Overexpression of METTL14 mediates steatohepatitis and insulin resistance in mice.

Background: Lipid accumulation and redox imbalance, resulting from dysregulation of hepatic fatty acids oxidation, contribute to the development of steatohepatitis and insulin resistance. Recently, dysregulated RNA N6-methyladenosine (m6A) methylation modification has been found involving fatty liver. However, the role of methyltransferase-like 14 (METTL14), the core component of m6A methylation, in the development of steatohepatitis is unknown. Herein, we aimed to explore the role of METTL14 on steatohepatitis and insulin resistance in mice with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: The liver tissues of mice and patients with MASLD were collected to detect the expression of METTL14. METTL14 overexpression and METTL14 silence were used to investigate the effect of METTL14 on lipid metabolism disorder in vivo and in vitro. Knockout of METTL14 in primary hepatocytes was used to investigate the role of Sirtuin 1 (SIRT1) on lipid accumulation induced by METTL14. Results: METTL14 was dramatically up-regulated in the livers of db/db mice, high-fat diet (HFD)-fed mice, and patients with MASLD. METTL14 overexpression exacerbated MASLD and promoted lipid metabolism disorder and insulin resistance in mice. Conversely, METTL14 knockout ameliorated lipid deposition and insulin resistance in HFD-fed mice. Furthermore, METTL14 overexpression facilitated lipid accumulation, while METTL14 knockout reduced lipid accumulation in HepG2 cells and primary hepatocytes. In addition, METTL14 lost up-regulated SIRT1 expression in hepatocytes. SIRT1 deficiency abrogated the ameliorating effects of METTL14 downregulation in MASLD mice. Conclusions: These findings suggest that dysfunction of the METTL14-SIRT1 pathway might promote hepatic steatosis and insulin resistance.

[Sentinel lymph node mapping in colorectal cancer: study of 45 cases].

OBJECTIVE: To discuss the sentinel lymph node (SLN) mapping technique in colorectal cancer and its feasibility and utility. METHODS: The dye lymphazurin was injected subserosally around the tumor during operation in 43 colorectal cancer, 20 males and 25 females, aged 49.5 (27 - 72) so as to find the SLNs. Fast-frozen pathology and routine pathology were performed too. RESULTS: SLN was successfully identified in 42 of the 45 patients, with a successful biopsy rate of 93.3%. In these 45 patients, there were 250 lymph nodes examined, of which 52 nodes were identified as SLNs. The sensitivity was 90.4% (20/22), the specificity was 95.2% [(20 + 20)/42], and the false negative rate was 15% (3/20). CONCLUSION: SLN mapping in colorectal cancer plays an important role in diagnosing metastasis of lymph nodes, and can be used to direct the clinical surgery.