Ubiquitin-proteasome system: a potential participant and therapeutic target in antiphospholipid syndrome

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

Published: Feb. 18, 2025

APS (antiphospholipid syndrome) is an autoimmune disease characterized by thrombosis, pregnancy complications and persistent elevation of aPLs antibodies). Dysfunction innate immune cells, ECs (endothelial cells), platelets trophoblast cells are central to the development APS. The UPS (ubiquitin-proteasome system) a highly conserved post-translational modification in eukaryotes. Imbalance potentially disrupts protein homeostasis network provokes prothrombotic proinflammatory signaling during progression. In vivo, low-dose proteasome inhibitors believed effectively inhibit production factors clinical manifestations this review, we would like summarize likely contribution dysregulated pathogenesis Given significant progress made understanding molecular mechanisms how alterations lead diseases, targeting may represent novel therapeutic strategy.

Language: Английский

---

Unraveling the causal relationship and underlying mechanisms between cathepsins on liver cancer: findings from mendelian randomization and bioinformatics analysis

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are two major types of primary liver cancer (PLC). Earlier research has indicated a potential link between cathepsins cancer. Nonetheless, there have been limited clinical trials examining the connection PLC. Therefore, we conducted two-sample Mendelian randomization (MR) study to evaluate causal relationship Data from genome-wide association studies (GWAS) focusing on was collected. Additionally, summary data for GCST90018803 (Hepatic bile duct cancer, HBDC), GCST90018858 (related hepatic HC), were employed in discovery validation phases study, respectively. The inverse variance weighted (IVW) method served as analytical our supplemented by MR-Egger, median, simple mode, mode methods. To assess heterogeneity pleiotropy, MR-Egger intercept test, Cochran's Q well MR-Pleiotropy RESidual Sum Outlier (MR-PRESSO) analysis, along with leave-one-out analysis. After that, bioinformatic analysis based Gene Expression Omnibus (GEO) databases utilized, ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) functional enrichment utilized exploring underlying mechanisms. protein-protein docking confirm interaction related proteins. results showed that cathepsin F (CTSF), causally associated HBDC. CTSF decrease risk HBDC (OR = 0.826, 95% CI 0.711-0.959, P 0.012). may play protective roles patients No or pleiotropy observed. expression genes is lower HBDC, GO KEGG revealed mainly cell cycle, P53 pathway Docking had good binding ability MDM2, most well-established negative regulator p53. This provided new evidence suggesting plays an inhibition role progression. could be novel effective way HDBC treatment.

Language: Английский

---

Causal relationship and mediation effects of immune cells and plasma metabolites in atopic dermatitis: A Mendelian randomization study

Medicine, Journal Year: 2024, Volume and Issue: 103(41), P. e39932 - e39932

Published: Oct. 11, 2024

Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex etiology involving genetic, environmental, and immunological factors. This study employs Mendelian randomization to explore the causal relationships between immune cell phenotypes AD, mediating effects of plasma metabolites. Using data from European cohorts, we identified 7 significantly associated AD. Mediation analysis revealed that alpha-ketobutyrate 4-methyl-2-oxopentanoate ratio negatively regulates CCR2 on monocytes, while glycerol carnitine positively HLA-DR CD14− CD16− cells. These findings underscore critical role metabolic pathways in modulating responses suggest potential dietary therapeutic interventions for AD management. Further research should consider more diverse populations validate these findings.

Language: Английский

---

Causal Relationship and Potential Common Pathogenic Mechanisms Between Alopecia Areata and Related Cancer

Clinical Cosmetic and Investigational Dermatology, Journal Year: 2024, Volume and Issue: Volume 17, P. 2911 - 2921

Published: Dec. 1, 2024

Alopecia areata (AA) is an autoimmune skin disease. Observational studies have reported association between AA and cancer. However, the causal relationship cancer has not been reported. We employed a two-sample Mendelian randomization (MR) study to assess causality 17 subtypes of cancers.

Language: Английский

---