m6A RNA Methylation and Implications for Hepatic Lipid Metabolism.

This review presents a summary of recent progress in research on the N6-methyladenosine (m6A) modification and regulatory roles in hepatic lipid metabolism. As the most abundant internal modification of eukaryotic RNA, the m6A modification is a dynamic and reversible process of the m6A enzyme system, which includes writers, erasers, and readers. m6A methylation depressed lipid synthesis and facilitated lipolysis in liver. The depletion of m6A methyltransferase Mettl14/Mettl3 raised fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1), acetyl-CoA carboxylase (ACC), and elongase of very long chain fatty acids 6 (ELOVL6) in rodent liver, causing increases in liver weight, triglyceride (TG) production, and content in hepatocytes. FTO catalyzed m6A demethylation and the suppression m6A reader YTHDC2 promoted hepatocellular TG generation and hepatic steatosis in C57BL/6 mice through sterol regulatory element-binding protein 1c (SREBP-1c) signaling pathway, which upregulated the lipogenic genes FAS, SCD1, ACC, recombinant acetyl coenzyme a carboxylase alpha, and cell death-inducing DNA fragmentation factor-like effector C (CIDEC). Furthermore, FTO overexpression did not only enhance mitochondrial fusion to impair mitochondrial function and lipid oxidation but also promoted lipid peroxidation, accompanied by excessive TG in hepatocytes and rodent liver. Elevated m6A modification potently suppressed hepatic lipid accumulation, while the shrinkage of m6A modification arose hepatic lipid deposition. These findings have highlighted the beneficial role of m6A RNA methylation in hepatic lipid metabolism, potentially protecting liver from lipid metabolic disorders.

Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum. / çŽ‰ç«¹é»„é ®é€šè¿‡ä¿ƒè¿›HNF1b蛋白的SUMO化修饰抑制sortilinä»‹å¯¼çš„è„‚è´¨ç§¯ç´¯åŠåŠ¨è„‰ç²¥æ ·ç¡¬åŒ–.

This study aims to investigate the impact of hepatocyte nuclear factor 1ß (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.

[EFFECTIVENESS OF Ilizarov TECHNIQUE IN TREATMENT OF OLD DISLOCATION OF RADIAL HEAD].

OBJECTIVE: To explore the effectiveness of modified Ilizarov semi-ring external fixator combined with an ulnar osteotomy lengthening in the treatment of old dislocation of the radial head in children. METHODS: A retrospective analysis was made on the data of 14 patients with old dislocation of the radial head treated by the modified Ilizarov semi-ring external fixator combined with ulnar osteotomy lengthening between March 2012 and January 2015. The age ranged from 2 to 13 years (mean, 7.2 years), including 12 boys and 2 girls. There was 1 case of congential dislocation of the radial head and 13 cases of old Monteggia fracture. According to the Bado's classification, dislocation was rated as grade I in 12 cases and grade III in 2 cases. The elbow flexion-extension and forearm pronation and supination were compared between at pre- and post-operation; Mackay evaluation standard of elbow joint function was used to evaluate the effectiveness. RESULTS: The operation time ranged from 50 to 65 minutes (mean, 58 minutes). All patients were followed up 6-33 months (mean, 21 months). No complication of infection, myositis ossificans, or re-dislocation occurred. X-ray film showed bony healing at ulnar osteotomy site within 82-114 days (mean, 90 days). The elbow flexion-extension and forearm pronation and supination were significantly improved at postoperation when compared with preoperation (P < 0.05). The results of Mackay function assessment were excellent in 12 cases and good in 2 cases. CONCLUSION: The modified Ilizarov semi-ring external fixator combined with an ulnar osteotomy lengthening has the advantages of small incision, easy removal of fixator, satisfactory reduction, and no nonunion at ulnar osteotomy site in the treatment of old dislocation of the radial head, but the long-term effectiveness still needs to be followed up.