Chul Won Ahn

Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism.

Previous studies suggested that the hepatoprotective activity of betaine is associated with its effects on sulfur amino acid metabolism. We examined the mechanism by which betaine prevents the progression of alcoholic liver injury and its therapeutic potential. Rats received a liquid ethanol diet for 6 wk. Ethanol consumption elevated serum triglyceride and TNFα levels, alanine aminotransferase and aspartate aminotransferase activities, and lipid accumulation in liver. The oxyradical scavenging capacity of liver was reduced, and expression of CD14, TNFα, COX-2, and iNOS mRNAs was induced markedly. These ethanol-induced changes were all inhibited effectively by betaine supplementation. Hepatic S-adenosylmethionine, cysteine, and glutathione levels, reduced in the ethanol-fed rats, were increased by betaine supplementation. Methionine adenosyltransferase and cystathionine γ-lyase were induced, but cysteine dioxygenase was down-regulated, which appeared to account for the increment in cysteine availability for glutathione synthesis in the rats supplemented with betaine. Betaine supplementation for the final 2 wk of ethanol intake resulted in a similar degree of hepatoprotection, revealing its potential therapeutic value in alcoholic liver. It is concluded that the protective effects of betaine against alcoholic liver injury may be attributed to the fortification of antioxidant defense via improvement of impaired sulfur amino acid metabolism.

Atherogenic dyslipidemia promotes autoimmune follicular helper T cell responses via IL-27.

The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe–/– and Ldlr–/– mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe–/– mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c. Mechanistically, the atherogenic environment induced the cytokine IL-27 from dendritic cells in a Toll-like receptor 4 (TLR4)-dependent manner, which in turn triggered the differentiation of CXCR3+ TFH cells while inhibiting the differentiation of follicular regulatory T cells. Blockade of IL-27 signals diminished the increased TFH cell responses in atherogenic mice. Thus, atherogenic dyslipidemia augments autoimmune TFH cell responses and subsequent IgG2c production in a TLR4- and IL-27-dependent manner.Dyslipidemia and autoimmune disease are often associated. Chung and colleagues demonstrate a mechanistic pathway by which dyslipidemia leads to the induction of pathogenic autoantibodies.

Depletion of intracellular Homocysteine via up-regulation of Betaine-homocysteine methyltransferase is implicated in the anti-lipogenic effect of Betaine

A series of N,N’-disubstituted urea derivatives (1-10) were synthesized and their structures were elucidated on the basis of analytical and spectral (IR, 1H NMR) data. These synthesized compounds were assayed for their cytotoxicity against human breast cancer cell line (MCF-7) by using MTT assay with doxorubicin as a positive control. IC50 values for the tested compounds were higher than 50 μM except compound 8. Compound 8 displayed moderate antiproliferative activity against MCF-7 cell line (with IC50 value of 41.27 ± 5.14 μM). All of the compounds were also evaluated for their antimicrobial effects against Enterococcus hirae (ATCC 10541), Escherichia coli (ATCC 11229), Pseudomonas aeruginosa (ATCC 15442), Staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 10231). None of the compounds showed antimicrobial activity.