Molecular crosstalk and potential causal mechanisms of rheumatoid arthritis and sarcopenia co-morbidity: A gene integration analysis

Experimental Gerontology, Journal Year: 2025, Volume and Issue: 203, P. 112729 - 112729

Published: March 11, 2025

Rheumatoid arthritis (RA) promotes the onset and progression of sarcopenia, yet mechanisms co-morbidity between RA sarcopenia are under-explored. Therefore, this study integrated Gene Expression Omnibus (GEO) Genome-wide association studies (GWAS) data to comprehensively identify shared genes, associated mechanisms, biological pathways in sarcopenia. Utilizing two GEO datasets-GSE226151, which includes 60 RNA-seq samples skeletal muscle from healthy aged, pre-sarcopenia, individuals, GSE55235, with 20 synovial tissue joints-we performed differentially expressed genes analysis, weighted gene co-expression network analysis crosstalk enrichment for these genes. Using relevant GWAS datasets, SMR analyses cis-eQTL were performed. We further validated identified key explored potential causal associations sarcopenia-related traits. 25 involved immune-inflammatory response pathways, including neutrophil extracellular trap formation Fc gamma receptor-mediated phagocytosis. six core genes: NCF1, FCGR2A, FCGR3A, SORL1, FCGR3B, ITGAX (PSMR < 0.05). showed that FCGR2A might have a negative appendicular lean mass, whole body fat-free positive (P Overall, is first reveal molecular identifying response-related pathways. Further conducted validate emerging as drug target RA-associated These findings provide new insights into comorbid offering therapeutic targets both conditions.

Language: Английский

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The molecular subtypes of autoimmune diseases

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 1348 - 1363

Published: March 28, 2024

Autoimmune diseases (ADs) are characterized by their complexity and a wide range of clinical differences. Despite patients presenting with similar symptoms disease patterns, reactions to treatments may vary. The current approach personalized medicine, which relies on molecular data, is seen as an effective method address the variability in these diseases. This review examined pathologic classification ADs, such multiple sclerosis lupus nephritis, over time. Acknowledging limitations inherent classification, focus shifted achieve deeper insight into heterogeneity. study outlined established methods findings from categorizing systemic erythematosus (SLE) four subtypes, inflammatory bowel (IBD) two, rheumatoid arthritis (RA) three, (MS) single subtype. It was observed that high inflammation subtype IBD, RA subtype, MS "inflammation & EGF" share similarities. These subtypes all display consistent pattern primarily driven activation JAK-STAT pathway, drugs being those target this signaling pathway. Additionally, identifying markers uniquely associated various within same disease, able describe differences between detail. expected contribute development treatment plans for establish strong basis tailored approaches treating autoimmune

Language: Английский

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SLC6A14 as a Key Diagnostic Biomarker for Ulcerative Colitis: An Integrative Bioinformatics and Machine Learning Approach

Biochemical Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Language: Английский

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Neutrophils: From Inflammatory Bowel Disease to Colitis-Associated Colorectal Cancer

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 925 - 947

Published: Jan. 1, 2025

Inflammatory bowel disease (IBD) is a non-specific inflammatory of digestive tract, primarily manifesting as ulcerative colitis (UC) and Crohn's (CD). The precise etiology IBD remains elusive. interplay genetic factors, environmental influences, intestinal microbiota contributes to the establishment an uncontrolled immune environment within intestine, which can progressively lead atypical hyperplasia ultimately malignancy over long period. This colorectal malignant tumor that arises from chronic referred colitis-associated cancer (CAC). Dysregulation in quantity functionality neutrophils plays significant role onset, progression, recurrence IBD, well transition CAC. Neutrophils affect pathophysiology through various mechanisms, including production reactive oxygen species (ROS), degranulation, release mediators chemokines, formation neutrophil extracellular traps (NETs). These processes induce DNA mutations, thereby facilitating development colon cancer. Given incomplete understanding mechanisms underlying CAC, effective treatment prevention strategies remain challenging. Consequently, comprehensive review functional roles CAC essential for advancing our pathogenesis identifying potential therapeutic targets.

Language: Английский

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From ulcerative colitis to metastatic colorectal cancer: The neutrophil contribution

American Journal Of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Intranasal delivery of hMSC-derived supernatant for treatment of ischemic stroke by inhibiting the pro-inflammatory polarization of neutrophils

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Stem cells utilized for ischemic stroke treatment often display unstable homing capabilities and diminished activity in vivo, limiting their neuroprotective efficacy. Furthermore, the optimal delivery route stem remains undetermined. While cytokines secreted by show promise modulating post-stroke inflammation, direct application of these supernatants underlying mechanisms are still unclear. Secretory (hMSC-L) cell lysate products (hMSC-M) from primary human umbilical cord mesenchymal cells-cultured medium were administered intranasally to mice with cerebral ischemia. The effects hMSC-L hMSC-M assessed TTC staining, behavioral tests pathological staining. Flow cytometry qPCR evaluated expression immune CNS peripheral organs. In vitro, flow ELISA measured on N2 polarization inflammatory murine neutrophils. Western blot analysis determined impact PPAR-γ/STAT6/SOCS1 pathway, which is crucial neutrophil polarization. experiments, assessments reveal intranasal significantly reduces infarct volume ischemia, improves neurological function scores, promotes motor recovery. Higher concentrations contributed a more pronounced effect neuropathological improvements mice. Intranasal infiltration brain increases proportion anti-inflammatory N2-subtype neutrophils, boosting levels IL-10 TGF-β. vitro experiments demonstrate that promote nuclear translocation PPAR-γ neutrophils stimulated PMA, activating downstream STAT6/SOCS1 signaling pathway encourage effectively ameliorates injury mice, comparable traditional administration routes like intravenous delivery. Treatment enhances neuroinflammatory response increasing infiltration. These results provide theoretical basis deeper understanding therapy exploring suitable pathways treatment.

Language: Английский

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Protective effect of Dendrobium officinale extract on aspirin-induced gastric lesions in rats

Molecular Immunology, Journal Year: 2025, Volume and Issue: 179, P. 42 - 51

Published: Feb. 6, 2025

To examine the protective effect and mechanism of original extract Dendrobium officinale (DE) on gastric lesions caused by aspirin (ASA) facilitate development traditional Chinese medicine products. In this study, a rat model was established, then rats were treated with DE for 5 days. We found that ASA-induced mucosal detachment hemorrhagic in improved after supplementation. Meanwhile, effectively inhibits secretion inflammatory mediators (IL-6, IL-1β, TNF-α, MPO, COX-2) upregulates activity antioxidant core components (T-SOD, GSH-Px) defense factors (TFFs, EGF, EGFR) tissues. It further exerted defensive mucosa association NF-κB/Nrf-2/HO-1 signaling. conclusion, protects from oxidative stress, improves its defenses, as well being potential nutrient future, preventing lesions.

Language: Английский

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Neutrophils in colorectal cancer: mechanisms, prognostic value, and therapeutic implications

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Neutrophils, the most abundant myeloid cells in human peripheral blood, serve as first defense line against infection and are also significantly involved initiation progression of cancer. In colorectal cancer (CRC), neutrophils exhibit a dual function by promoting tumor events exerting antitumor activity, which is related to heterogeneity neutrophils. The neutrophil extracellular traps (NETs), gut microbiota, various within microenvironment (TME) shaping heterogeneous This article provides an updated overview complex functions underlying mechanisms CRC their pivotal role guiding prognosis assessment therapeutic strategies, aiming offer novel insights into neutrophil-associated treatment approaches for CRC.

Language: Английский

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MPO and its role in cancer, cardiovascular and neurological disorders: an update

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 755, P. 151578 - 151578

Published: March 2, 2025

Language: Английский

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The intervention of NLRP3 inflammasome inhibitor: oridonin against azoxymethane and dextran sulfate sodium–induced colitis-associated colorectal cancer in male BALB/c mice

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

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