Diastolic and systolic blood pressure and gout: a Mendelian randomization study.

Background: Although there is solid epidemiological evidence supporting the connection between hypertension and gout, little has been said about the relationship between diastolic and systolic blood pressure and gout, the causal relationship and direction associated are uncertain, so we aim to research the causal relationship between diastolic and systolic blood pressure and gout. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect between 2 blood pressure phenotypes (including diastolic blood pressure and systolic blood pressure) and 5 gout phenotypes (including gout, drug-induced gout, idiopathic gout, unspecified gout, and strictly defined gout) using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. Results: After the screening, we found a causal relationship between diastolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout, and a causal relationship between systolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout. Conclusion: From a genetic predisposition, controlling blood pressure may reduce the risk of gout.

Combining lipidomics and efficacy-oriented compatibility revealed that Qi Ge decoction compatibility improved lipid metabolism in hyperlipidemic rats.

The mechanism underlying traditional Chinese medicine (TCM) compatibility is difficult to understand. This study combined lipidomics and efficacy-oriented compatibility to explore underlying compatibility mechanisms of Qi Ge decoction (QG) for improving lipid metabolism in hyperlipidemic rats. The QG was divided into three groups according to the efficacy group strategy: the Huangqi-Gegen (HG), Chenpi (CP), and QG groups. Hyperlipidemic rats were treated with QG, HG, CP, or atorvastatin for 3 weeks. The mass spectral data of widely targeted lipidomics were used to evaluate lipid changes. Principal component analysis and orthogonal partial least squares discriminant analysis were used to assess the lipidomic differences between the groups. MetaboAnalyst 5.0 was used to explore metabolic pathways. Compared with the model group, serum cholesterol, triglyceride, and hepatic steatosis were significantly reduced by QG, whereas HG and CP had no significant effects on these indexes. Lipidomics showed that QG, HG, and CP back-regulated 60, 11, and 14 lipids, respectively. Compared with HG and CP, QG had more metabolic targets in diglycerides, triglycerides, ceramides, and phosphatidylethanolamines. Pathway analysis indicated that QG mainly regulated glycerophospholipid and glycerolipid metabolism. This study provided a new method of combining lipidomics and efficacy-oriented compatibility for exploring the scientific connotation of TCM compatibility.

Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing as obesity and diabetes become more common. There are no drugs approved for NAFLD yet. Qige decoction (QGD), a traditional Chinese medicine (TCM) formula, is used for NAFLD and hyperlipidemia treatment in TCM and has shown hypolipidemic and hepatoprotective effects. This study tried to interpret the pharmacology and molecular mechanisms of QGD in NAFLD rats. Firstly, the therapeutic effects of QGD on high-fat diet (HFD)-induced NAFLD rats were evaluated. Then, integration of lipidomics and transcriptomics was conducted to explore the possible pathways and targets of QGD against NAFLD. QGD at low dosage (QGL) administration reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) (P < 0.05). Liver histopathology indicated that QGL could alleviate hepatic steatosis. The main differential lipids (DELs) affected by QGD were glycerolipids. KEGG enrichment analysis suggested that the main pathways by which QGD improved NAFLD may be cholesterol metabolism, glycerolipid metabolism, and insulin resistance. Transcriptome sequencing identified 179 upregulated and 194 downregulated mRNAs after QGD treatment. An interaction network based on DELs and differential genes (DEGs) suggested that QGD inhibited hepatic steatosis mainly by reducing hepatic insulin resistance and triglyceride biosynthesis via the PPP1R3C/SIK1/CRTC2 and PPP1R3C/SIK1/SREBP1 signal axis, respectively. These findings indicated that QGD could protect against NAFLD induced by HFD. The improvement of hepatic insulin resistance and the reduction of triglyceride biosynthesis might be the potential mechanisms.

The efficacy and safety of acupuncture in nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The aim of this study was to determine the efficacy and safety of acupuncture treatment (AT) or acupuncture plus conventional medicine (CM) versus CM alone using a meta-analysis of all published randomized controlled trials (RCTs) for nonalcoholic fatty liver disease (NAFLD). METHODS: Eight databases were searched independently from inception to April 30, 2020. RCTs were included if they contained reports on the use acupuncture or the use of acupuncture combined with CM and compared with the use of CM. Summary odds ratio (OR) and 95% confidence intervals (CIs) were used to calculate the overall clinical efficacy. Secondary outcomes, namely aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index, were calculated by mean difference with 95% CIs. RESULTS: After the final screening, 8 RCTs with 939 patients were included. This meta-analysis showed that AT was superior to CM in improving overall clinical efficacy (OR = 3.19, 95% CI: 2.06-4.92, P  < .00001). In addition, AT plus CM could significantly improve overall clinical efficacy compared to treatment with CM alone (OR = 5.11, 95% CI: 2.43-10.75, P  < .0001). Moreover, the benefits were also demonstrated in other outcomes, including alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol indexes. However, AT plus CM could not decrease body mass index levels in comparison with CM. The safety profile of Acupuncture therapy was satisfactory. Taichong, Zusanli, Fenglong, and Sanyinjiao were major acupoints on NAFLD treatment. CONCLUSION: Acupuncture may be effective and safe for treatment of NAFLD. However, due to insufficient methodological quality and sample size, further high-quality studies are needed.

PET-CT and RNA sequencing reveal novel targets for acupuncture-induced lowering of blood pressure in spontaneously hypertensive rats.

Manual acupuncture (MA) can be used to manage high blood pressure; however, the underlying molecular mechanism remains unknown. To explore the mechanism of acupuncture in the treatment of hypertension, Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were subjected to either MA stimulation or the corresponding sham procedure as a negative control (Sham-MA) for 1 week. PET-CT scans, transcriptomics and molecular biology were used to evaluate the effect of MA. The results show that MA can regulate blood pressure in SHRs, change the glucose metabolism of the paraventricular hypothalamus (PVH), and affect the mRNA and protein expression levels of differentially expressed genes in the PVH. These genes may lower blood pressure by regulating angiotensin, endothelial function and inflammation. These findings reveal that MA regulates multiple biological processes and genes/proteins of the PVH, and provide a solid theoretical basis for exploring the mechanisms by which MA regulates hypertension.

Fatty Acid Metabolism in Immune Cells: A Bioinformatics Analysis of Genes Involved in Ulcerative Colitis.

Many immune cells participate in the pathogenesis of ulcerative colitis (UC), and fatty acid metabolism (FAM) is reported to supporting their cell-specific functions and proliferation, but the underlying mechanism is unclear. This study aimed to investigate the relationship between FAM and inflammation in colon tissues and identify potential therapeutic targets for regulating immune response. A total of 870 different expression genes (DEGs), 304 immunity-related DEGs, and 11 FAM-related DEGs were obtained, gene ontology analysis results showed that immune DEGs were significantly enriched in neutrophil migration, positive regulation of T cell activation. Fifteen types of immune cells were identified in inflamed colon tissues. Five FAM-related DEGs (ACOX1, ACSL4, ELOVL5, FADS2, and SCD) were highly correlated with immunity-related DEGs, and ACSL4, ELOVL5, and FADS2 were significantly upregulated in immune cells, while SCD is downregulated. Five FAM-related DEGs were highly correlated with immune cells. The study promotes the understanding of the pathogenesis of FAM in UC immune cells.

Ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats by suppressing inflammation and oxidative stress.

Several studies have demonstrated the chemopreventive role of ketoconazole in animal models of liver injury. However, the underlying molecular mechanisms of this hepatoprotective effect are poorly understood. The present study assessed the potential of ketoconazole to enhance resistance to carbon tetrachloride-induced hepatotoxicity in vivo in a rat model. Ketoconazole pretreatment adult male rats were intraperitoneally injected with carbon tetrachloride for 24 hr and various hepatic parameters were analyzed. We observed decreased serum transaminases activity, reduced nuclear RelA/p65 expression, and suppressed production of pro-inflammatory cytokines in the liver tissue. Histopathological examination demonstrated ketoconazole pretreatment to extensively prevent liver injury. In addition, it significantly increased nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) protein expression, glutathione (GSH) to oxidized glutathione (GSSG) ratio, and antioxidant enzymes gene expression. These results suggest that ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats, signifying its anti-inflammatory and antioxidant functions.

CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway.

Qi-Ge decoction (QGD), which is derived from the Huangqi Gegen decoction, contains three traditional Chinese herbs: Astragalus membranaceus (Huangqi), Pueraria lobata (Gegen), and Citri Reticulatae Blanco Pericarpium (Chenpi). Gastric mucosal damage caused by ethanol was prevented and alleviated by QGD. However, the role of QGD in protecting the liver from toxins has not been reported. High-performance liquid chromatography with diode-array detection was used to qualitatively analyze QGD. Positive control (silymarin 100 mg/kg/day), QGD (20, 10, or 5 g/kg/day), and Nrf2 inhibitor brusatol (0.4 mg/kg/2 d) were administered to rats for 7 days, and then, liver injury was induced by injecting 2 mL/kg 25% CCl4. After 24 h, blood and liver were collected for analysis and evaluation. QGD was found to contain 12 main components including calycosin, puerarin, and hesperidin. QGD treatment significantly reduced liver damage and decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities. QGD increased superoxide dismutase and catalase activities, and glutathione levels, but decreased malondialdehyde levels in livers from CCl4-treated rats. Compared to rats treated with CCl4 alone, after QGD administration, mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 were increased, while those of Kelch-like ECH-related protein 1 (Keap1) and cytochrome P450 (CYP)2E1 were decreased. However, these improvements in QGD were reversed by brusatol. In conclusion, QGD can achieve its hepatoprotective effect through an antioxidant mechanism by activating the Nrf2 pathway.