Deciphering the secrets of tumor-initiating cells in pancreatic ductal adenocarcinoma microenvironment: mechanisms and therapeutic opportunities.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by poor prognosis, strong resistance to therapy, and a dense immunosuppressive tumor microenvironment (TME). A small subset of cells known as cancer stem cells (CSCs), or tumor-initiating cells (TICs), are increasingly recognized as key contributors to tumor initiation, metastasis, immune evasion, and treatment failure. These cells are defined by their self-renewal capacity, plasticity, and resistance to chemotherapeutic and targeted therapies.

Association between epigenetic age acceleration and psychiatric disorders: a bidirectional Mendelian randomization study.

Aging is a complex process influenced by genetic, environmental, and psychiatric factors. Recent evidence suggests that epigenetic age acceleration (EAA), a biomarker of biological aging, may be linked to psychiatric disorders, yet the causal direction remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationships between EAA (IEAA, HannumAA, GrimAA, PhenoAA) and ten psychiatric disorders.

Integrative causal and single-cell analyses reveal genes responsive to endocrine disruptors driving human male infertility.

Male infertility is a growing global health concern increasingly linked to environmental exposure to endocrine-disrupting chemicals (EDCs). However, the specific molecular mechanisms by which EDCs contribute to impaired reproductive function remain unclear. In this study, we systematically identified EDC-related genes using curated chemical-gene interaction databases and assessed their causal roles in male infertility through Mendelian randomization (MR) and colocalization analyses, utilizing large-scale cis-eQTL and GWAS datasets.

Integrative causal inference illuminates gene-environment interactions linking endocrine disruptors to female infertility.

Female infertility, a global health concern affecting up to 12 % of women, is influenced by genetic, hormonal, and environmental factors. Among environmental contributors, endocrine-disrupting chemicals (EDCs), which interfere with hormonal systems, have gained attention for their potential impact on reproductive health. This study used Mendelian randomization (MR) and colocalization analyses to explore the causal relationships between gene expression influenced by EDCs and female infertility.

Mapping the immune-genetic architecture of aging: A single-cell causal framework for biomarker discovery and therapeutic targeting.

Aging is a complex biological process driven by genetic and immune-mediated mechanisms, yet the causal roles of immune-cell-specific gene regulation remain unclear. In this study, we integrate single-cell expression quantitative trait loci (sc-eQTL) data with Mendelian randomization (MR) and colocalization analyses to identify immune-mediated regulatory mechanisms and therapeutic targets for aging. Using data from 14 immune cell types, we systematically evaluated 8733 eGenes for causal effects on telomere length (TL), facial aging (FA), and frailty index (FI).

The role of mitochondria-related proteins in inflammation and autoimmune diseases: a causal analysis using Mendelian randomization and colocalization.

Background: Mitochondria are central to immune regulation, inflammation, and cellular metabolism. Growing evidence suggests that mitochondrial dysfunction contributes to autoimmune disease (AD) pathogenesis by modulating inflammatory pathways and immune cell function. However, the causal relationships between mitochondria-related proteins and ADs remain unclear.

Palmitoylation Dynamics in Systemic Lupus Erythematosus: Multi-Omics Insights and Potential Therapeutic Implications.

Objective: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by immune dysregulation. The role of palmitoylation in regulating immune responses and its contribution to SLE pathogenesis remains insufficiently understood.

Methods: We conducted a multi-omics analysis using the GSE61635 dataset to identify differentially expressed genes (DEGs) in SLE.

Genomic evidence based on eQTL data implicates endocrine disruptors as environmental risk factors for estrogen receptor-positive breast cancer.

Background: Estrogen receptor-positive (ER+) breast cancer is the most common molecular subtype of breast cancer and is strongly influenced by hormonal and environmental factors. Endocrine-disrupting chemicals (EDCs), which interfere with hormone signaling, have been suggested to contribute to ER+ breast cancer risk, but causal mechanisms remain unclear.

Methods: We integrated chemical-gene interaction data from the TEDX and CTD databases with large-scale genomic datasets to investigate the relationship between EDC-regulated gene expression and ER+ breast cancer.

Exosomes as immunomodulators in autoimmune inflammation: implications for primary Sjögren's disease.

Primary Sjögren's disease (pSD) is a systemic autoimmune disorder characterized by exocrine gland dysfunction and lymphocytic infiltration, leading to dry mouth and eyes. Increasing evidence implicates extracellular vesicles, particularly exosomes, as critical mediators of immune regulation in pSD. This review outlines the biogenesis, molecular composition, and immunomodulatory functions of exosomes, and summarizes their emerging roles in the pathogenesis, diagnosis, and potential treatment of pSD.

Integrative genomic and single-cell framework identifies druggable targets for colorectal cancer precision therapy.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Despite therapeutic advances, there is a critical need to identify novel, effective, and safe drug targets to improve precision treatment strategies.

Methods: We developed a multi-layered framework integrating Mendelian randomization (MR), colocalization analysis, genome-wide association study (GWAS) data, and expression quantitative trait loci (eQTLs) to prioritize causal and druggable genes in CRC.

Integrative in silico analysis of per- and polyfluorinated alkyl substances (PFAS)-associated molecular alterations in human cancers: a multi-cancer framework for predicting toxicogenomic disruption.

Background: Per- and polyfluorinated alkyl substances (PFAS) are persistent environmental pollutants with known bioaccumulation potential and growing evidence of an association with cancer risk. However, the molecular mechanisms potentially linking PFAS exposure to carcinogenesis remain poorly understood. This study integrates computational toxicology and bioinformatics approaches to explore how PFAS-related molecular targets and pathways may overlap with those altered in six cancer types: breast carcinoma, kidney renal clear cell carcinoma, liver hepatocellular carcinoma, prostate adenocarcinoma, thyroid cancer, and uterine corpus endometrial carcinoma, all of which have been previously implicated in PFAS-related research.

Analyzing the potential targets and mechanism of per- and polyfluoroalkyl substances (PFAS) on breast cancer by integrating network toxicology, single-cell sequencing, spatial transcriptomics, and molecular simulation.

Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent environmental contaminants linked to adverse health effects, including an increased risk of breast cancer. However, the molecular mechanisms through which PFAS contribute to breast cancer development remain poorly understood. In this study, we employed an integrated approach combining network toxicology, single-cell sequencing, spatial transcriptomics, and molecular simulation to investigate the effects of PFAS on breast cancer.

Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation.

Background: Chaperonin containing TCP1 subunit 5 (CCT5), a vital component of the molecular chaperonin complex, has been implicated in tumorigenesis, cancer stemness maintenance, and therapeutic resistance. Nevertheless, its comprehensive roles in pan-cancer progression, underlying biological functions, and potential as a predictor of immunotherapy response remains poorly understood.

Methods: We performed a comprehensive multi-omics pan-cancer analysis of CCT5 across 33 cancer types, integrating bulk RNA-seq, single-cell RNA-seq (scRNA-seq), and spatial transcriptomics data.

Decoding per- and polyfluoroalkyl substances (PFAS) in hepatocellular carcinoma: a multi-omics and computational toxicology approach.

Background: Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are synthetic chemicals known for their widespread use and environmental persistence. These compounds have been increasingly linked to hepatotoxicity and the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms by which PFAS contribute to HCC remain underexplored.

Prioritizing endocrine-disrupting chemicals targeting systemic lupus erythematosus genes via Mendelian randomization and colocalization analyses.

Background: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease, with both genetic and environmental influences contributing to its development. Among environmental factors, endocrine-disrupting chemicals (EDCs), present in plastics, pesticides, and personal care products, have been implicated in immune disruption. This study investigated the interactions between EDCs and SLE-associated genes to elucidate their role in SLE susceptibility.

Global, regional and country burden of high BMI-related liver cancer among individuals aged above 70: trends from 1990 to 2021 and projections to 2044.

Background: Liver cancer (LC) is a major global health concern, being the fourth leading cause of cancer-related mortality. Older adults are more susceptible, though mortality rates for those over 70 are declining. However, disability from non-communicable diseases remains high.

Immunocyte phenotypes and childhood disease susceptibility: insights from bidirectional Mendelian randomization and implications for immunomodulatory therapies.

Immune cells are essential for maintaining immune homeostasis during childhood and influence both growth and disease susceptibility. However, the causal relationships between immunocyte phenotypes and childhood diseases remain unclear. This study employed a two-sample Mendelian Randomization (MR) analysis to assess causal associations between 731 immunocyte phenotypes and four major childhood diseases: childhood obesity, childhood absence epilepsy, childhood asthma, and childhood allergies.

Identification of as a Key Biomarker Linking Iron Metabolism and Dendritic Cell Activation in Systemic Lupus Erythematosus Through Bioinformatics and Experimental Validation.

Background: Systemic lupus erythematosus (SLE) is characterized by aberrant immune activation and disrupted iron metabolism, yet the molecular mediators that govern both processes remain unclear. This study aims to identify pivotal genes that modulate immune responses and iron metabolism, and to delineate their contributions to SLE pathogenesis.

Methods: Differentially expressed genes related to iron metabolism (IM-DEGs) were identified using datasets (GSE72326, GSE110169, GSE126307, and GSE50772) from the GEO database and the MSigDB.

Investigating the complex roles of immunocyte phenotypes in the pathogenesis of dermatitis: a causal inference Mendelian randomization analysis.

The etiology of dermatitis involves complex interactions between immune cells, genetics, and environmental factors. While immunocyte phenotypes have been linked to various forms of dermatitis, their causal role remains unclear. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal effects between 731 immunocyte phenotypes and four types of dermatitis: atopic dermatitis, contact dermatitis, infective dermatitis, and seborrhoeic dermatitis.

Prioritization of potential drug targets in ovarian-related diseases: Mendelian randomization and colocalization analyses.

Objective: To identify key genes and potential drug targets for ovarian-related diseases through genome-wide Mendelian randomization (MR) and colocalization analyses.

Design: We conducted a comprehensive two-sample MR analysis to estimate the causal effects of blood expression quantitative trait loci (eQTLs) on ovarian-related diseases, followed by colocalization analyses to verify the robustness of the expression instrumental variables (IVs). Phenome-wide association studies (PheWAS) were also performed to evaluate the horizontal pleiotropy of potential drug targets and possible side effects.

Genetic insights into the immunological basis of male infertility: a translational perspective.

Objective: To elaborate the causal relationships between specific immunocyte phenotypes and male infertility.

Design: Mendelian randomization using genome-wide association study data.

Subjects: Large cohorts of European ancestry.

Exploring the molecular mechanism of Tripterygium Wilfordii Hook F in treating systemic lupus erythematosus via network pharmacology and molecular docking.

Background: Tripterygium wilfordii Hook F (TwHF) is a prominent Chinese herbal formula. It exhibits significant clinical efficacy in treating systemic lupus erythematosus (SLE), though its mechanisms remain unclear. Our study employs network pharmacology and molecular docking to explore active compounds of TwHF and their associated targets for SLE treatment.

Analysis of toxicity and mechanisms of busulfan in non-obstructive azoospermia: A genomic and toxicological approach integrating molecular docking, single-cell sequencing, and experimentation in vivo.

Environmental pollutants, including chemical contaminants, heavy metals, and pesticides, have been linked to adverse effects on male reproductive health, particularly sperm quality. Non-obstructive azoospermia (NOA) is a severe form of male infertility caused by intrinsic testicular dysfunction, leading to a complete absence of sperm in the ejaculate. Busulfan, an alkylating chemotherapeutic agent widely used to treat chronic myelogenous leukemia, is known to induce NOA through its toxic effects on spermatogonial stem cells (SSCs).