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ObjectiveTo observe the effect of Shenling Baizhusan on the intervention of the nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway by regulating ferroptosis in rats with alcoholic liver injury. MethodForty SD rats were randomly divided into model group， polyene phosphatidylcholine group， and high， medium， and low-dose Shenling Baizhusan groups， with 8 rats in each group. Another 8 SD rats were taken as blank group. The model group， polyene phosphatidylcholine group， high， medium， and low-dose Shenling Baizhusan groups were given 10 mL·kg-1 liquor by gavage for modeling， and the blank group was given equal volume of distilled water by gavage. After 4 h of daily alcoholic administration， 143.64 mg·kg-1 of polyene phosphatidylcholine group was given to the polyene phosphatidylcholine group， 15， 7.5， 3.75 mg·kg-1 of Shenling Baizhusan were given to Shenling Baizhusan high， medium， and low-dose groups， respectively， and the blank group and the model group were given equal volume of distilled water. The gavage lasted for 6 weeks. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， glutamyl transpeptidase （GGT）， total cholesterol （TC）， and triglyceride （TG） were detected by automatic biochemical analyzer. The levels of tumor necrosis factor-α （TNF-α） and interleukin-β （IL-β） were detected by the enzyme-linked immunosorbent assay （ELISA）. The levels of lipopolysaccharide （LPS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）， and Fe+ were detected by biochemical assay. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The mRNA expression levels of Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， ferritin heavy polypeptide 1 （FTH1）， and nuclear factor-κB （NF-κB） were detected by Real-time polymerase chain reaction （Real-time PCR）. The protein expression levels of Nrf2， HO-1， GPX4， FTH1， p65， and phosphorylation （p）-p65 were detected by Western blot. ResultAs compared with the blank group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the model group were significantly increased （P<0.05）. The liver showed obvious steatosis， with a large number of fat deposition， the oxidative stress and inflammatory factors were significantly increased （P<0.05）， and the level of Fe+ was significantly increased in model group （P<0.05）. The protein expression levels of Nrf2， HO-1， GPX4， and FTH1 was significantly down-regulated （P<0.05）， and those of p65 and p-p65 was significantly up-regulated in the model group （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly down-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly up-regulated （P<0.05）. As compared with the model group， the levels of liver function （ALT， AST， and GGT） and blood lipids （TC and TG） in the high-dose and medium-dose Shenling Baizhusan groups were significantly decreased （P<0.05）， liver steatosis was significantly improved， fat deposition was significantly reduced， oxidative stress and inflammatory factors were significantly decreased （P<0.05 ）， and Fe+ level was significantly decreased （P<0.05）. In the high-dose and medium-dose Shenling Baizhusan， the protein expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and those of p65， p-p65 were significantly down-regulated （P<0.05）. The mRNA expression levels of Nrf2， HO-1， GPX4， and FTH1 were significantly up-regulated （P<0.05）， and the mRNA expression level of NF-κB was significantly down-regulated （P<0.05）. ConclusionShenling Baizhusan can effectively reduce liver injury in rats with ALD， regulate steatosis and fat deposition， and play an antioxidant and anti-inflammatory role in the liver. Its mechanism may be related to the inhibition of ferroptosis in hepatocytes by up-regulating the Nrf2 signaling pathway to improve oxidative stress
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Objective:To investigate the expression and the significance of inflammatory cytokine IL-6 through regulating Gli1 in acute pancreatitis.Methods: In this study,C57 mice were randomly divided into three groups:control group,model group,inhibitor group.caerulein intraperitoneal injection induce acute pancreatitis model.Use HE staining and amylase to testify the model successfully.Use RT-qPCR,Western blot to detect the expression of Gli1 in the pancreas,liver,lung,kidney and intestine and ELISA method to detect inflammatory cytokines IL-6.Results: Compared with control group,the expression of Gli1 is higher in model group,then the expression of IL-6 increases in inhibitor group which uses Gant61 to suppress Gli1 compared with model group.Conclusion: Gli1 may involved in the process of the distant tissue injury and repair in acute pancreatitis and through regulate its downstream cytokines like IL-6 to play a protective role in acute pancreatitis.
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Objective The aim to assess the methodology and feasibility of ultrasound guided percutaneous thrombin injection(UGTI) for the treatment of Iarogenic Femoral Arterial Complexity Pseudoaneurysms(IFACP).Methods Thirty two iarogenic femoral arterial complexity pseudoaneurysms patients following femoral arerial puncture for arterial angiography were treated with UGTI.Twenty-three IFACP with 2 lobes,8 IFACP with 3 lobes,1 IFACP with 4 lobes.Under local anesthesia the lobe was pene trated by artery needle successively and thrombin jection was performed slowely into distal lobe with US guide precise localization.Dynamical observation was performed for the status of thrombogenesis and cavity plugging.US follow-up examination were performed after 24 h and 7 d.Results Reperfusion occurred in IFACP with 3 lobes after 24 h and UGTI failure.IFACPs with 4 lobes failure.Nothromboembolic,infectious,allergic complication soccurred.Conclusion UGTI is the first mothed for the treatment of IFACP.Precise localization and percutaneous can enhance the ratio of treatment of IFACPs and avoid the severe complications.
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Objective To detect the genome-wide profiles of DNA methylation in human hepatocellular carcinoma (HCC) cells and to identify the distribution of differentially methylated sites and genes in order to explore the relationship between aberrant DNA methylation and hepatocellular carcinoma.Methods The Infinium Human Methylation 450K BeadChip was used to identify the genome-wide aberrant DNA methylation profiles in Huh7 and L02 cell lines.Results Totally 102 254 differentially methylated CpG sites and 26 511 genes,involving 43 signaling pathways,were detected when Huh7 and L02 cell lines were compared.The absolute β-difference in 57.3％ of the hypermethylated CpG sites and 39.4％ of the hypomethylated CpG sites was reported to be ≥ 50％.A total of 3 222 hypermethylated genes and 2 204 hypomethylated genes were identified.Conclusion We detected many aberrant methylated sites and genes in HCC cells.The abnormal DNA methylation exhibits an important role in the occurrence and development of HCC.
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Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients’ peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.
Subject(s)
Humans , Apoptosis , Blood Cells , Blotting, Western , Cell Proliferation , Drug Resistance , Imatinib Mesylate , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Luciferases , Phenotype , RNA , RNA, Long NoncodingABSTRACT
Objective To investigate the role of apoptosis and the regulating role of receptor interacting protein 1(RIP1) in acute pancreatitis .Methods Thirty C57 mice were divided into three groups :control group ,acute edematous pancreatitis (AEP) group and acute necrotizing pancreatitis (ANP) group .The AEP group was continuously injected by cerulein 50 μg/kg for 13 times ,the ANP group was continuously injected by cerulein 50μg/kg for 13 times and lipopolysaccharide 15 mg/kg once;the con‐trol group was injected by the same volume of normal saline for 7 times .The acinar cell apoptosis was observed by the terminal de‐oxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling (TUNEL) assay .The RIP1 mRNA expression was measured by real time fluorescence PCR .The expression of RIP1 protein was detected by Western blotting .Results The mouse models of AEP and ANP were established successfully .Compared with the control group ,acinar cell apoptosis existed in both AEP and ANP model groups ,moreover compared with the AEP group ,apoptosis in the ANP group were decreased ,the differences were statistically significant(P<0 .05) .Compared with the control group ,the expression of RIP1 mRNA and protein in the AEP group was increased ,while which in the ANP group were decreased ,the differences were statistically significant(P<0 .05) .Conclusion RIP1 participate in the pathogenesis of acute pancreatitis ,which may associate with acinar cell apoptosis .
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Objective To establish a simple method to extract the methylated ctDNA in urine using magnetic beads as solid phase adsorption carri?er with a specific design reagent system and extraction process,and evaluate its application feasibility for methylated gene detection in urine sample . Methods Fourty cases of methylated ctDNA were extracted in urine using magnetic beads. After methylated modification,the concentration and pu?rity of DNA was determined by ultraviolet spectrophotometer. Results The extraction of 50 mL urine can gain 61?200 ng/mL methylated ctDNA, and the OD260/280 was 1.8 ± 0.05. Conclusion There are methylated ctDNA exist in the urine which can be extracted by magnetic beads. The estab?lished extraction method is simple,effective,and with high purity.
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Objective To explore the suitable range of PT-INR for Chinese people with acute deep venous thrombosis (DVT) treated by warfarin anticoagulation therapy. Methods Eighty seven DVT patients with indications to warfarin anticoagulation therapy were enrolled into the study and divide into two groups randomly. Patients from group A (n=47) took warfarin to adjust the PT-INR to range 1.7-2. 5,and patients from group B (n =40) took warfarin to adjust the PT-INR to range 2. 0-3. 0. The therapeutic effectiveness and the incidence of bleeding complications were compared between two groups. Results Forty-six patients (46/47,98%) had limb swelling symptoms relief in group A with one exception,which was diagnosed as pelvic tumor by ultrasonography,CT and tumor markers examination later. No patient underwent bleeding in group A Thirty eight patients (38/40,93%) had limb swelling symptoms relief in group group B with two exceptions,of which one case had Cockett syndrome and the other one had unknown aetiology. The total effective rate of group B was 95% . As to the complications of this group,3 patients had slight gum and nasal mucous membrane bleeding, 1 patient developed gastrointestinal bleeding. No patients had pulmonary embolism in both groups. Conclusion For Chinese people,anticoagulation therapy of acute deep venous thrombosis to adjust the range of PT-INR to 1.7-2. 5, shows good effectiveness and significantly reduced bleeding complications.
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Objective To investigate the role of Wnt/β-catenin signaling pathway in impaired wound healing of diabetes mellitus.Methods The back skin defect was produced in rats with type1diabetes.All of these rats were divided into normal group, diabetes group, lithium chloride group, and epidermal growth factor (EGF) group.The back wound healing and β-catenin expression were observed.Results There were no signs of infection in the wound of rats after injury.Compared with diabetic group, the wound healing time was shorter,wound healing rate was higher, wound cavity volume was smaller, granulation tissue was more mature, and β-catenin positive cell rate was higher in normal group, lithium chloride group, and EGF group(P＜0.05 or P＜0.01).Conclusions Wnt/beta-catenin signaling pathway is involved in the process of wound healing in diabetic rats.
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Diabetic vascular disease is a major complication of diabetes, which is characterized by the formation of collateral vessels of serious damage to systemic disease. Substantial evidence have shown that timpaired endothelial progenitor cell function, non-enzymatic glycation end products accumulate, and Wnt signaling pathway dysfunction may be an important mechanism of impaired angiogenesis after the diabeticlimb ischemic. This paper is to make a study of its mechanism, and to provides a new strategy for diabetes therapeutic angiogenesis.
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To study the significance of the levels of plasma inflammatory cytokines (IL-6,IL-8,IL-10 and TNF-?) in patients with acute deep venous thrombosis (DVT) of lower extremity. Methods Forty untreated DVT cases were selected as the subjects in the DVT group, while thirty healthy subjects, whose ages and genders showed no significant difference with the DVT patients, were collected as the control group. The plasma levels of IL-6, IL-8 and TNF-? were detected by radioimmunoassay (RIA), and the plasma level of IL-10 was measured by enzyme-linked immunosorbent assay (ELISA). Correlation analysis was used to investigate the relationships between the levels of different inflammatory cytokines within DVT group. Results The levels of plasma cytokines in the DVT group were all significantly higher than those in control group (P