A universal gene expression signature-based strategy for the high-throughput discovery of anti-inflammatory drugs.

Background: Traditional Chinese medicine (TCM) is a valuable resource for drug discovery and has demonstrated excellent efficacy in treating inflammatory diseases. This study aimed to develop a universal gene signature-based strategy for high-throughput discovery of anti-inflammatory drugs, especially Traditional Chinese medicine (TCM).

Methods: The disease gene signature of liposaccharide-stimulated THP-1 cells and drug gene signatures of 655 drug candidates were established via sequencing.

Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell.

Background: Diabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues.

Methods: Single-cell RNA sequencing data were used to create a detailed single-cell ecological landscape of DM and DFU.

Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner.

Background: Pulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.

Latent space arithmetic on data embeddings from healthy multi-tissue human RNA-seq decodes disease modules.

Computational analyses of transcriptomic data have dramatically improved our understanding of complex diseases. However, such approaches are limited by small sample sets of disease-affected material. We asked if a variational autoencoder trained on large groups of healthy human RNA sequencing (RNA-seq) data can capture the fundamental gene regulation system and generalize to unseen disease changes.

A new clinical prognosis model for breast cancer with ADSS as the hub gene.

Breast cancer (BRCA) is the most common malignant tumor and the leading cause of cancer death worldwide. Adenylosuccinate synthetase (ADSS) is highly expressed in BRCA and its subtypes malignant tumors and is associated with poor prognosis. By applying ROC curve, survival analysis, WGCNA, enrichment analysis, Cox regression model and other methods, this study explores the role of ADSS in BRCA and constructs a scoring model.

The impact of psychological stress on physiological indicators in healthcare workers: a cross-sectional study.

Background: Medical health workers play an essential role in the healthcare system and face unique workplace stressors. However, the impact of psychological stress on their physical health has received less attention compared to the general population.

Methods: We retrospectively analyzed the Self-rating Depression Scale (SDS) questionnaires and blood testing results from 1963 medical health workers.

Mechanism Study of Xiaoyao San against Nonalcoholic Steatohepatitis-Related Liver Fibrosis Based on a Combined Strategy of Transcriptome Analysis and Network Pharmacology.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD. The livers of patients with NASH are more likely to develop fibrosis.

TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma.

Background: Most head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at an advanced local stage. While immunotherapy has improved survival rates, only a minority of patients respond durably to targeted immunotherapies, posing substantial clinical challenges. We investigated the heterogeneity of the tumor microenvironment in HNSCC cohorts before and after immunotherapy by analyzing single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing datasets retrieved from public databases.

Enhancing Maturation and Translatability of Human Pluripotent Stem Cell-Derived Cardiomyocytes through a Novel Medium Containing Acetyl-CoA Carboxylase 2 Inhibitor.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) constitute an appealing tool for drug discovery, disease modeling, and cardiotoxicity screening. However, their physiological immaturity, resembling CMs in the late fetal stage, limits their utility. Herein, we have developed a novel, scalable cell culture medium designed to enhance the maturation of hPSC-CMs.

Extracellular vesicles transport RNA between cells: Unraveling their dual role in diagnostics and therapeutics.

Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far.

A pumpless liver-on-a-chip for drug hepatotoxicity analysis.

This study presents the development and validation of an innovative microfluidic liver-on-a-chip device utilizing gravity-driven perfusion for the evaluation of drug hepatotoxicity. This research involved the construction of a hydrogel-based coculture chip that integrates liver parenchymal and stellate cells within a tri-channel configuration. The assembly and operation of the liver-on-a-chip and its accompanying custom rocker were straightforward.

The complex association between the immune system and the skeletal system in osteoporosis: A study of single-cell RNA sequencing.

Objective: Osteoporosis (OP) is a disease characterized by decreased bone mass, deteriorated microstructure, and increased fragility and fracture risk. The diagnosis and prevention of OP and its complications have become major public health challenges. Therefore, exploring the complex ecological connections between the immune and skeletal systems may provide new insights for clinical prevention and treatment strategies.

Modulating the Gut Microbiota and Metabolites with Traditional Chinese Medicines: An Emerging Therapy for Type 2 Diabetes Mellitus and Its Complications.

Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications. Glucose-lowering therapy remains the main treatment for alleviating T2DM. However, conventional antidiabetic agents are fraught with numerous adverse effects, notably elevations in blood pressure and lipid levels.

Head-to-head comparison of relevant cell sources of small extracellular vesicles for cardiac repair: Superiority of embryonic stem cells.

Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair.

Proteome of Personalized Tissue-Engineered Veins.

Vascular diseases are the largest cause of death globally and impose a major global burden on healthcare. The gold standard for treating vascular diseases is the transplantation of autologous veins, if applicable. Alternative treatments still suffer from shortcomings, including low patency, lack of growth potential, the need for repeated intervention, and a substantial risk of developing infections.

The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation.

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1).

Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination.

Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma.

Study Question: Can the alleged association between ovarian endometriosis and ovarian carcinoma be substantiated by genetic analysis of endometriosis diagnosed prior to the onset of the carcinoma?

Summary Answer: The data suggest that ovarian carcinoma does not originate from ovarian endometriosis with a cancer-like genetic profile; however, a common precursor is probable.

What Is Known Already: Endometriosis has been implicated as a precursor of ovarian carcinoma based on epidemiologic studies and the discovery of common driver mutations in synchronous disease at the time of surgery. Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are the most common endometriosis-associated ovarian carcinomas (EAOCs).

A comprehensive mechanistic model of adipocyte signaling with layers of confidence.

Adipocyte signaling, normally and in type 2 diabetes, is far from fully understood. We have earlier developed detailed dynamic mathematical models for several well-studied, partially overlapping, signaling pathways in adipocytes. Still, these models only cover a fraction of the total cellular response.

Personalized tissue-engineered veins - long term safety, functionality and cellular transcriptome analysis in large animals.

Tissue engineering is a promising methodology to produce advanced therapy medicinal products (ATMPs). We have developed personalized tissue engineered veins (P-TEV) as an alternative to autologous or synthetic vascular grafts utilized in reconstructive vein surgery. Our hypothesis is that individualization through reconditioning of a decellularized allogenic graft with autologous blood will prime the tissue for efficient recellularization, protect the graft from thrombosis, and decrease the risk of rejection.

Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions.

Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells' own vehicles called extracellular vesicles (EVs).