摘要
Objective @#To investigate the changes of lipid biomarkers and lipid metabolic pathways related to liver injury in BTBR ob/ob mice with type 2 diabetes mellitus by biochemical and metabolomics methods.@*Methods @# 16 BTBR wild-type (WT) mice (WT group) and 14 BTBR ob/ob obese mice (ob / ob group) at 7 weeks of age were selected and fed in SPF environment until 20 weeks of age.Liver injury was compared between the two groups : The activities of mitochondrial respiratory enzyme complex in liver tissue were detected by high-resolution respirators,and the lipid metabolomic analysis of liver tissue samples in the two groups of mice was performed by ultra-perform- ance liquid chromatography-quadrupole time-of-flight mass spectrometry,mainly detecting endogenous metabolites. Principal component analysis (PCA) ,orthogonal partial least squares discriminant analysis ( OPLS-DA) and other models were used to screen potential biomarkers,and the metabolic pathway analysis of the identified metabolites was performed by MetaboAnalyst 5. 0 . @*Results @#Compared with the WT group,the ob / ob group had significantly increased body weight,fasting blood glucose ,serum levels of aspartate aminotransferase ( AST) ,alanine amin- otransferase (ALT) ,low-density lipoprotein (LDL-C) and cholesterol ( CHO) (P<0. 01) .Liver hematoxylin-eo- sin staining (HE) staining showed that the mice in ob / ob group had structural disorder of liver lobules,swelling of liver cells ,a large number of fat vacuoles in cells ,diffuse distribution and loose cytoplasm. Oil red O staining showed that there was a large amount of lipid deposition in the hepatocytes ofob/ob mice.The high resolution spi- rometer showed that the ob/ob mice had mitochondrial oxidative phosphorylation disorder and the activity of complex Ⅳ decreased.Lipid metabolomic analysis showed that the lipid metabolic profile of ob/ob mice changed,and the metabolic pathways involved mainly included glycerophospholipid metabolism,glycosylphosphatidylinositol ( GPI) anchor biosynthesis,triglyceride metabolism,linoleic acid metabolism,α-linolenic acid metabolism and arachidon- ic acid metabolism.@*Conclusion @#The liver injury of ob / ob group mice may be related to the disorder of lipid me- tabolism,in which the disorder of glycerophospholipid metabolism is the most critical metabolic pathway.
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AIM: To investigate the mechanism and reversal effect of Zuo Jin Wan (ZJW) on cetuximab (CET) resistance in KRAS mutant colorectal cancer cell. METHODS: The mutation status of KRAS gene in SW620, Lovo, HCT116, HT29 and Caco2 cells were detected by Sanger sequencing. CCK-8 assay was used to detect the effects of ZJW, CET, ZJW combined with CET and CET, ZJW in combination with other cell death inhibitors on the survival rate of the above cells, and to observe the reversal effects of ZJW on CET-treated KRAS mutant cells (SW620, Lovo and HCT116). Flow cytometry, colorimetric method, and Fe
摘要
Objective To investigate related influencing factors in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods A total of 252 patients with T2DM who were treated in Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine from May 2021 to March 2022 were enrolled as subjects, and these patients were also included in Metabolic Management Center of China. According to the presence or absence of fatty liver disease, the patients were divided into simple T2DM group ( n =105) and T2DM+NAFLD group ( n =147). Related general data were analyzed, including sex, age, blood pressure, body height, body weight, neck circumference, triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, fasting blood glucose, glycosylated hemoglobin, high-sensitivity C-reactive protein, albumin/creatinine ratio in morning urine, thyroid stimulating hormone, uric acid, intrahepatic fat deposition, carotid intima-media thickness, and brachial-ankle pulse wave velocity. The group t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was used to investigate the risk factors for T2DM with NAFLD, and the receiver operating characteristic (ROC) curve was used to assess the predictive value of related influencing factors. Results The age-stratified analysis showed that in the < 50 years age group, compared with the patients with T2DM alone, the patients with T2DM and NAFLD had significantly higher levels of body mass index (BMI), visceral fat, TG, brachial-ankle pulse wave velocity, albumin/creatinine ratio in morning urine, and uric acid ( P < 0.05); in the ≥50 years age group, compared with the patients with T2DM alone, the patients with T2DM and NAFLD had significantly higher levels of blood pressure, BMI, visceral fat, TG, brachial-ankle pulse wave velocity, albumin/creatinine ratio in morning urine, and uric acid ( P < 0.05) and a significantly lower level of serum HDL-C ( P < 0.05). The multivariate logistic regression analysis showed that BMI (odds ratio [ OR ]=1.408, 95% confidence interval [ CI ]: 1.136-1.746, P =0.002), HDL-C ( OR =0.031, 95% CI : 0.001-0.647, P =0.025), left brachial-ankle pulse wave velocity ( OR =1.003, 95% CI : 1.001-1.006, P =0.003), and uric acid ( OR =1.011, 95% CI : 1.005-1.016, P < 0.001) were independent influencing factors for T2DM with NAFLD. The ROC curve analysis showed that HDL-C, BMI, left brachial-ankle pulse wave velocity, and uric acid had an area under the ROC curve of 0.695 (95% CI : 0.574-0.812), 0.708 (95% CI : 0.628-0.788), 0.611 (95% CI : 0.523-0.698), and 0.698 (95% CI : 0.617-0.779), respectively, in evaluating T2DM with NAFLD. Conclusion Low levels of HDL-C, BMI, left brachial-ankle pulse wave velocity, and uric acid have a certain value in predicting NAFLD in patients with T2DM.
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Nonalcoholic fatty liver disease (NAFLD) has become the most important chronic liver disease and is recognized as the hepatic manifestation of metabolic syndrome, which may progress to liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma in the advanced stage. Gut microbiota, as important symbiotic organisms in the human body, affects metabolic function and may be closely associated with NAFLD, and the theory of gut-liver axis provides a theoretical basis for understanding that intestinal dysbacteriosis may cause liver pathological changes. This article explores the association between NAFLD and gut microbiota, so as to lay a theoretical foundation for the future research on the therapy for NAFLD targeting gut microbiota.
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Hepatorenal syndrome (HRS) is a common complication of severe liver disease, with severe conditions and poor prognosis, and causes a great burden to both patients’ family and society. HRS has a complex pathogenesis, and Western medicine treatment has a limited therapeutic effect; therefore, integrated traditional Chinese and Western medicine therapy is a feasible treatment method with a good clinical effect. This article reviews the advances in the diagnosis and treatment of HRS in both modern and traditional medicine, so as to overcome this challenge as early as possible.
摘要
Nonalcoholic fatty liver disease (NAFLD)is a clinicopathological syndrome characterized by diffuse macrovesicular steatosis in hepatocytes and is caused by the factors except excessive drinking and other specific factors for liver injury. In particular,lipid metabolism disorder is a significant characteristic of NAFLD,and improvement of dyslipidemia is an important method for the prevention and treatment of NAFLD. Lipid - regulating drugs can not only reduce blood lipids,but also promote the transportation of lipids to the liver for metabolism, which may cause liver lipid accumulation and aggravate liver injury. At present,there are still controversies over the application of lipid -regulating drugs in the treatment of NAFLD in China. Rational use of lipid - regulating drugs has become an important topic in the prevention and treatment of NAFLD. This article summarizes the application of lipid - regulating drugs in NAFLD,in order to provide a reference for lipid - regulating drugs in the prevention and treatment of NAFLD.
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Objective: To study the protective effect of vitamin E in preventing contrast-induced nephropathy (CIN) in patient with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Methods: We prospectively studied 206 CAD patients with elective PCI in our hospital and divided them in 2 groups: Treatment group, the patients received oral vitamin E combining vinous hydration,n=102 and Control group, the patients received vinous hydration only,n=104. CIN was deifned by at 48h after contrast media injection, serum cretinin increased up to 25% from the baseline, or reached 44.2 μmol/L. Excluding the other kidney injury factors, the renal functions at 48 h before and after PCI were compared, the occurrence rate of CIN were also compared between 2 groups. Results:①Overall, there were 19/206 (9.22%) patients suffered from CIN, the occurrence rate in Treatment group (4.90%) was lower than Control group (13.46%), χ2=4.506,P=0.034. For patients with hypertension, diabetes, chronic kidney disease, anemia and mehran risk score10 (OR= 4.461, 95% CI 1.589-14.724) were the independent risk factors for CIN occurrence, allP Conclusion: Short-term application of vitamin E may reduce the risk of CIN occurrence at certain degree in CAD patients after PCI.
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BACKGROUND:It has been found that cel ular repressor of E1A-stimulated genes (CREG) is a lysosomal protein binding directly to the mannose-6-phosphate (M6P)/insulin-like growth factor II receptor (IGFIIR) and depends on the interaction with M6P receptors for efficient delivery to lysosomes OBJECTIVE:To study the interactions between the exogenous CREG protein and cathepsins and M6P/IGFIIR and to confirm the effect of CREG protein on expression and distribution of M6P/IGFIIR. METHODS:Double-stained immunofluorescence and coimmunoprecipitation were applied to observe the interactions between the exogenous CREG protein and cathepsin B, cathepsin L and M6P/IGFIIR. Using gain-of-function and loss-of-function approaches, the effect of CREG on expression and distribution of M6P/IGFIIR were studied by western blot assay and immunofluorescence staining. RESULTS AND CONCLUSION:Double-stained immunofluorescence and coimmunoprecipitation analyses confirmed the direct interactions between the exogenous CREG protein and cathepsin B, cathepsin L and M6P/IGFIIR. It was verified that CREG plays a critical role not in the expression but in the distribution of M6P/IGFIIR using gain-of-function and loss-of-function approaches. These findings provide evidence that exogenous CREG protein is located in lysosomes and has interactions with cathepsins and M6P/IGFIIR, also CREG plays a critical role in the distribution of M6P/IGFIIR.
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To investigate the effects of three classical anti-jaundice formulas Yinchenhao Decoction (YCHD). Yinchen Wuling San (YCWLS) and Zhizi Baipi Decoction (ZZBPD) on liver fibrosis induced by dimethylnitrosamine (DMN) in rats and explore the formula-syndrome relationship.
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This study is to establish a method for simultaneously determination of five nucleosides and nucleobases, including hypoxanthine, uridine, adenine, guanosine and adenosine in Rehmannia glutinosa Libosch. which was collected from different regions in China. A Diamonsil C18 column (250 mm x 4.6 mm, 5 microm) was used. Acetonitrile and 0.04 mol L(-1) potassium dihydrogen phosphate solution were adopted as mobile phase with gradient elution. The flow rate was 1 mL min(-1) and column temperature was 30 degrees C. The detection wavelength was at 254 nm. The method had good linearity over the range of 1.0 - 16.0 microg mL(-1) (r2 = 0.999 8), 5.0 - 80.0 microg mL(-1) (r2 = 0.999 8), 1.0 - 16.0 microg mL(-1) (r2 = 0.999 5), 1.25 - 20.0 microg mL(-1) (r2 = 0.999 8) and 1.0 - 16.0 microg mL(-1) (r2 = 0.999 8) for hypoxanthine, uridine, adenine, guanosine and adenosine, respectively. The average recoveries were between 98.8% and 100.7%. The content of hypoxanthine, uridine, adenine, guanosine and adenosine in Rehmannia glutinosa Libosch. from different regions was significantly different. This established method was sensitive and reliable for the quantification of five chemical constituents in Rehmannia glutinosa Libosch.
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To evaluate the effects of Xiayuxue Decoction, a compound traditional Chinese medicine, on liver angiogenesis in rats with carbon tetrachloride (CCl(4))-induced liver fibrosis.
摘要
Objective: To investigate the different efficacy of Yinchenhao Decoction (YCHD), a compound traditional Chinese herbal medicine, for liver cirrhosis induced by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl(4)) in rats. Methods: To induce liver fibrosis, 0.5% DMN solution (2mL/kg body weight, i.p.) was given three consecutive days a week to male Wistar rats for 4 weeks. Cirrhotic rats were randomly divided into DMN group, YCHD group, Xiaochaihu decoction group by the end of the fourth week to accomplish a 2-week recipe treatment course. In CCl(4)-induced liver fibrosis model, 50% CCl(4)-olive solution was injected subcutaneously to rats at a dose of 2 mL/kg body weight twice a week to duplicate rat cirrhosis model. After 8 weeks, rats were divided into CCl(4) group, CCl(4) plus YCHD group and Xiaochaihu decoction group. For the YCHD group, YCHD was administered intragastrically once a day for 4 weeks. For DMN or CCl(4) model, by the end of 6 or 12 weeks respectively, rats were sacrificed for sampling to detect liver function, hepatic histological changes, hydroxyproline (Hyp) content and apoptosis-related gene expressions. Results: In DMN liver fibrosis model, hepatic fibrosis was obvious at week 2 and cirrhosis was evident at week 4 in DMN-treated rats. Compared to 6-week DMN group, hepatic pathological changes and liver function were improved significantly and content of Hyp decreased remarkably in YCHD group. In CCl(4)-induced liver fibrosis model, hepatic fibrosis was obvious at 8 weeks and cirrhosis was evident at 12 weeks in CCl(4)-treated rats. Compared to 12-week CCl(4) group, hepatic pathological changes and liver function were not obviously improvement in YCHD group. The results of gene chip showed that YCHD significantly decreased Fas, Bax and caspase-3 gene expressions, and increased Bcl-xL gene expression in the liver of DMN model. However, in the model induced by CCl(4), YCHD did not inhibit hepatocyte apoptosis induced by CCl(4), but increased tyrosine kinase receptor gene expression by 4.8 times. Conclusion: YCHD exerts more significant therapeutic effects on DMN-induced than CCl(4)-induced cirrhosis in rats in Hyp content and pathological change in liver tissue.
摘要
OBJECTIVE: To explore the antitumor activities of kushen (Sophora flavescens) flavonoids (KS-Fs) in vivo and in vitro. METHODS: Cell proliferation was assayed by using methyl thiazolyl tetrazolium (MTT) method. H22 hepatocellular carcinoma and S180 sarcoma were induced in ICR mice. Lewis lung carcinoma was induced in C57BL/6 mice. H460 and Eca-109 tumor were induced in Balb/c nude mice by injecting 5x10(5) or 5x10(6) tumor cells in the right flank, respectively. RESULTS: KS-Fs could inhibit the growth of a variety of human tumor cell lines (A549, SPC-A-1, NCI-H460, etc.) in vitro. The antitumor efficacies were confirmed in the mice models of H22, S180 and Lewis lung tumors and the nude mice models of human H460 and Eca-109 xenografted tumors. The oral or intravenous maximum tolerated dose of KS-Fs was more than 2.8 g/kg or 750 mg/kg respectively, far more than the oral medial lethal dose of kushen alkaloids (< or = 1.18 g/kg). No adverse reactions were observed. CONCLUSION: These results suggest that KS-Fs or kurarinone may be developed as a novel antitumor agent.