Identification of BAF60b as a chromatin remodeling checkpoint of diet-induced fatty liver disease.

Overnutrition has gradually become the primary causative factor of nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. Here, we identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complex and is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, while transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of PPARγ expression. Mechanistically, through motif analysis of liver ATAC-Seq and multiple validation experiments, we identified CCAAT/enhancer-binding protein ß (C/EBPß) as the transcription factor that interacts with BAF60b to suppress PPARγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work uncovers hepatic BAF60b as a negative regulator of liver steatosis through C/EBPß dependent chromatin remodeling.

Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis.

Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy. Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan. Methods: We conducted a systematic search (unlimited initial date to 22 October 2022) in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment. Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy (RR = 1.28, 95%CI:1.17 to 1.39), reduce blood pressure [systolic blood pressure (MD = 8.98, 95%CI:-12.38 to -5.59); diastolic blood pressure (MD = 5.74, 95%CI:-7.20 to -4.29)], serum creatinine (MD = -17.32, 95%CI:-20.55 to -14.10), blood urea nitrogen (MD = -1.89, 95%CI:-3.76 to -0.01), urine microalbumin (MD = -23.90, 95%CI:-26.54 to -21.26), and urinary protein to creatinine ratio (MD = -1.92, 95%CI:-2.15 to -1.69), cystatin C (MD = -1.04, 95%CI: -1.63 to -0.45) and increase calcitonin gene-related peptide (MD = 18.68, 95%CI:12.89 to 24.46) without increasing adverse reactions (RR = 2.20, 95%CI:0.52 to 9.40). But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low. Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256.

High serum uric acid levels may increase mortality and major adverse cardiovascular events in patients with acute myocardial infarction.

OBJECTIVES: To determine the validity of uric acid as a potential prognostic marker for long-term outcomes of patients with acute myocardial infarction (AMI) and those with AMI undergoing percutaneous coronary intervention (PCI). Methods: Systematic review and meta-analysis were performed. We retrieved data from retrospective and prospective cohort studies that investigated whether serum uric acid (SUA) level affects the prognosis of patients with AMI. RESULTS: Thirteen studies involving 9371 patients were included. High serum uric acid (HSUA) level increased mid/long-term mortality (risk ratio (RR)=2.32, 95% confidence intervals (CI): 2.00-2.70) and had higher short-term mortality (RR=3.09, 95% CI: 2.58-3.71), higher mid/long-term major adverse cardiovascular events (MACE) risk (RR=1.70, 95% CI: 1.54-1.88), and higher short-term MACE risk (RR=2.47, 95% CI: 2.08-2.92) for patients with AMI. In the PCI subgroup, the HSUA level also increased mid/long-term mortality (RR=2.33, 95% CI: 1.89 to 2.87) and had higher mid/long-term MACE risk (RR=1.64, 95% CI: 1.48-1.82), and higher short-term MACE risk (RR 2.43, 95% CI: 2.02-2.93) for patients who were treated with PCI after AMI. Particularly in the PCI subgroup, a higher short-term mortality (RR=6.70, 95% CI: 3.14-14.31) was presented in the group with lower HSUA cut-off level, and the mortality was higher than the group with higher HSUA cut-off level (RR=2.69, 95% CI: 2.09-3.46). Conclusion: The HSUA level significantly increased the mortality and MACE risk of patients with AMI. Mild elevation of SUA levels (normal range) have started to have a significant impact on the short-term mortality of patients who underwent PCI, and has not received the attention of previous studies. However, this condition should be further investigated.