Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis

AbstractBackgroundRheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition.ObjectivesThe aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin.MethodsA total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits.ResultsThe CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis.ConclusionOur findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Polimorfismos dos genes metilenotetrahidrofolato redutase, fator de crescimento transformador β1 e linfotoxina‐α e susceptibilidade à artrite reumatoide

ResumoAntecedentesA artrite reumatoide é uma doença autoimune amplamente prevalente com sugerida predisposição genética.ObjetivosDetectar o padrão de polimorfismo dos genes metilenotetrahidrofolato redutase (MTHFR C677T e A1298C), fator de crescimento transformador β1 (TGF‐β1 T869C) e linfotoxina‐α (LT‐α A252G) em pacientes com artrite reumatoide e correlacionar esses padrões com a atividade da doença e os níveis séricos de fator de necrose tumoral alfa (TNF‐α), fator ativador de linfócitos B (BAFF) e osteopontina.MétodosForam genotipados 194 indivíduos – 90 controles e 104 com artrite reumatoide – à procura de polimorfismos dos genes MTHFR C677T e A1298C, TGF‐β1 T869C e LT‐α A252G com uma metodologia baseada na PCR‐RFLP. Mensuraram‐se também os níveis séricos de TNF‐α, osteopontina e BAFF com kits de Elisa.ResultadosO genótipo CT e o alelo T do MTHFR C677T e o genótipo GG e alelo G do LT‐α A252G estão associados ao risco de AR e a níveis mais elevados da citocina pró‐inflamatória TNF‐α em pacientes com artrite reumatoide.ConclusãoOs achados do presente estudo sugerem que há associação entre os polimorfismos dos genes MTHFR C677T e LT‐α A252G e um risco aumentado de AR nessa amostra da população egípcia.AbstractBackgroundRheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition.ObjectivesThe aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677T and A1298C), transforming growth factor‐β1 (TGF‐β1 T869C) and lymphotoxin‐α (LT‐α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor‐alpha (TNF‐α), B‐Cell Activating Factor (BAFF), and osteopontin.MethodsA total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677T and A1298C, TGF‐β1 T869C and LT‐α A252G polymorphisms using a methodology based on PCR‐RFLP. Also serum levels of TNF‐α, osteopontin and BAFF were measured by ELISA kits.ResultsThe CT genotype and T allele of MTHFR C677T and GG genotype and G allele of LT‐α A252G are associated with the risk of RA and with higher levels of the pro‐inflammatory cytokine, TNF‐α in patients with rheumatoid arthritis.ConclusionOur findings suggest that there is association between MTHFR C677T and LT‐α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis

ABSTRACT Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury—Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury

α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis

The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP < GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H&E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy