the EAE-induced increase in anxiety-like behavior, while no significant difference in distance moved was recorded. Furthermore, platelet depletion was also associated with reduction of the pro-inflammatory environment to control levels in the hippocampus and prevention of EAE disease symptomology. These studies demonstrate the high efficacy of a platelet-targeting approach in preventing anxiety-like symptoms and clinical manifestations of EAE and have implications for the treatment of neuropsychiatric symptoms in MS.
Visual Integration: A dynamic approach to the interactive combination of disparate data

This paper explores the practicality and promise of combining the 3D visual output of multiple applications as an alternative to the growing challenges of accessing, merging, and rendering data from different sources. The need for integrating data from multiple sources for the purpose of collaborative visualization has increased in recent years. However, traditional approaches are proving inadequate for several reasons: data size, incompatibility across proprietary file formats, limitations owing to data intellectual property rights, data security, and incompatibility across computing platforms. To address these challenges, this paper explores a simple approach, called Visual Integration (VI), which purposefully limits the exchange of information to only visual artifacts for generating interactive views. VI integrates 3D images from disparate sources in real-time, by comparing the depth information at every combined pixel. VI also preserves independent interactive views of the integrated data for all parties. We report on the design and implementation of a simple prototype created in OpenGL, discuss necessary improvements to create a practical solution, and explore various business scenarios that can benefit from using VI.
The Role of Matrix Protein 2 Ectodomain in the Development of Universal Influenza Vaccines

Abstract The influenza A virus matrix protein 2 ectodomain (M2e) is a universal influenza A vaccine candidate. Numerous studies in laboratory mice, but very few in natural influenza A virus hosts, have demonstrated that M2e-based vaccines can provide protection against any influenza A virus challenge. M2e-based immunity is largely accomplished by IgG and early stage clinical studies have demonstrated that the vaccine is safe. Yet M2e is considered a difficult target to develop as a vaccine: it does not offer sterilizing immunity and its mode of action relies on Fcγ receptor-mediated effector mechanisms, most likely in concert with alveolar macrophages. In a human challenge study with an H3N2 virus, treatment with a monoclonal M2e-specific human IgG was associated with a faster recovery compared to placebo treatment. If the universal influenza vaccine field incorporates this antigen into next generation vaccines, M2e could prove its merit when the next influenza pandemic strikes.
β‐adrenergic‐mediated dynamic augmentation of sarcolemmal CaV1.2 clustering and co‐operativity in ventricular myocytes

Prevailing dogma holds that activation of the β‐adrenergic receptor/cAMP/protein kinase A signalling pathway leads to enhanced L‐type CaV1.2 channel activity, resulting in increased Ca2+ influx into ventricular myocytes and a positive inotropic response. However, the full mechanistic and molecular details underlying this phenomenon are incompletely understood. CaV1.2 channel clusters decorate T‐tubule sarcolemmas of ventricular myocytes. Within clusters, nanometer proximity between channels permits Ca2+‐dependent co‐operative gating behaviour mediated by physical interactions between adjacent channel C‐terminal tails. We report that stimulation of cardiomyocytes with isoproterenol, evokes dynamic, protein kinase A‐dependent augmentation of CaV1.2 channel abundance along cardiomyocyte T‐tubules, resulting in the appearance of channel ‘super‐clusters’, and enhanced channel co‐operativity that amplifies Ca2+ influx. On the basis of these data, we suggest a new model in which a sub‐sarcolemmal pool of pre‐synthesized CaV1.2 channels resides in cardiomyocytes and can be mobilized to the membrane in times of high haemodynamic or metabolic demand, to tune excitation–contraction coupling.