The Role and Mechanism of CREBH Regulating SIRT3 in Metabolic Associated Fatty Liver Disease.

AIMS: To investigate the effect of cAMP response element-binding protein H (CREBH) on metabolic associated fatty liver disease by regulating sirtuin 3 (SIRT3). MAIN METHODS: Two mouse models of fatty liver induced by a methionine-choline deficient (MCD) diet and a high-fat (HF) diet and an in vitro model of palmitic acid (PA) induced lipid-overloaded hepatocytes were constructed to detect the expression of CREBH, SIRT3, total acetylation, and downstream protein interactions and lipid metabolism phenotype, which were further validated in CREBH-/- mice and lentivirus-overexpressing CREBH hepatocytes. KEY FINDINGS: In fatty liver and lipid overload models, the expressions of CREBH and SIRT3 were down-regulated and their expression was positively correlated, accompanied by an increase in the level of total protein acetylation. Overexpression of CREBH alleviated excess lipid accumulation, impaired viability, and the ability to metabolize energy through the fatty acid oxidation pathway in hepatocytes in vitro. Furthermore, overexpression of CREBH restored the interaction of the deacetylase SIRT3 with the molecules carnitine palmitoyl-transferase 2 (CPT2) and long-chain acyl CoA dehydrogenase (ACADL) involved in the fatty acid oxidation pathway and their deacetylation status. However, CREBH-/- aggravated the damage of lipid metabolism in the liver tissue of mice. SIGNIFICANCE: CREBH increased the enzymatic activity of downstream factors by positively regulating the expression of SIRT3, which promoted the oxidative decomposition of fatty acids in hepatocytes and played an important role in fatty acid oxidation in MAFLD.

Changes of corneal anterior surface morphology and higher-order aberrations after Smart / 中华实验眼科杂志

Objective:To compare the changes of corneal asphericity and higher-order aberrations after smart pulse technology-assisted transepithelial photorefractive keratectomy (Smart) for low and moderate myopia and to investigate the changes in the shape of the front corneal surface in patients with different diopters.Methods:A non-randomized controlled study design was used.Ninety-eight eyes of 54 patients with moderate or low myopia who underwent Smart surgery in Tianjin Medical University Eye Hospital from November 2018 to March 2019 were included.The 41 eyes of 23 patients with low myopia were set as the low-myopia group, and 57 eyes of 31 patients with moderate myopia were assigned as the moderate-myopia group.The Pentacam anterior segment analysis system was used to measure Q value, index of surface variance (ISV), corneal higher-order aberration (HOA), corneal vertical coma (Z 3-1), corneal horizontal coma (Z 31) and spherical aberration (Z 40) before surgery, 1 month and 3 months after surgery.The anterior surface morphology was compared between the low-myopia and moderate-myopia group.Pearson correlation analysis was used to analyze the correlations between measurement parameters.The study protocol was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2019KY-17). Written informed consent was obtained from each patient before surgery. Results:Corneal Q value, ISV, HOA and Z 40 were 0.445±0.191, 26.973±5.611, 0.671±0.142 and 0.384±0.188, respectively, in the low-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.273±0.817, 13.784±2.376, 0.433±0.687 and 0.231±0.062 (all at P<0.05). Corneal Q value, ISV, HOA and Z 40 were 0.693±0.203, 34.038±5.773, 0.874±0.216 and 0.520±0.129, respectively, in the moderate-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.309±0.104, 14.838±3.992, 0.409±0.081 and 0.228±0.089 (all at P<0.05). Corneal Q values, ISV, HOA and Z 40 in the moderate-myopia group were higher than those in the low-myopia group at different time points after surgery, showing significant differences between the two groups (all at P<0.05). There was no significant difference in postoperative 1-month and 3-month corneal Z 3-1 and Z 31 between the two groups (both at P>0.05). The results of correlation analysis showed that there were no significant differences in ΔQ value and ΔISV between the two groups, both of which were negatively correlated with spherical equivalent (ΔQ value: low-myopia group: r=-0.364, P=0.044; moderate-myopia group: r=-0.589, P<0.01; ΔISV: low-myopia group: r=-0.298, P=0.039; moderate-myopia group: r=-0.409, P=0.022). ΔQ value and ΔZ 40 were positively correlated in the moderate-myopia group ( r=0.348, P=0.009); there was no significant correlation between ΔQ value and ΔZ 40 in the low-myopia group ( r=0.180, P=0.266). Conclusions:The corneal high-order aberrations and ISV after Smart are increased in comparison with preoperative values in the low-myopia and moderate-myopia eyes, and the corneal Q values change from negative to positive.The effect of Smart on corneal asphericity is less in the low-myopia eyes.