Research of the mechanism of Huganning tablet in the treatment of nonalcoholic fatty liver disease based on network pharmacology and computer-aided drug design / 药学学报

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Nutritional status and metabolic syndrome risk according to the dietary pattern of adult single-person household, based on the Korea National Health and Nutrition Examination Survey / 한국영양학회지

Purpose@#This study was undertaken to evaluate the health, nutritional status and metabolic syndrome risk according to the dietary pattern of adult single-person households, using information obtained from the Korea National Health and Nutrition Examination Survey (KNHANES). @*Methods@#Data were collected from the 2013–2016 KNHANES, of adults aged 19–64 years, belonging to single-person households. Based on cluster analysis, the dietary patterns of subjects were classified into three groups. The dietary behavior factors, health-related factors, nutritional status, and prevalence of metabolic syndrome obtained from KNHANES questionnaires were compared according to the individual dietary pattern. The nutrient intake data of the subjects were calculated using the semi-food frequency questionnaire.Moreover, blood and physical measurement data of the subjects were analyzed to obtain the prevalence of metabolic syndromes. @*Results@#The major dietary intakes of subjects were classified as ‘Rice and kimchi’, ‘Mixed’, and ‘Milk·dairy products and fruits’ patterns. Characteristics of subjects based on their dietary pattern, gender, age, and education level were significantly different. The ‘Milk and fruits’ pattern showed low frequency of skipping breakfast and eating out, and had higher intake of dietary supplements. Frequency of alcohol intake and smoking rates were highest in the ‘Mixed’ pattern. Maximum nutrient intake of fat, vitamin A, riboflavin, vitamin C, niacin, calcium, phosphorus, and potassium was obtained in the ‘Milk·dairy products and fruits’ pattern. According to dietary patterns adjusted for age and gender, the risk of metabolic syndrome was 0.380 times lower in the ‘Milk·dairy products and fruit’ pattern than in the ‘Rice and kimchi’ pattern. However, when adjusted for other confounding factors, no significant difference was obtained between dietary patterns for metabolic syndrome risk. @*Conclusion@#These results indicate that the health and nutritional status of a single-person household is possibly affected by the dietary intake of subjects.

Vitamin A supplementation modifies the antioxidant system in rats

BACKGROUND/OBJECTIVES: It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats. MATERIALS/METHODS: Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope. RESULTS: Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation. CONCLUSIONS: These results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.

Methylation status of CDH1 gene in preoperative abdominal lavage of patients with gastric cancer and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the association between the progression of gastric cancer and the aberrant methylation of CDH1 gene in preoperative abdominal lavage fluid.</p><p><b>METHODS</b>Real-time methylation-specific polymerase chain reaction(qMSP) was used to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands from preoperative abdominal lavage fluid in 92 patients with gastric cancer. The associations between methylation of CDH1 genes and clinicopathologic features and prognosis were investigated.</p><p><b>RESULTS</b>Among the 92 patients with gastric cancer, aberrant methylation of CDH1 gene was detected in 45(48.9%) patients, including total aberrant methylation in 12(13.0%) cases and partly aberrant methylation in 33(35.9%) cases. Significant associations were found between CDH1 methylation status and tumor size, growth pattern, differentiation, lymphovascular invasion, infiltration depth, lymph node metastasis, distant metastasis, and clinical staging(all P<0.05). However, there were no significant associations between CDH1 methylation status with gender, age, tumor location, or Helicobacter pylori infection(all P>0.05). The median progression-free survival was 20 months for CDH1 methylation group and 38 months for non-methylated group, and the difference was statistically significant(P<0.01). Cox model analysis revealed that CDH1 methylation status in preoperative peritoneal lavage fluid was an independent factor associated with postoperative survival in patients with gastric cancer(P=0.000, RR=332.88, 95%CI:21.71-5105.07).</p><p><b>CONCLUSIONS</b>The aberrant methylation of 5'-CpG of CDH1 gene promoter is common in gastric cancer. The examination of CDH1 methylation status of abdominal lavage should be considered in the progression of gastric cancer.</p>

Impact of lymphocytes subgroups in peripheral blood on survival rate of patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the change of lymphocyte subgroups in the peripheral blood of patients with gastric carcinoma and its association with survival.</p><p><b>METHODS</b>Flow cytometry was used to examine the subgroups of lymphocytes (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD19(+), CD25(+), CD44(+) and NK cells) in the peripheral blood of 833 gastric carcinoma patients prior to any therapy. Patients were divided into the high expression group and lower expression group according to the average test values of 96 healthy control subjects. Survival rate was compared between the two groups.</p><p><b>RESULTS</b>Compared with control group, the levels of CD3(+) and CD8(+) T cell in patients were significantly lower, while the levels of CD4(+), CD19(+), CD25(+), CD4(+)/CD8(+), CD44(+), and NK(+) cells were significantly. The differences were statistically significant(P<0.05). Three-year survival rates of gastric cancer patients with high CD19(+) expression (n=444) and cases with low CD19(+) expression (n=389) were 36.4% and 18.5%, respectively(P<0.05). The expressions of other seven types of lymphocytes were not associated with survival rates (all P>0.05).</p><p><b>CONCLUSIONS</b>Significant changes in lymphocyte subgroups exist in the peripheral blood of patients with gastric carcinoma. Patients with high CD19(+) expression have better survival.</p>