Causal relationship between atrial fibrillation and stroke risk: a Mendelian randomization.

OBJECTIVES: This study aimed to investigate the causal relationship between Atrial Fibrillation (AF) and the risk of Stroke using a Mendelian randomization (MR) approach. METHODS: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) summary statistics data. In this analysis, genetic variants associated with AF were used as instrumental variables to estimate the causal effect. The inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed for estimation. Additionally, sensitivity analysis was performed using the leave-one-out method. RESULTS: The analysis included 87 single nucleotide polymorphisms (SNPs) associated with AF. The results from the IVW method indicated a positive association between genetic predisposition to AF and the risk of stroke (OR 1.002, 95 % CI 1.001-1.003, P < 0.001). The weighted median and MR-Egger methods showed consistent results (weighted median: OR 1.001, 95 % CI 1.000-1.002, P = 0.034; MR-Egger: OR 1.001, 95 % CI 1.000-1.003, P = 0.086). Sensitivity analysis demonstrated that no individual SNP significantly influenced the causal inference. CONCLUSIONS: This study provides evidence of a causal relationship between AF and an elevated risk of stroke. These findings emphasize the significance of managing AF in order to prevent and treat strokes. Additional research is required to better understand the underlying mechanisms of this causal association.

Danshao Shugan Granule therapy for non-alcoholic fatty liver disease.

BACKGROUND: Danshao Shugan Granules (DSSG), a traditional Chinese medicine (TCM), is given to protect the liver. The objective is to evaluate the mechanisms of the effects of DSSG on non-alcoholic fatty liver disease (NAFLD). METHODS: 260 patients with NAFLD were randomly allocated to positive control drugs rosiglitazone (n = 30) and Silibinin (n = 50) as well as DSSG (n = 130) and combined DSSG/Silibinin (n = 50) groups, from which 90 patients in the DSSG group were further subdivided into 3 groups (n = 30, each) depending on the severity of symptoms. In total 33 Sprague-Dawley rats were assigned to normal (n = 10) or 45% high-fat diet (n = 23) groups, from which 9 rats served as negative controls, 10 as model controls and 10 were treated with DSSG. RESULTS: DSSG medications had significantly highest effects on B-ultrasonography finding improvements, and reductions of total cholesterol, triglyceride, aspartate transaminase and γ-glutamyl transpeptidase in NAFLD patients. Silibinin application only led to significantly highest alanine transaminase reductions and rosiglitazone medication to significantly highest fasting plasma glucose reductions. In a murine in vivo NAFLD model glucose (GLU), total cholesterol (TC) triacylglycerol (TG) as well as glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and gamma-glutamyl transferase (GGT) serum concentrations were all significantly reduced (P < 0.001) and the expression of nuclear factor-κB (NF­κB) was significantly decreased in DSSG treated compared to untreated NAFLD animals (P < 0.001). In addition, the DSSG treated rats exhibited increased superoxide dismutase activity and reduced malondialdehyde values. CONCLUSIONS: DSSG was effective for treating NAFLD patients, which could be attributed to increased activity of superoxide dismutase, a decrease of malondialdehyde as well as reduced NF­κB activity in a NAFLD rat model.

CircHOMER1 aggravates oxidative stress, inflammation and extracellular matrix deposition in high glucose-induced human mesangial cells.

BACKGROUND: Circular RNAs (circRNAs) play an important regulatory role in human diseases, including diabetic nephropathy (DN). The purpose of this study was to investigate the role and mechanism of circHOMER1 action in DN. METHODS: Human mesangial cells (HMCs) were tested with high glucose (HG) to mimic DN cell models. Quantitative real-time PCR was performed to determine circHOMER1, microRNA (miR)-137 and SRY-box transcription factor 6 (SOX6) expression. SOD activity and MDA level were detected to evaluate cell oxidative stress. ELISA assay was used to analyse the levels of inflammation factors. The protein levels of extracellular matrix (ECM) deposition-related markers and SOX6 were assessed by western blot analysis. The interaction between miR-137 and circHOMER1 or SOX6 was analysed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: CircHOMER1 was highly expressed in HG-induced HMCs and DN patients. Downregulation of circHOMER1 suppressed oxidative stress, inflammation and ECM deposition in HMCs induced by HG. In terms of mechanism, circHOMER1 could sponge miR-137 to regulate SOX6. Function assays showed that miR-137 inhibitor or SOX6 overexpression revoked the negative regulation of circHOMER1 knockdown on HG-induced HMCs injury. In addition, miR-137 expression was negatively correlated with circHOMER1 and SOX6 expression in DN patients. CONCLUSION: CircHOMER1 promoted HG-induced HMCs oxidative stress, inflammation and ECM accumulation via the miR-137/SOX6 axis, suggesting that circHOMER1 might be a target for DN treatment.

Liuwei Dihuang Pill Attenuates Diabetic Nephropathy by Inhibiting Renal Fibrosis via TGF-ß/Smad2/3 Pathway.

Among all the complications of diabetes, diabetic nephropathy is a significant factor causing the end-stage renal disease associated with high death rates. Current treatment fails to produce an ideal outcome. Thus, searching for a new preventive drug is urgently needed. Liuwei Dihuang pill (LDP), a popular ancient Chinese medicine (TCM) prescription, has been applied to treat DN-like syndromes according to TCM theory. Here, we had established an animal model with DN and LDP therapy was put into use to assess its therapeutic effect in vivo. Our data showed that oxidative stress and TGF-ß/Smad2/3 pathway-induced renal fibrosis could be observed in the DN animal model. However, the treatment of LDP impeded the generation of ROS and attenuated renal fibrosis-related proteins in damaged kidneys through interference in the TGF-ß/Smad3 pathway. Our results indicated that LDP attenuated oxidative stress, accompanied by preventing the production of renal fibrosis through inhibiting the TGF-ß/Smad2/3 pathway.

Efficacy and Safety of Ejiao (Asini Corii Colla) in Women With Blood Deficient Symptoms: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

Equus asinus L [Equidae; Asini Corii Colla] (donkey-hide gelatin, Ejiao), a well-known traditional Chinese medicine, has been widely used to nourish the blood, especially for women. The aim of this study was to assess the efficacy and safety of Ejiao in blood-deficient patients. A total of 210 participants were recruited and randomly allocated into the placebo control group and Ejiao-treated group (6 g/day). The primary outcomes on the efficacy of Ejiao included traditional Chinese medicine symptom scores, blood indicators, and SF-36. The secondary outcomes were changes in fireness and safety evaluation. Results showed that Ejiao treatment for 8 weeks had significantly improved dizziness symptoms. Among the tested 24 blood biochemical parameters, the hematocrit and red blood cell numbers decreased in the placebo control group, but decreased significantly less in the Ejiao treatment group. The white blood cell and neutrophil counts increased in the Ejiao group but were within the normal range. In addition, the quality of life improved as the scores in SF-36 domains were significantly higher in the Ejiao group. At the same time, there was no significant change in the fire-heat symptoms score or other safety parameters. Considering all these, our study showed that Ejiao has a promising effect in women suffering from blood deficiency without obvious adverse effects.

Effects of Shaoyao-Gancao Decoction on Infarcted Cerebral Cortical Neurons: Suppression of the Inflammatory Response following Cerebral Ischemia-Reperfusion in a Rat Model.

The mechanisms by which Shaoyao-Gancao decoction (SGD) inhibits the production of inflammatory cytokines in serum and brain tissue after cerebral ischemia-reperfusion (CI-RP) in rats were investigated. A right middle cerebral artery occlusion was used to induce CI-RP after which the rats were divided into model (n = 39), SGD (n = 28), clopidogrel (n = 25) and sham operated (n = 34) groups. The Bederson scale was used to evaluate changes in behavioral indices. The levels of IL-1ß, TNF-α, MCP-1, IL-10, RANTES, VEGF, and TGF-ß1 in the serum and infarcted brain tissues were measured. Nissl body and immunohistochemical staining methods were used to detect biochemical changes in neurons, microglial cells, and astrocytes. Serum levels of VEGF, TNF-α, MCP-1, IL-1ß, and IL-10 increased significantly 24 h after CI-RP. In brain tissue, levels of TNF-α and IL-1ß significantly increased 24 h after CI-RP, whereas levels of TGF-ß1 and MCP-1 were significantly higher 96 h after CI-RP (P < 0.05). SGD or clopidogrel after CI-RP reduced TNF-α and IL-1ß levels in brain tissue and serum levels of MCP-1, IL-1ß, and IL-10. SGD increased the number of NeuN-positive cells in infarcted brain tissue and reduced the number of IBA1-positive and GFAP-positive cells. The efficacy of SGD was significantly higher than that of clopidogrel.