The Potential Influence of Immune Modulatory Molecules (TGF-βIII and CTLA-4) in Pathogenicity of PCOS DOI Creative Commons

Mustafa Riyadh Abdullah,

Hazima Mossa Alabassi

Karbala International Journal of Modern Science, Journal Year: 2024, Volume and Issue: 10(3)

Published: July 24, 2024

Polycystic ovary syndrome (PCOS) is characterised by chronic anovulation, hyperandrogenism, polycystic ovaries, and immunological dysregulation. Immune homeostasis inflammation management require immune functions. T-regulatory cells (Tregs) regulate PCOS's system, inflammation, insulin resistance, ovarian function, homeostasis. Transforming growth factor βIII (TGF-βIII) Cytotoxic-T-lymphocyte-associated-protein-4 (CTLA-4) receptors on the surfaces of Treg are important for controlling system. The study included 68 PCOS patients 22 non-PCOS women controls aged 20–45. waist-hip ratio (WHR) determines obesity. We evaluated serum levels gene expression TGF-βIII CTLA-4 via ELISA real-time PCR. Women with had significantly higher compared to controls. reveals a considerable increase in control. Compared controls, < > 25 TGF-III concentrations. According RT-PCR test, (> 25) much amounts than also increased WHR at 0.8 results showed that obese (>0.8) Based clinical signs, folding were who irregular periods whose cycles normal. These data indicate role etiology. This suggests targeting immunotherapy.

Language: Английский

Fibroblast growth factor receptor 3 mutation promotes HSPB6-mediated cuproptosis in hypochondroplasia by impairing chondrocyte autophagy DOI Creative Commons
Jing Chen, Dan He,

Chengrun Yuan

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 51, P. 68 - 81

Published: Feb. 4, 2025

Language: Английский

Citations

1
Characterizing mitochondrial features in osteoarthritis through integrative multi-omics and machine learning analysis DOI Creative Commons

Yinteng Wu,

Haifeng Hu, Tao Wang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 4, 2024

Purpose Osteoarthritis (OA) stands as the most prevalent joint disorder. Mitochondrial dysfunction has been linked to pathogenesis of OA. The main goal this study is uncover pivotal role mitochondria in mechanisms driving OA development. Materials and methods We acquired seven bulk RNA-seq datasets from Gene Expression Omnibus (GEO) database examined expression levels differentially expressed genes related utilized single-sample gene set enrichment analysis (ssGSEA), (GSEA), weighted co-expression network (WGCNA) analyses explore functional associated with these genes. Seven machine learning algorithms were identify hub mitochondria-related develop a predictive model. Further included pathway enrichment, immune infiltration, gene-disease relationships, mRNA-miRNA construction based on genome-wide association studies (GWAS) was performed using Atlas database. GSEA, variation (GSVA), protein analysis, WGCNA employed investigate relevant pathways subtypes. Harmonizome analyze across various human tissues. Single-cell data conducted examine patterns distribution pseudo-temporal changes. Additionally, real-time polymerase chain reaction (RT-PCR) used validate Results In OA, significantly activated. Nine (SIRT4, DNAJC15, NFS1, FKBP8, SLC25A37, CARS2, MTHFD2, ETFDH, PDK4) identified. They constructed models good ability predict These are primarily macrophages. Unsupervised consensus clustering identified two mitochondria-associated isoforms that metabolism. showed they all single cells varied cell differentiation. RT-PCR Conclusion SIRT4, PDK4 potential mitochondrial target for studying classification could help personalize treatment patients.

Language: Английский

Citations

4
Identification and validation of transcriptome-wide association study-derived genes as potential druggable targets for osteoarthritis DOI Creative Commons
Xindie Zhou, Xinjian Ye, Jiapei Yao

et al.

Bone and Joint Research, Journal Year: 2025, Volume and Issue: 14(3), P. 224 - 235

Published: March 13, 2025

Aims Osteoarthritis (OA) is a widespread chronic degenerative joint disease with an increasing global impact. The pathogenesis of OA involves complex interactions between genetic and environmental factors. Despite this, the specific mechanisms underlying remain only partially understood, hindering development targeted therapeutic strategies. Methods A transcriptome-wide association study (TWAS) was conducted for site-specific phenotypes using functional summary-based imputation (FUSION). High-confidence candidate genes were identified through rigorous quality control measures, including joint/conditional analysis, permutation tests, best model evaluation, colocalization analysis. Co-expression network analysis performed to elucidate biology these genes. Druggable gene targets their structural models retrieved from DrugBank SWISS-MODEL databases. Finally, enrichment mitogen-activated protein kinase 3 ( MAPK3 ) SMAD3 in validated biochemically vitro vivo models, as well human histological sections. Results Utilizing FUSION algorithm, TWAS 794 OA. After control, 14 classified high-confidence genes, seven recognized potential drug GCAT, MAPK3, MST1R, PFKM, RAD9A, SMAD3, USAP8 . revealed strong biological Both experiments demonstrated high activity enriched expression two Conclusion present tissue-specific druggable OA, providing new insights into landscape processes involved Further studies are warranted confirm findings. Cite this article: Bone Joint Res 2025;14(3):224–235.

Language: Английский

Citations

0
Fibroblast growth factor 8 (FGF8) induces mitochondrial remodeling in chondrocytes via ERK/AMPK signaling pathway DOI
Hongcan Huang, Mei-Ling Duan, Jieya Wei

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(7)

Published: March 31, 2025

Abstract Osteoarthritis (OA) is a disease characterized by articular cartilage degeneration, and its pathogenic mechanisms are associated with mitochondrial homeostasis disorders. Fibroblast growth factor 8 (FGF8) multipotent protein ligand which upregulated in OA cartilage. However, the molecular FGF8 regulates mitochondria chondrocytes not yet fully understood. Here, we treated detected effects of on morphology cytoplasm using transmission electron confocal laser scanning microscopy. ATP levels were measured to determine cellular energy status. Western blotting immunofluorescence staining experiments employed detect fusion‐fission proteins mitofusin 1 (MFN1), 2 (MFN2), optic atrophy (OPA1), dynamin‐related (DRP1), fission (FIS1), related signaling pathways. The FGF receptor (FGFR) inhibitor, AZD4547, ERK U0126, used verify specific FGFR We found that regulated dynamics inducing elongation. While it fusion MFN1, MFN2, OPA1, downregulated DRP1 FIS1. AMPK pathways activated after treatment. In contrast, both AZD4547 U0126 inhibitors abolished elongation as well alteration induced FGF8, also inhibited FGF8‐triggered activation AMPK. This study first reveal remodels through ERK/AMPK chondrocytes, offering novel insights into potential role OA.

Language: Английский

Citations

0
TGF‐β3 mediates mitochondrial dynamics through the p‐Smad3/AMPK pathway DOI Creative Commons

Xinmei Du,

Mengmeng Duan, Shiyi Kan

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 57(5)

Published: Nov. 27, 2023

Abstract It is well recognized that mitochondrial dynamics plays a vital role in cartilage physiology. Any perturbation could cause disorders metabolism and even lead to the occurrence of diseases such as osteoarthritis (OA). TGF‐β3, an important growth factor appears joints OA disease, shows its great potential chondrocyte metabolism. Nevertheless, TGF‐β3 on still not understood. Here we aimed investigate effect chondrocytes reveal underlying bio‐mechanism. By using transmission electron microscopy (TEM) for number morphology mitochondria, western blotting protein expressions, immunofluorescence cytoplasmic distributions proteins, RNA sequencing transcriptome changes related dynamics. We found increase mitochondria chondrocytes. TGF‐β3‐enhanced was via promoting fission. The fission induced by mediated AMPK signaling. activated canonical p‐Smad3 signaling resultantly AMPK‐induced Taken together, these results elucidate understanding provide cues therapeutic strategies injury disease terms energy

Language: Английский

Citations

6
The Potential Influence of Immune Modulatory Molecules (TGF-βIII and CTLA-4) in Pathogenicity of PCOS DOI Creative Commons

Mustafa Riyadh Abdullah,

Hazima Mossa Alabassi

Karbala International Journal of Modern Science, Journal Year: 2024, Volume and Issue: 10(3)

Published: July 24, 2024

Polycystic ovary syndrome (PCOS) is characterised by chronic anovulation, hyperandrogenism, polycystic ovaries, and immunological dysregulation. Immune homeostasis inflammation management require immune functions. T-regulatory cells (Tregs) regulate PCOS's system, inflammation, insulin resistance, ovarian function, homeostasis. Transforming growth factor βIII (TGF-βIII) Cytotoxic-T-lymphocyte-associated-protein-4 (CTLA-4) receptors on the surfaces of Treg are important for controlling system. The study included 68 PCOS patients 22 non-PCOS women controls aged 20–45. waist-hip ratio (WHR) determines obesity. We evaluated serum levels gene expression TGF-βIII CTLA-4 via ELISA real-time PCR. Women with had significantly higher compared to controls. reveals a considerable increase in control. Compared controls, < > 25 TGF-III concentrations. According RT-PCR test, (> 25) much amounts than also increased WHR at 0.8 results showed that obese (>0.8) Based clinical signs, folding were who irregular periods whose cycles normal. These data indicate role etiology. This suggests targeting immunotherapy.

Language: Английский

Citations

0