Novel applications of metformin in the treatment of septic myocardial injury based on metabolomics and network pharmacology.

Background: While metformin has shown promise in treating septic myocardial injury (SMI), its underlying mechanisms and impact on metabolic disturbances remain poorly understood.

Methods: This study employed an integrated approach of metabolomics and network pharmacology to identify key targets and pathways through which metformin may act against SMI. Findings were validated using a lipopolysaccharide (LPS)-induced mouse model.

Androgen receptor inhibitors in treating prostate cancer.

Androgens play an important role in prostate cancer development and progression. Androgen action is mediated through the androgen receptor (AR), a ligand-dependent DNA-binding transcription factor. AR is arguably the most important target for prostate cancer treatment.

Relationship between cathepsins and cardiovascular diseases: a Mendelian randomized study.

Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated.

Single-cell RNA sequencing reveals the transcriptional heterogeneity of Tbx18-positive cardiac cells during heart development.

The T-box family transcription factor 18 (Tbx18) has been found to play a critical role in regulating the development of the mammalian heart during the primary stages of embryonic development while the cellular heterogeneity and landscape of Tbx18-positive (Tbx18+) cardiac cells remain incompletely characterized. Here, we analyzed prior published single-cell RNA sequencing (scRNA-seq) mouse heart data to explore the heterogeneity of Tbx18+ cardiac cell subpopulations and provide a comprehensive transcriptional landscape of Tbx18+ cardiac cells during their development. Bioinformatic analysis methods were utilized to identify the heterogeneity between cell groups.

All SNAP25 molecules in the vesicle-plasma membrane contact zone change conformation during vesicle priming.

In neuronal cell types, vesicular exocytosis is governed by the SNARE (soluble NSF attachment receptor) complex consisting of synaptobrevin2, SNAP25, and syntaxin1. These proteins are required for vesicle priming and fusion. We generated an improved SNAP25-based SNARE COmplex Reporter (SCORE2) incorporating mCeruelan3 and Venus and overexpressed it in SNAP25 knockout embryonic mouse chromaffin cells.

Relationship between Parkinson's disease and cardio-cerebrovascular diseases: a Mendelian randomized study.

Parkinson's disease (PD) and cardio-cerebrovascular diseases are related, according to earlier studies, but these studies have some controversy. Our aim was to assess the impact of PD on cardiocerebrovascular diseases using a Mendelian randomization (MR) method. The data for PD were single nucleotide polymorphisms (SNPs) from a publicly available genome-wide association study (GWAS) dataset containing data on 482,730 individuals.

Aberrant Activation of Immune and Non-Immune Cells Contributes to Joint Inflammation and Bone Degradation in Rheumatoid Arthritis.

Abnormal activation of multiple immune and non-immune cells and proinflammatory factors mediate the development of joint inflammation in genetically susceptible individuals. Although specific environmental factors like smoking and infections are associated with disease pathogenesis, until now, we did not know the autoantigens and arthritogenic factors that trigger the initiation of the clinical disease. Autoantibodies recognizing specific post-translationally modified and unmodified antigens are generated and in circulation before the onset of the joint disease, and could serve as diagnostic and prognostic markers.

Androgen receptor nucleocytoplasmic trafficking - A one-way journey.

The androgen receptor (AR) is a key regulator of the growth and proliferation of prostate cancer. The majority of lethal castration-resistant prostate cancer (CRPC) growth is still dependent on AR activity. The AR need to be in the nucleus to exert its biological action as a transcription factor.

The Impact of Bariatric Surgery on Pancreatic Cancer Risk: a Systematic Review and Meta-Analysis.

A growing body of evidence suggests that bariatric surgery is associated with a reduced risk of some cancers. This meta-analysis aims to determine whether bariatric surgery affects pancreatic cancer risk. We conducted a comprehensive literature search of PubMed, Embase, and Web of Science databases.

Mechanisms and targeting of proteosome-dependent androgen receptor degradation in prostate cancer.

The androgen receptor (AR) remains to be a key target for the treatment of prostate cancer, including the majority of castration-resistant prostate cancer (CRPC). AR is stabilized in CRPC and the ubiquitin-proteasome system (UPS) plays a major role in AR degradation. Targeting AR for degradation provides a potential approach to overcome the resistance of CRPC to current AR antagonists, including the next generation AR signaling inhibitors.

Transcriptomic profile analysis of the left atrium in spontaneously hypertensive rats in the early stage.

Left atrial remodeling, characterized by enlargement and hypertrophy of the left atrium and increased fibrosis, was accompanied by an increased incidence of atrial fibrillation. While before morphological changes at the early stage of hypertension, how overloaded hypertension influences the transcriptomic profile of the left atrium remains unclear. Therefore, RNA-sequencing was performed to define the RNA expressing profiles of left atrium in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats as a control group.

Vesicles Induce Mitochondrial Apoptosis by Regulating miR96-5p/Abca1 to Inhibit Osteoclastogenesis and Bone Loss.

Bone loss due to an increased osteoclast activity is common in osteoporosis and rheumatoid arthritis. For the first time, we observed an inhibition of osteoclast formation and bone resorption by outer-membrane vesicles (OMVs) from a Gram-negative, pathogenic bacterium, (P.M).

[Analyzing the clinical phenotype of heart disease caused by the double mutation of p.Gly743Arg and p.Glu1389Lys carrying the myosin heavy chain gene].

Objective: To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.

Comparative Analysis on Abnormal Methylome of Differentially Expressed Genes and Disease Pathways in the Immune Cells of RA and SLE.

We identified abnormally methylated, differentially expressed genes (DEGs) and pathogenic mechanisms in different immune cells of RA and SLE by comprehensive bioinformatics analysis. Six microarray data sets of each immune cell (CD19 B cells, CD4 T cells and CD14 monocytes) were integrated to screen DEGs and differentially methylated genes by using R package "limma." Gene ontology annotations and KEGG analysis of aberrant methylome of DEGs were done using DAVID online database.

Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis.

Rheumatoid arthritis is a chronic autoimmune syndrome associated with several genetic, epigenetic, and environmental factors affecting the articular joints contributing to cartilage and bone damage. Although etiology of this disease is not clear, several immune pathways, involving immune (T cells, B cells, dendritic cells, macrophages, and neutrophils) and nonimmune (fibroblasts and chondrocytes) cells, participate in the secretion of many proinflammatory cytokines, chemokines, proteases (MMPs, ADAMTS), and other matrix lysing enzymes that could disturb the immune balance leading to cartilage and bone damage. The presence of autoantibodies preceding the clinical onset of arthritis and the induction of bone erosion early in the disease course clearly suggest that initiation events damaging the cartilage and bone start very early during the autoimmune phase of the arthritis development.

Phytoestrogens protect joints in collagen induced arthritis by increasing IgG glycosylation and reducing osteoclast activation.

Based on previous studies, we know that estrogen can protect the joints from arthritis development by increasing IgG glycosylation and inhibiting osteoclast activation. Phytoestrogens, especially genistein and daidzein, are structurally similar to estradiol that can bind to estrogen receptors (ERs). However, how phytoestrogens affect IgG glycosylation and osteoclast activation in vivo are not investigated so far.

Autoantibodies as Diagnostic Markers and Mediator of Joint Inflammation in Arthritis.

Rheumatoid arthritis is a systemic, polygenic, and multifactorial syndrome characterized by erosive polyarthritis, damage to joint architecture, and presence of autoantibodies against several self-structures in the serum and synovial fluid. These autoantibodies (anticitrullinated protein/peptide antibodies (ACPAs), rheumatoid factors (RF), anticollagen type II antibodies, antiglucose-6 phosphate isomerase antibodies, anticarbamylated protein antibodies, and antiacetylated protein antibodies) have different characteristics, diagnostic/prognostic value, and pathological significance in RA patients. Some of these antibodies are present in the patients' serum several years before the onset of clinical disease.

Analysis of Data From Breast Diseases Treated With 5-Alpha Reductase Inhibitors for Benign Prostatic Hyperplasia.

Objective: 5-alpha reductase inhibitors (5ARIs) decrease the androgen levels in vivo and are currently used for the treatment of benign prostatic hyperplasia (BPH) in men. However, these inhibitors can also increase the risk of gynecomastia, breast tenderness, and breast cancer. Hence, we did a systematic review and meta-analysis to evaluate the rate of breast-related diseases in men treated with 5ARIs.

Precise Time Superresolution by Event Correlation Microscopy.

Fluorescence imaging is often used to monitor dynamic cellular functions under conditions of very low light intensities to avoid photodamage to the cell and rapid photobleaching. Determination of the time of a fluorescence change relative to a rapid high time-resolution event, such as an action potential or pulse stimulation, is challenged by the low photon rate and the need to use imaging frame durations that limit the time resolution. To overcome these limitations, we developed a time superresolution method named event correlation microscopy that aligns repetitive events with respect to the high time-resolution events.

Hierarchical Morphology of Polymer Blend Films Induced by Convection-Driven Solvent Evaporation.

Homogeneous thin films of polymer blends with a desired morphology are necessary because of their applications in the fields such as optoelectronics, sensors, biomedicine, and so on. The frequently employed approach for the thin film preparation, spin coating is only able to achieve a homogeneous film for a small area because of the overwhelming spin-driven solvent evaporation with increased size. Here, a convection-guided morphology formation for polystyrene:poly(methyl methacrylate) blend films is reported.

Prostaglandin E1 inhibits endocytosis in the β-cell endocytosis.

Prostaglandins inhibit insulin secretion in a manner similar to that of norepinephrine (NE) and somatostatin. As NE inhibits endocytosis as well as exocytosis, we have now examined the modulation of endocytosis by prostaglandin E1 (PGE1). Endocytosis following exocytosis was recorded by whole-cell patch clamp capacitance measurements in INS-832/13 cells.

Positively charged amino acids at the SNAP-25 C terminus determine fusion rates, fusion pore properties, and energetics of tight SNARE complex zippering.

SNAP-25 is a Q-SNARE protein mediating exocytosis of neurosecretory vesicles including chromaffin granules. Previous results with a SNAP-25 construct lacking the nine C terminal residues (SNAP-25Δ9) showed changed fusion pore properties (Fang et al., 2008), suggesting a model for fusion pore mechanics that couple C terminal zipping of the SNARE complex to the opening of the fusion pore.