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Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by persistent mucosal inflammation. Oxidative stress plays a vital role in UC pathogenesis. Selenium (Se), an essential trace element, functions via selenoproteins and metabolites. Selenocysteine (Sec), the 21st amino acid, is incorporated into selenoproteins with strong antioxidant and anti-inflammatory properties. However, the role of selenium metabolism and selenoproteins (SeMet) in UC remains poorly understood.
Methods: Gene expression and clinical data from UC patients and healthy controls were obtained from the GEO database. SeMet-related gene sets were collected from Molecular Signatures Database (MSigDB). Weighted gene co-expression network analysis (WGCNA) and differential expression analysis identified key modules and genes associated with UC. Machine learning algorithms were used to screen signature genes and construct a UC risk prediction model. Single-cell RNA sequencing (scRNA-seq) was performed to examine gene expression at the cellular level. Expression of differentially regulated genes (DRGs) and signature genes was validated using quantitative polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry (IHC).
Results: DRGs were significantly upregulated in UC and used to classify 161 UC samples into two subtypes. Six candidate signature genes were identified by integrating WGCNA and machine learning, showing high diagnostic potential and inter-correlation. scRNA-seq revealed upregulation of many selenoproteins in epithelial cells and downregulation of SELENOP in immune cells. The six signature genes were consistently upregulated across multiple cell types. WARS1 (tryptophanyl-tRNA synthetase 1), one of the signature genes, responded strongly to oxidative stress, and its knockdown elevated inflammatory cytokine levels.
Conclusion: SeMet-related genes are crucial in UC pathogenesis, particularly through antioxidant defense and immune modulation. The identified six-gene signature offers promising diagnostic and therapeutic potential for UC.
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http://dx.doi.org/10.2147/JIR.S533743 | DOI Listing |
Urol Oncol
September 2025
Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. Electronic address:
Background: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy.
Methods: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients.
J Immunother Cancer
September 2025
Harold C Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.
Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.
Chem Biol Interact
September 2025
Department of Systems Medicine. School of Medicine. University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK.
Humans are exposed to mixtures of chemical pollutants from various environmental sources at all stages of life. Understanding how these compounds are causally linked to population health effects is challenging because of the ethical limitations on studying controlled human exposures and the complexity of the many potential molecular mechanisms involved. We hypothesized that studies using a combination of in vivo murine stress reporter models together with non-targeted global transcriptome analysis will define the toxic mechanisms of complex chemical mixtures in a physiological context.
View Article and Find Full Text PDFBiol Psychiatry
September 2025
Developmental Neuroscience and Neurogenetics Program, The Saban Research Institute, Los Angeles, CA; Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Canada; Division of Endocrinology, Children's Hospital LA, Los Angeles, CA; Department of Pediatrics, Keck Scho
Background: Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of psychosomatic disorders in adolescence and adulthood. Most investigations into biological processes that have been perturbed by ELA have profiled DNA methylation in whole blood and coalesced around perturbations of immunobiology being centrally insulted by ELA.
Methods: To identify novel molecular signatures that are enduringly perturbed by childhood maltreatment, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT, n = 7, 4M 3F) or maltreatment in infancy (MALT, n = 6, 3M 3F).
Brain Behav Immun
September 2025
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Biomedical Research Networking Center for Rare Diseases (CIBERER), Barcelona 08003, Spain.
Treatment-resistant depression (TRD) is a severe condition characterized by chronic and recurrent depressive symptoms, leading to significant morbidity and a considerable socio-economic impact. Genetic and biological studies suggest that TRD is associated with distinct biological characteristics. In this study, we analysed whole-transcriptome differences in 293 patients with major depressive disorder (MDD) to compare TRD (N = 150) vs non-TRD (N = 143) cases.
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