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Hepatitis B virus （HBV） is considered a “metabolic virus” that can influence a variety of metabolic processes. There is still a lack of definite conclusion on the association between chronic HBV infection and the various types of metabolic dysfunction， and little is known about the mechanism of the association of chronic HBV infection with the diseases characterized by metabolic disorder， such as metabolic syndrome， diabetes， and metabolic associated fatty liver disease. Currently it is believed that hepatitis B x gene （HBx）， derived from HBV genome， might play an important role in mediating systemic metabolic alterations after HBV infection， and HBx influences the metabolism of carbohydrates and lipids and causes metabolic dysfunction by retgulating the expression profiles of the key proteins such as PPARγ， C/EBPα， SREBP， and FATP2. Nonalcoholic fatty liver disease （NAFLD） is the most severe manifestation of metabolic dysfunction in the liver， and since both NAFLD and HBV infection can cause liver injury， the research on the interaction between them has attracted more and more attention， with controversies requiring further exploration. Therefore， this article elaborates on the research advances in chronic HBV infection and metabolic dysfunction， so as to provide ideas for subsequent studies.
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Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.
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Objective To observe the impacts of different storage temperatures on the activities of adipose tissues and the extraction and proliferation of adipose-derived stem cells (ADSCs) situated in harvested fat.Methods Adipose tissues obtained by liposuctions in healthy females were kept in different temperature;all groups of adipose tissues were studied in context of the histomorphology and activity of GAPD as well as the extraction efficiency and proliferation of ADSCs.Results Adipose tissues cryopreserved at 4 ℃ within 24 hours could retain their activities effectively,but their activities would decrease rapidly if they preserved at room temperature.The efficiency of adipose tissues extracting stem cells and their proliferations were affected by storage temperatures and times.If adipose tissues were preserved at room temperature for over 1 hour,the extraction efficiency and proliferation of their ADSCs would be lower significantly.Conclusions Adipose tissues cryopreserved at 4 ℃ can effectively ensure their activities and their extraction efficiency and proliferation of ADSCs.It is important to preserve adipose tissues at low temperature after harvesting fat graft.
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Objective To study the impact of maternal high-fat diet during pregnancy and lactation on hepatic steatosis in the early life of offspring rats and its possible mechanism. Methods Female Sprague-Dawley rats were fed either a high fat diet (HF) or control (C) diet for 8 weeks before mating and throughout gestation and ifrst 3 weeks of lactation. The expressions of hepatic fatty acid catabolism related genes, including peroxisome proliferator-activated receptor alpha (PPARα), acyl-CoA syn-thease long-chain family member3 (ACSL3), carnitine palmitoyltransferase-1α(CPT-1α) and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) were determined in offspring liver tissue. The liver pathology was examined in offspring rats at 3 weeks of age. Results Pathohistological ifndings at 3 weeks of age showed that there were diffuse vacuolar degeneration in cytoplasm of hepatocytes and spot necrosis in hepatic lobular in the HF offspring liver. The mRNA expressions of PPARαand Ehhadh genes were markedly increased in the HF offspring as compared to the control group (P<0.05). The mRNA expression of CPT-1αgene was also higher in the HF offspring than that in control group (P=0.19). The level of ACSL3 gene expression, however, was markedly decreased (P<0.05). Conclusions Maternal high fat diet during pregnancy and lactation could result in an increased expression of genes related to hepatic fatty acidβ-oxidation, including PPARα, CPT1αand Ehhadh, but the liver steatosis cannot be reversed in the early life of offspring.
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Objectives To examine the association of the maternal high-fat (HF) diet with increased susceptibility to obe-sity and the development of metabolic diseases in their offspring, and observe difference in the effect of maternal vs. acquired high fat diet on metabolic state in their offspring. Methods A total of 15 SD female rats were divided into HF diet group (group H, n=9) and control diet group (group C, n=6). After fed on different diet for seven weeks, they were mated at the age of ten weeks and became pregnant. Their offspring were then divided to groups CH and HH fed HF diet and groups CC and HC fed control diet. At the age of 3 and 8 weeks, the metabolic markers and the liver pathohistological evidences of their offspring were obtained. Results The body weight, area under curve (AUC) of glucose tolerance, cholesterol and triglyceride were all higher in group H than those in group C (P0.05). At the age of 8 weeks, there was no difference in fasting glucose and insulin levels among the four offspring groups. The AUC and body weight were higher in group H than in group C (main effect of maternal diet, P=0.024, P=0.013). The AUCs were also higher in groups CH and HH than groups CC and HC respectively (main effect of acquired diet, P=0.041). The levels of total cholesterol, triglycerides and LDL at the age of 8 weeks were all higher in HH and CH groups than those in HC and CC groups (main effect of acquired diet, P=0.008, 0.007, 0.000, respectively). Their histological analysis at 8 weeks showed different degrees of fatty liver in HH, HC and CH groups, and normal liver in CC group. Conclusions Maternal HF diet may result in increased body weight, fatty liver and impaired glucose tolerance in their adult offspring, and thus increase the risk of developing metabolic diseases at their later age. .
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Objective To explore the effects of urokinase type plasminogen activator (uPA) gene-modified bone marrow-derived liver stem cells ( BDLSC) transplantation on hepatocyte regeneration in CCl4-induced liver fibrosis rats. Methods Ten male Fisher 344 rats were donor rats of BDLSC. The BDLSC of male rat was transfected with AduPA. Thirty-six female Fisher 344 rats were equally divided into normal group (injected subcutaneously with olive oil) , model group (CCl4 induced the model, injected through tail vein with 0. 9% sodium chloride), BDLSC group (CCl4 induced the model, injected through tail vein with BDLSC) and gene transfected group (CCl4 induced the model,injected through tail vein with gene transfected BDLSC). Liver function and area of collagen were observed. The expression of hepatic growth factor ( HGF) and its receptor c-met mRNA in rats' liver tissues were tested by semiquantitative RT-PCR. The expressions of proliferating cell nuclear antigen (PCNA) in rats' liver tissues were determined by immunohistochemistry staining. Results The areas of collagen in normal group, model group, BDLSC group and gene transfected group was 0. 12% ± 0.03%, 14. 49%±1.40%, 8. 25%±0. 82% and 5. 12%±0. 40% accordingly, there were significant differences between groups (P<0. 05). Compared with model group and BDLSC group, the liver function of gene transfected group significantly improved, the serum levels of hyaluronic acid (HA),procollagen Ⅲ (PCⅢ) and the content of hydroxyproline in liver tissues decreased dramatically. The expression of HGF and c-met at mRNA levels were up-regulated significantly, and the expression of PCNA protein in liver tissues increased obviously. Conclusion uPA gene-modified BDLSC transplantation may induce proliferation of hepatocytes, and then improve the liver functions of fibrotic rats induced by CCl4.
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Objective:To isolate breast cancer stem/progenitor cells from human breast cancer and study their proliferation and differentiation biological characteristics over long-term passages in vitro. Methods:Human breast cancer stem/progenitor cells were enriched in suspension cultures as nonadherent mammospheres(MS). Serial sphere formation assay was performed to determine self-renewal ability of mammosphere-derived cells (MSDC). Differentiation was induced by culturing MSDC in DMEM-F12 supplemented with serum but without growth factors. The ratio of CD44~+/CD24~(-/low) cell population was evaluated by flow cytometry(FCM). Results:The mammospheres were formed after inoculation of primary breast cancer cells into culcutre medium with growth factors but without serum. The mammospheres contained undifferentiated cells similar to stem cells, which had self-renewal and extensive proliferation capabilities. With increasing passages, the cells tended to adhere and differentiate. The number of adhering and differentiating cells increased, and the amount and size of mammospheres decreased. The CD44~+/CD24~(-/low) cell population was enriched in the basal-like molecular subtype of human breast tumors. The biological behaviors of mammospheres varied between different specimens.Conclusion:Cancer cells with stem cell properties of self-renewal, indefinite proliferation and multi-lineage differentiation widely existed in human breast cancer tissues. The biological behaviors varied because of different origin of specimens and changed under the effects of environmental factors.
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Objective To report three cases of fulminant ulcerative colitis (FUC) treated with infliximab (IFX) and the positive result for clinical purpose. Methods Three patients with FUC were infused with IFX (5 mg/kg) at interval of 0, 2, 6 wk. Sulfasalazine or probiotics was used for the maintanance of remission. The mucosal healing was evaluated by endoscopy and patholoic examination. ResultsComplete remission was found in 3 patients with FUC. Eight weeks after IFX withdraw, complete remission was found in two of three cases demonstrated by endoscopy, except for one case died from refractory ventricular tachycardia. The remaing 2 cases showed no active manifestation during 8 months' follow-up. Conclusion IFX therapy results in complete remission in 3 cases with FUC. However, further randomized control study is warranted for concrete evaluation on salty and application clinically.
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Objective To explore the curative effectiveness of transplantation of bone marrow-derived liver stem cells (BDLSCs) transfected with rat interleukin-10 (IL-10) gene in the treatment of liver fibrosis in rats. Methods β2m-/Thy-1+BDLSCs isolated from Wistar rats were transfected with adenovirus-mediated rat IL-10 gene Wistar rats were subcutaneously injected with CCl4 to induce liver fibrosis, and randomly divided into three groups as follows: (1) the model group, infused with 1 ml normal saline (NS); (2) the BDLSC group, infused with NS containing untreated β2m-/Thy-1+BDLSCs (2×105 cells); (3) the IL-10 group, infused with NS containing β2m-/Thy-1+ BDLSCs transfected with IL-10 gene (2×105 cells). Infusion was done via the portal vein. Rats subcutaneously injected with olive oil served as control (the normal group). The BDLCs labeled with diamidine phenylindole dihydrochloride (DAPI) in the liver were localized. Pathological changes and collagen area in liver tissues were observed. Liver function and blood blotting function were tested. Results β2m-/Thy-1+ BDLSCs labeled with DAPI were observed in liver tissues of rats. Significant pathological changes of liver tissues were observed in the model group. Compared with the model group, pathological changes were alleviated to some extent in the BDLSC group. The morphology of liver tissue in the IL-10 group was mostly close to that in the normal group. Collagen deposition of liver tissues was increased obviously in the model group. However, transplantations of untreated and IL-10-transfected BDLSCs both reduced collagen area. Compared with the BDLSC group, collagen deposition was significantly suppressed in the IL-10 group. Transplantation of IL-10-transfected BDLSCs suppressed obviously the levels of ALT, AST, ALP, TBIL, PT and APTT as compared with the model group (P<0. 05). The levels of ALT, TBIL, PT and APTT in the IL-10 group were significantly reduced to the normal levels as compared with those in the BDLSC group (P<0. 05).Conclusions Transplantation of BDLSCs transfected with rat IL-10 gene was effective in treating liver fibrosis in rats. This combined strategy of IL-10 gene and BDLSCs may represent a feasible, effective and safe therapy form for liver fibrosis.
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Objective To investigate the effect of Smad7 gene on the activation of rat hepatic stellate cells (HSCs) in primary culture and on the regulation on gene expression of HSCs. Methods HSCs were isolated from male SD rats by collagenase perfusion of liver from portal vein and by 8.2% Nycodenz gradient centrifugation, and thereby transfected with AdSmad7 and AdGFP (control) respectively. The mRNA expression of transforming growth factor (TGF) ?1, Smad3 and Smad7 were measured by RT-PCR. Meanwhile, Smad7 and ?-smooth muscle actin (?-SMA) expressions were detected by immuno- cytochemistry. Results The expression of Smad7 mRNA in AdSmad7 group increased remarkably compared with TGF?1 control group, while the expression of Smad3 and TGF?1 mRNA remains unchanged. The expression of Smad7 protein was significantly higher in AdSmad7 group than that in other three groups. Accordingly, the expression of ?-SMA protein in the group of HSCs transfected with AdSmad7 was the lowest(P
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Objective The author investigated the clinical features of the the patients with acute pancreatitis and hyperlipaemia (hypertriglyceridaemia),in order to intensify the knowledge of the condition.Methods Forty-three patients with acute pancreatitis were randomly selected and assigned into 2 grups,i.e.,those with hyperlipaemia (11cases) and those with billiary type (32 cases).Results Among the 43 cases,7 were acute necrotizing pancreatitis (5 in hyperlipaemia group).Enumeration correlation demonstrated significant positive correlation between hyperglyceridaemia and the necrotizing type of acute pancreatitis (? 2=6.58,P)or diabetics were significantly higher in hyperglyceridaemia group than in acute billiary pancreatitis group, and so was the life-threatening complications.Conclusion ①Hyperglyceridaemia bears significant positive correlation to the necrotizing type of acute pancreatitis and its life-threatening complications as well.②Diet control,reducing body weight and application of anti-hyperlipaemia drugs will be helpful in prevention and treatment of the relapse of the disease.
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Objective:To determine vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 expression in pancreatic carcinomas and the relationship of the expression of VEGF-C and VEGFR-3 with lymph angiogenesis and lymphatic metastasis.Methods:Specimens of pancreatic carcinoma were immunohistochemically stained for VEGF-C and VEGFR-3. Lymphatic vessels were displayed by immunohistochemical double staining.And lymphatic vessel density (LVD) were counted.The correlations among VEGF-C expression,VEGFR-3 expression and LVD in tumors with or without lymph node metastasis were statistically analyzed.Results:VEGF-C expression was observed in the cytoplasm of carcinoma cell,and VEGFR-3 expression was observed in the cytoplasm of endothelial cell of lymphatic and micro vessel.The VEGF-C expression rate,VEGFR-3 expression rate and LVD of tumors with lymph node metastasis were higher than those of tumors without lymph node metastasis.LVD correlated with the expression of VEGF-C and VEGFR-3.Conclusion:The high expressions of VEGF-C and VEGFR3 in pancreatic carcinomas suggest their involvement in lymph angiogenesis.VEGF-C,VEGFR-3 and LVD are associated with lymphatic metastasis and may besignificant prognostic factors for lymphatic metastasis in pancreatic carcinomas.This implies that it is an effective option to control lymphatic metastasis of pancreatic carcinomas to inhibit the effect of VEGF-C or VEGFR-3.