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ObjectiveTo investigate the differentially expressed proteins in the plasma exosome of acute-on-chronic liver failure (ACLF) patients with different prognoses, to analyze their functions and biological processes, and to provide a basis for clinical diagnosis. MethodsA prospective study was performed for 10 ACLF patients who were hospitalized and diagnosed in Beijing YouAn Hospital, Capital Medical University, from July 2019 to October 2019, and the patients were followed up for 90 days. The patients who died or received liver transplantation were enrolled as liver transplantation/death group (5 patients), and the patients who survived were enrolled as survival group (5 patients). The Mann-Whitney U test was used for comparison of general data between the two groups. The label-free quantitative proteomic method was used for identification and quantitative analysis of plasma exosome proteins to screen out differentially expressed proteins, and a functional enrichment analysis was performed. R-3.5.1 software was used to perform a hierarchical cluster analysis of differentially expressed proteins to analyze the biological processes involving these proteins. ResultsA total of 860 proteins were identified by the exosome proteomic analysis, and according to the criteria of upregulation ＞1.2 folds or downregulation ＞1.2 folds (P＜0.05), there were 116 differentially expressed proteins. Compared with the liver transplantation/death group, the survival group had 62 upregulated proteins and 54 downregulated proteins. The bioinformatics analysis showed that these differentially expressed proteins mainly participated in immune reaction, signal transduction, vesicle-mediated transport, cell death, and cell proliferation and were closely associated with the signaling pathways including inflammatory response, carbohydrate and amino acid metabolism, hepatocyte injury, and hepatocyte regeneration. ConclusionDifferentially expressed proteins screened out by the label-free quantitative proteomic method can be used as serological markers for the early diagnosis and prognostic evaluation of ACLF.
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Objective@#To investigate the endoplasmic reticulum stress (ERS) role in the course of liver failure induced by severe hepatitis B virus (HBV) infection and its related mechanism.@*Methods@#Liver tissue samples and clinical data [chronic hepatitis B patients (12 cases, chronic hepatitis B group), hepatic failure induced by severe hepatitis B virus (12 cases, severe hepatitis B virus liver failure group), and normal subjects (8 cases, control group)] were collected from the Beijing You'an Hospital affiliated to Capital Medical University between 2009 to 2011. Statistical analysis was performed on the clinical indicators of each group. The structure of endoplasmic reticulum in liver tissue was observed by transmission electron microscopy. Western blot and qRT-PCR were used to detect the expression of endoplasmic reticulum stress and apoptosis-related factors, including glucose-regulated protein (Grp), and C/EBP homologous protein (CHOP). Frozen sections of liver tissues were prepared for immunofluorescence test. All data were expressed as mean ± standard deviation. LSD-t test was used to compare the results between groups. A p value < 0.05 was considered as statistically significant.@*Results@#Transmission electron microscopy showed that the morphological structure of the endoplasmic reticulum was damaged in both groups (chronic hepatitis B and liver failure induced by severe hepatitis B virus), and liver failure induced by severe hepatitis B virus group was more critical. Western blot and qRT-PCR showed that Grp78, Grp94 and Caspase-4 were highly expressed in normal group and chronic hepatitis B group, and the relative protein expressions were 1.20 ± 0.13 and 0.78 ± 0.11, 0.90 ± 0.06 and 0.11 ± 0.01, 0.15 ± 0.02 and 0.22 ± 0.04, respectively. The expression of protein was weakened in liver failure induced by severe hepatitis B virus group (relative protein expression was 0.01 ± 0, 0.01 ± 0, and 0.11 ± 0.02, respectively).There was a statistically significant difference between the two groups (P < 0.05). The expression of CHOP was consistent with the results of immunofluorescence, and increased with the stressing of injury.@*Conclusion@#During the course of severe hepatitis B infection, dysregulated endoplasmic reticulum stress activated mild stress in chronic hepatitis B group, while severe stress in hepatic failure induced by severe hepatitis B virus group. Therefore, endoplasmic reticulum stress plays an important and complex role in the pathogenesis of hepatic failure induced by severe hepatitis B virus.
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Objective@#To understand the relations between high risk sexual behavior and HIV infection among MSM in ways of finding male partners in Ningbo.@*Methods@#A cross-sectional study was conducted in Ningbo between April and November in 2018. Data related to socio-demographics, ways of finding male partners, adoption of gay apps and sexual behaviors were collected by snowball method. Blood samples were drawn for HIV antibody testing. Classified data was evaluated by chi-square test. Related factors on HIV infection were analyzed by multivariate logistic regression.@*Results@#A total of 735 participants were included in this study. Ways of finding male partners would through gay apps (60.8%, 447/735), QQ/Wechat (32.3%, 237/735) and gay-places (6.9%, 51/735). Related information on high risk sexual behavior and HIV infection among gay apps users were found as: 16.8%(75) had sexual behavior once per week in the past 6 months, 41.8% (187/447) had multiple sexual partners, 12.1% (54/447) had unprotected anal intercourse in the last time, 52.3% (234/447) having had unprotected anal intercourse in the past 6 months. The overall HIV prevalence rate was 12.1%(54/447). Among the HIV cases who got infected within the two years, 68.6%(24/35) of them had used gay apps for less than two years. Results from the, multivariate logistic regression analysis showed that gay apps users were more susceptible to infected HIV than those who used the QQ/Wechat (OR=3.03, 95%CI: 1.30-7.07).@*Conclusions@#Gay apps was popularly known among the Ningbo MSM, and was associated with the high risk sexual behaviors and HIV infection. HIV control and prevention programs should be strengthened in the MSM population who used the gay apps. Related surveillance and intervention programs for MSM, who use the gay apps, need to be further reinforced.
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Objective To investigate the expression of apoptosis stimulating protein two of p53 (ASPP2) in acute kidney injury (AKI) induced by carbon tetrachloride (CCl4) in mice. Methods Thirty-two male Balb/c mice were randomly divided into olive oil control group (control group, 8 mice) and CCl4 experimental group (experimental group, 24 mice). A mouse model of AKI was induced by a single high-dose abdominal injection of CCl4. The mice in the experimental group were sacrificed at 12 h, 24 h and 48 h after CCl4 injection. The mice in the control group were sacrificed 24 h after treatment. The serum and kidney tissue samples were collected. Serum biochemical indicators [serum creatinine (Scr) and urea nitrogen (BUN)] were measured by automatic biochemical analyzer. The pathological damage of kidney tissue was observed by hematoxylin-eosin (HE) staining and Periodate-Schiff (PAS) staining. ASPP2 positioning and expression level were observed by immunohistochemistry. The apoptosis of mouse kidney tissue was detected by in situ apoptosis. The expression of ASPP2 protein and ASPP2 mRNA in renal tissue were detected by Western blotting and quantitative real-time PCR. Results Compared with the control group, the levels of Scr and BUN were significantly increased in the experimental group (P＜0.01). Histopathology showed partial renal tubular brush margin detachment, renal tubular epithelial cell necrosis and nuclear disintegration in the experimental group. TUNEL staining showed that the apoptosis rate of renal tissue cells increased significantly in the experimental group (P＜0.01). Compared with the control group, the expression of ASPP2 in the experimental group increased at the early period and then decreased with the prolongation of injury time. The mRNA expression was consistent with the protein expression, and all reached the peak after 24 hours injury (P＜0.01). Immunohistochemistry showed that ASPP2 was mainly localized in the cytoplasm of renal tubular epithelial cells. Conclusions A single high-dose injection of CCl4 in the abdominal cavity can induce AKI in mice. The expression of ASPP2 is consistent with the degree of renal tissue damage. As the damage of renal tissue is aggravated, the expression of ASPP2 is gradually increased, which indicates that ASPP2 may be a damage factor.
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Apoptosis stimulating protein of p53 2 (ASPP2) is a member of the apoptosis stimulating proteins of p53 and can specifically bind to the core region of p53 protein and enhance the ability of p53 to promote transcription of apoptotic genes. At present, it is believed that ASPP2 plays an important role in regulating cell apoptosis, autophagy, proliferation and affecting the progression of inflammation and tumors. This article summarizes the main biological functions of ASPP2 and the research advances in the role of ASPP2 in hepatocellular carcinoma, hepatitis C, and nonalcoholic fatty liver disease. Studies have shown that ASPP2 can regulate cell apoptosis and may be a potential therapeutic target for a variety of diseases.
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Objective@#To investigate the role of the glycogen synthase kinase 3β (GSK3β) and the peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway in acute liver failure and related mechanisms in a mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS).@*Methods@#C57BL/6 mice were given intraperitoneal injection of D-GalN/LPS to establish a mouse model of acute liver failure. SB216763 was used to inhibit the activity of GSK3β and PPARα siRNA was used to inhibit the expression of PPARα. Western blotting was used to measure the expression of PPARα protein. The changes in liver pathology were observed to evaluate liver injury, and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to assess liver function. Quantitative real-time PCR was used to measure the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12p40 (IL-12p40), and PPARα. A one-way analysis of variance was used for comparison of means between multiple groups; the least significant difference test was used for data with homogeneity of variance, and the Games-Howell method was used for data with heterogeneity of variance.@*Results@#In the mice with liver failure induced by D-GalN/LPS, GSK3β inhibition promoted the mRNA and protein expression of PPARα (F = 13.18 and 301.36, P = 0.00 and 0.00). In the mice with acute liver failure induced by D-GalN/LPS, GSK3β inhibition alleviated liver bleeding, inflammation, and necrosis and reduced the serum levels of ALT (F = 25.16, P = 0.000) and AST (F = 12.96, P = 0.001), as well as the mRNA expression of TNF-α (F = 32.17, P = 0.00), IL-1β (F = 11.57, P = 0.005), and IL-12p40 (F = 14.17, P = 0.015) in liver tissue. The inhibition of PPARα expression reversed the liver-protecting effect of GSK3β inhibition, which manifested as aggravation in liver bleeding, inflammation, and necrosis, increases in the serum levels of ALT (F = 25.16, P = 0.001) and AST (F = 12.96, P = 0.000), and an increase in the mRNA expression of TNF-α (F = 32.17, P = 0.00), IL-1β (F = 11.57, P = 0.024), and IL-12p40 (F = 14.17, P = 0.001) in liver tissue.@*Conclusion@#In mice with acute liver failure induced by D-GalN/LPS, the GSK3β-PPARα-inflammatory factor signaling pathway may play an important role. GSK3β inhibition has a protective effect in mice with acute liver failure possibly by activating the inhibitory inflammatory factor of PPARα.
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Objective@#To investigate the effect of calcium-independent phospholipase A2 (iPLA2) inhibitor in reducing hepatocyte lipoapoptosis and improving insulin resistance.@*Methods@#A total of 28 male Sprague-Dawley rats were randomly divided into the following three groups: 12 rats in group I (normal control group) were given normal diet for 18 weeks; 8 rats in group II (non-alcoholic fatty liver disease model group) were given high-fat diet for 18 weeks; 8 rats in group III (iPLA2 inhibitor group) were given high-fat diet for 18 weeks and intraperitoneal injection of the iPLA2 inhibitor bromoenol lactone 150 μg/kg once every other day since week 15 (14 times of injection in total). All the rats were sacrificed at the same time, and body weight and liver weight were measured. Blood lipids, serum enzymes, fasting blood glucose, fasting insulin, free fatty acid, and serum iPLA2 concentration were measured in each group, and liver pathological changes were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the level of hepatocyte apoptosis and the apoptotic index was calculated. Quantitative PCR was used to measure the mRNA expression of iPLA2. The Student-Newman-Keuls test and the chi-square test were used for comparison of parameters between groups I, II, and III. P < 0.05 was considered statistically significant.@*Results@#Compared with group I, group II had significant increases in triglyceride (0.75±0.05 mmol/L vs 1.20±0.13 mmol/L, P < 0.05), cholesterol (1.50±0.12 mmol/L vs 2.94±0.34 mmol/L, P < 0.05), low-density lipoprotein (0.65±0.06 mmol/L vs 1.30±0.16 mmol/L, P < 0.05), free fatty acid (0.58±0.09 mEq/L vs 0.80±0.20 mEq/L, P < 0.05), fasting blood glucose (4.85±0.22 mmol/L vs 6.94±0.65 mmol/L, P < 0.05), and fasting insulin (0.89±0.52 mmol/L vs 1.29±0.52 mmol/L, P < 0.05), and a significant reduction in the insulin sensitivity index (0.52±0.21 vs 0.27±0.11, P < 0.05); group II also had significant inflammation and fatty degeneration shown by liver pathology, and compared with group I, group II had significant increases in apoptotic cells and apoptotic index (0.58%±0.17% vs 39.69%±4.96%, P < 0.05). Compared with group I, group II had significant increases in serum iPLA2 concentration (2.92±0.08 ng/ml vs 3.28±0.14 ng/ml, P < 0.05) and the mRNA expression of iPLA2 in the liver (1.07±0.18 vs 7.68±0.49, P < 0.05). Compared with group II, group III had a lower level of hepatocyte apoptosis, a significant reduction in apoptotic index (39.69%±4.96% vs 24.80%±2.53%, P < 0.05), significant reductions in serum iPLA2 concentration (3.28±0.14 ng/ml vs 2.64±0.24 ng/ml, P < 0.05) and the mRNA expression of iPLA2 in the liver (7.68±0.49 vs 2.60±0.36, P < 0.05), significant reductions in fasting insulin (1.29±0.52 mmol/L vs 0.80±0.09 mmol/L, P < 0.05) and fasting blood glucose (6.94±0.65 mmol/L vs 5.18±0.35 mmol/L, P < 0.05), and a significant increase in insulin sensitivity index (0.27±0.11 vs 0.45±0.09, P < 0.05).@*Conclusion@#There is a significant increase in the expression of iPLA2 in rats with non-alcoholic fatty liver disease, and iPLA2 inhibitor can reduce hepatocyte lipoapoptosis and improve insulin resistance.
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Objective To understand the epidemiology characteristics and survival status of HIV/AIDS patients with access to highly antiretroviral therapy (HAART) in Ningbo during 2004-2015.Methods A retrospective cohort study was conducted among HIV/AIDS patients diagnosed between 2004 and 2015.Life Tables were used to estimate survival rates,and Kaplan-Meier curve with Log rank test were used to describe the survival curves and the Cox proportional hazard model was used to determine predictors of mortality.Results Of the subjects,the median age when starting HAART was 35 years (IQR:27-45 years).Most of them were males,local residents,married,infected through heterosexual sexual transmission,and their baseline CD4 T cells counts were mainly ≤ 200 cells/μ 1,and most of them were at clinical stage Ⅰ (WHO).The cumulative survival rate was 96.75％ for the first year,92.36％ for the fifth year,91.87％ for the seventh year and 90.02％ for the tenth year.The risk of the mortality was 17.34 times higher for those aged ＞60 years compared with those aged ≤20 years (95％ CI:2.11-142.71),2.83 times higher for those at clinical stage ⅣV (WHO) compared with those at clinical stage Ⅰ (WHO) (95％CI:1.67-4.80) and 3.26 times higher for those with drug resistance compared with those without drug resistance (95％ CI:1.77-6.01).Blood transmission,lower CD4 + T cell level,BMI ＜ 18.5,unmarried were the risk factors for the mortality.Conclusions The effect of HAART was obvious in the HIV/AIDS patients in Ningbo,their survival rate was high.The finding indicated that it is necessary to strengthen the health care for old population and health education about AIDS prevention and control,and conduct large scale screening.Early discovery,early diagnosis,early treatment and improving treatment compliancy are still the effective ways to reduce the mortality.
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Objective To understand the epidemiology characteristics and survival status of HIV/AIDS patients with access to highly antiretroviral therapy (HAART) in Ningbo during 2004-2015.Methods A retrospective cohort study was conducted among HIV/AIDS patients diagnosed between 2004 and 2015.Life Tables were used to estimate survival rates,and Kaplan-Meier curve with Log rank test were used to describe the survival curves and the Cox proportional hazard model was used to determine predictors of mortality.Results Of the subjects,the median age when starting HAART was 35 years (IQR:27-45 years).Most of them were males,local residents,married,infected through heterosexual sexual transmission,and their baseline CD4 T cells counts were mainly ≤ 200 cells/μ 1,and most of them were at clinical stage Ⅰ (WHO).The cumulative survival rate was 96.75％ for the first year,92.36％ for the fifth year,91.87％ for the seventh year and 90.02％ for the tenth year.The risk of the mortality was 17.34 times higher for those aged ＞60 years compared with those aged ≤20 years (95％ CI:2.11-142.71),2.83 times higher for those at clinical stage ⅣV (WHO) compared with those at clinical stage Ⅰ (WHO) (95％CI:1.67-4.80) and 3.26 times higher for those with drug resistance compared with those without drug resistance (95％ CI:1.77-6.01).Blood transmission,lower CD4 + T cell level,BMI ＜ 18.5,unmarried were the risk factors for the mortality.Conclusions The effect of HAART was obvious in the HIV/AIDS patients in Ningbo,their survival rate was high.The finding indicated that it is necessary to strengthen the health care for old population and health education about AIDS prevention and control,and conduct large scale screening.Early discovery,early diagnosis,early treatment and improving treatment compliancy are still the effective ways to reduce the mortality.
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Autophagy is a pathway of intracellular degradation, in which autophagic vacuoles are formed to transport intracellular biomacromolecules and damaged organelles to lysosomes. Autophagy plays an important role in the maintenance of the dynamic balance of liver function. Abnormal liver cells can be eliminated by autophagy. This article reviews the close relationship of autophagy with the proliferation of liver cells, non-parenchymal liver cells, and hepatic stem cells. Analysis has shown that autophagy may restore the volume and function of the liver by promoting the proliferation of liver cells and hepatic stem cells, which can be stopped in time to prevent tumor development. Autophagy may promote the activation of non-parenchymal liver cells during liver dysfunction, which can inhibit the regeneration of liver cells, and, in the meantime, lead to the development and progression of liver fibrosis. When the tumor is being formed, autophagy plays an important role in the transformation of normal cells into cancer cells; malignant regeneration of liver cells is activated but not terminated in time.
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Objective To analyze the role of cysteinyl aspartate specific proteinase-1 (caspase-1) in a mouse model of D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced acute liver failure (ALF) and to study the possible mechanism. Methods C57BL/ 6 mice were randomly divided into four groups including control group, Z-WEHD-FMK (caspase-1 inhibitor) treatment group, ALF model group and Z-WEHD-FMK-treated ALF group. The mouse model of ALF was established by intraperitoneally injec-ting the mice with D-GalN (450 mg/ kg) and LPS (10 μg/ kg). The damages in liver tissues were evaluated based on the histopathological examination and the levels of alanine transaminase (ALT) and aspartate trans-aminase (AST) in serum samples. Western blot assay was performed to analyze the expression of caspase-1 and the phosphorylation of glycogen synthase kinase 3β (GSK-3β). The qRT-PCR was used to measure the expression of inflammatory cytokines at transcriptional level. Results The expression of caspase-1 at both mRNA and protein levels were gradually increased during the development of ALF. Compared with the mice with ALF, those in the Z-WEHD-FMK-treated ALF group showed less severe liver damages on histopatholog-ical examination and decreased levels of ALT and AST in serum samples [ALT: (479. 2±39. 5) U/ L vs (998. 5±60. 4 ) U/ L, P<0. 05; AST: ( 478. 5±28. 6) U/ L vs ( 1 180. 7±91. 4) U/ L, P<0. 05]. The expression of TNF-α, IL-1β, IL-18 and IL-33 at transcriptional level were significantly suppressed in mice with ALF upon the Z-WEHD-FMK intervention. Results of the Western blot assay indicated that Z-WEHD-FMK suppressed the activities of GSK-3β by enhancing its phosphorylation. Conclusion This study demon-strated that caspase-1 could promote the activation of GSK-3β resulting in the development of inflammation responses and liver damages during the development of ALF in mice.
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ObjectiveTo investigate the role and action mechanism of Ganshuang granules in the protection against CCl4-induced chronic liver injury in mice via autophagy, and to provide a basis for its clinical application. MethodsWe established a chronic liver injury model in mice by intraperitoneal injection of CCl4, and a cell model of liver damage in cell line HL-7702 induced by CCl4 in vitro. The animals were divided into three groups, Ganshuang granule intervention group, normal control group, and CCl4 group without receiving Ganshuang granules. In addition, we exposed the cells to 3-methyladenine (3-MA), an autophagy inhibitor, and observed the effects of Ganshuang granules on cell apoptosis. Liver tissue injury was evaluated by HE staining; serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined by biochemical assays. Autophagy was assessed by immunofluorescence staining and Western blotting. Liver apoptosis was analyzed by flow cytometry and Annexin V/PI double staining. Comparisons between groups were performed using analysis of variance. ResultsHE staining showed that liver tissue injury was significantly milder in the Ganshuang granule intervention group than in the CCl4 group. Serum ALT and AST levels were significantly differences between Ganshuang granule intervention group, normal control group, and CCl4 group (F=1576、1335，P＜005). Both in vivo and in vitro tests showed that autophagy increased significantly in cells treated with Ganshuang granules than in cells exposed to CCl4 alone, while apoptosis was significantly reduced in the former. The administration of 3-MA weakened the protective effect of Ganshuang granules and increased apoptosis. Flow cytometry showed that apoptosises were significiantly differences between five groups (F=25637,P＜001). ConclusionGanshuang granules have protective effects against chronic liver injury by inhibiting apoptosis, possibly through enhanced autophagy.
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Objective To investigate the effects of peroxisome proliferator-activated receptor α( PPARα) on macrophage-mediated inflammatory responses with the interference of lipopolysaccharide and the possible mechanism.Methods The bone marrow stem cells were isolated from the femora of mice.The granulocyte-macrophage colony stimulating factor ( GM-CSF) was used to stimulate the in vitro differentiation from bone marrow stem cells into primary macrophages.An in vitro model with cultured cells expressing in-flammatory cytokines was established by treating the primary macrophages with lipopolysaccharide ( LPS) .A specific chemical agonist, Wy-14643, was used to activate PPARα. Autophagy inhibitors including 3-methyladenine (3-MA) and small interfering RNA against Atg7 ( Atg7 siRNA) were used to inhibit the autophagy.Western blot assay was performed to detect the expression of autophagy-related proteins ( Atg5, Atg7, Beclin-1 and LC3).The transcriptional levels of TNF-α, IL-1β, IL-6, Atg5, Atg7 and Beclin-1 were analyzed by qRT-PCR.Results Compared with the macrophages treated with LPS alone, those pretreated with various concentrations of Wy-14643 (10 μmol/L, 25 μmol/L and 50 μmol/L) showed inhibited ex-pression of proinflammatory cytokines ( TNF-α,IL-1βand IL-6) and enhanced expression of autophagy-relat-ed proteins (Atg5, Atg7 and Beclin-1) at mRNA level in a dose-dependent manner.The expression of auto-phagy-related proteins (Atg5, Atg7, Beclin-1 and LC3) by macrophages was promoted with the pretreatment of Wy-14643 as indicated by Western blot assay.The transcriptional levels of TNF-α, IL-1βand IL-6 were increased in Wy-14643 pretreated-macrophages after stimulation with 3-MA or Atg7 siRNA .Conclusion PPARαsuppressed the macrophage-mediated inflammatory responses by promoting autophagy, suggesting that the PPARα-autophagy pathway might be one of the signaling pathways regulating LPS induced-inflamma-tory responses.
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<p><b>OBJECTIVE</b>To investigate the protective mechanism of endoplasmic reticulum stress (ERS) inhibition against inflammation-induced acute liver injury using a mouse model.</p><p><b>METHODS</b>Marrow-derived stem cells were isolated from mouse femur and used to derive macrophages for analysis in experimental inflammation conditions, established by exposure to LPS and consequent activation of TLR4. Tunicamycin, an ERS chemical inducer, was applied to interfere the inflammation model condition.Affect on the inflammation-related factor MAPK was detected by western blot, and affects on gene expression of inflammatory factors were measured by real-time quantitative PCR. Affect on TNFa was also measured by ELISA.</p><p><b>RESULTS</b>Expression of TNFa, IL-6 and IL-1b was induced upon exposure to LPS, with the peak levels being reached at 4 hours of exposure (TNFa, 0.82+/-0.24; IL-1 b, 2.20+/-0.69; IL-6, 0.330+/-0.150). Tunicamycin significantly enhanced the LPS-induced up-regulation of TNFa, IL-6 and IL-1b expression (TNFa, 1.44+/-0.38, t=2.8, P<0.05; IL-1b, 16.063.40, t =7.93, P<0.05; IL-6, 31.1610.60, t=5.08, P<0.05). The tuniamycin treatment also enhanced the LPS-induced up-regulation of the protein expression of phospo-p38, phospho-JNK and phoshpo-ERK.</p><p><b>CONCLUSION</b>ERS collaborates with LPS to promote the TLR4-mediated inflammatory response of macrophages, and this collaboration may be a pathogenic mechanism underlying progressive development of acute liver injury.</p>
Subject(s)
Animals , Mice , Disease Models, Animal , Endoplasmic Reticulum Stress , Inflammation , Interleukin-6 , Lipopolysaccharides , Liver , Macrophages , Toll-Like Receptor 4 , Up-RegulationABSTRACT
In order to optimize the fabrication of SiO2 tubes immobilized with antibody for hepatitis C virus antigen (HCAg) detection, we formed the activated amino on the surface of SiO2 tubes by using the activation of aminosilane. Then we immobilized the hepatitis C virus (HCV) monoclonal antibody on the surface of SiO2 tubes by using glutaraldehyde as a chemical cross-linker, followed by detecting HCAg. Sequence tests showed that when the SiO2 tubes were treated in 10% (V/V) aminosilane solution and 3% (V/V) glutaraldehyde solution for 3 hours and 2 hours, respectively, the HCV monoclonal antibody had high immobilization efficiency and low nonspecificity, and the HCAg was detected to 1 ng/mL. This experiment can provide principle and experimental data for establishment of HCAg magnetic immunoassay system.
Subject(s)
Humans , Antibodies, Immobilized , Allergy and Immunology , Antibodies, Monoclonal , Chemistry , Allergy and Immunology , Hepatitis C Antibodies , Chemistry , Allergy and Immunology , Hepatitis C Antigens , Allergy and Immunology , Silicon Dioxide , ChemistryABSTRACT
Objective To discuss the efficacy and safety of transurethral plasmakinetic resection of the prostate(PKRP) for benign prostatic hyperplasia(BPH).Methods A British made Bipolar plasmakinetic resection system(Gyrus) was employed in this series.Started from the 6 o’clock point,the middle lobe of the prostate was resected,followed by the left and right lobes,which were resected down to the prostate capsule.And then the bladder neck was cut down.The apical tissues were resected to the anterior border of the seminal colliculus.After the operation,a F22 three-channel catheter was indwelled for 3 to 5 days after the operation,and a balloon was place in the bladder neck.Results The procedure was completed successfully in all of the cases with a mean operation time of(85.0?12.0) min,and a median blood loss 115.0 ml(30 to 650).Ten patients received blood transfusion during the operation(200 to 400 ml).No case showed transurethral resection syndrome or obturator nerve reflex.Fourteen patients developed inflammatory stricture of the anterior ureter and was then cured by dilating the urinary tract;15 cases showed transient urinary incontinence and was cured after pelvic floor muscle training for 1 to 3 weeks.Follow-up was available in the patients for 1 to 6 months,during which the mean Qmax of the patients significantly increased compared to that preoperation [from(7.6?2.4) ml/s to(22.6?3.4) ml/s,t=13.582,P=0.000),and the IPSS and life quality score markedly decreased [from 27.3?1.5 and 4.3?0.4 to 7.0?1.2 and 2.1?0.8;t=16.394 and 9.761,P=0.000 and 0.005,respectively] Conclusion PKRP is an effective and safe treatment for BPH.