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Objective To explore the regulatory effects of cucumin onoxidation and antioxidation in non-alcoholic steatohepatitis (NASH ) .Methods Fifty-six clean male rats were randomly divided into 7 groups by random numbers table .Eight rats in normal control group were fed by normal diet for 12 weeks .Twenty-four rats in model group were fed by choline dificinet (CD) diet and randomly sacrificedat week 4 ,8 and 12 with 8 rats each time point .Twenty-four rats incucumin treatment group were given cucumin at high (500 mg/[kg · d]) ,medium (100 mg/[kg · d]) and low (50 mg/[kg · d]) dosages with 8 rats each dosage from week 5 of CD diet for 8 weeks ,and the rats were sacrificed at week 12 .The liver tissues were reserved for pathology test and detections of thiobarbituric acid reactive substances (TBARS) ,glutathione (GSH) ,the activities of superoxide dismutase (SOD) ,manganese superoxide dismutase (MnSOD) ,glutathione peroxidase (GPx) ,and levels of triglyceride (TG) and total cholesterol (TC) .The measurement data with normal distribution were analyzed using t test ,and the data with non-normal distribution were analyzed using rank sum Z test .Results The liver of rats presented with the performance of NASH when fed with CD diet for 4 weeks ,and presented with early fibrosis after 8 weeks of CD diet ,even progressed to cirrhosis after 12 weeks of CD diet .The NAS scores of medium and high dose curcumin treatment groups were 6 .50 (5 .25 ,7 .00) and 6 .00 (5 .00 ,6 .75) ,respectively ,which were both lower than that model group at week 12 (8 .00 [7 .00 ,8 .00])(Z=2 .441 and 2 .728 ,respectively , both P< 0 .01) ,while fibrosis stages at week 12 were not significantly different compared with model group (Z=0 .795 and 1 .807 ,respectively ,both P> 0 .05) .TG and TC levels in liver tissues of rats in low ,medium and high doses treatment group were not significantly different compared with model group at week 12(TG :t=0 .54 ,1 .18 and 1 .66 ,respectively ;TC :t=0 .11 ,0 .59 and 0 .62 ,respectively ;all P>0 .05) .The GSH contentin liver of rats in high dose group was (1185 .82+204 .01) mg/g ,which was significantly different from that in model group at week 12 (735 .29 + 35 .08) (t=4 .97 ,P<0 .01) .The TBARS contents in the liver of the middle and high doses curcumin treatment group were significantly different from that of model group at week 12 (t=7 .58 and 11 .62 ,respectively ,both P< 0 .01) .The SOD activities in liver of rats in low ,medium and high doses curcumin treatment group were statistically different from that in model group (t=4 .17 ,4 .32 and 6 .10 ,respectively ,all P<0 .01) .MnSOD activity in liver of rats in high dose group was significantly different from model group at week 12 (t=8 .42 ,P<0 .01) .The live GPx contents in low ,medium and high doses curcumin treatment group were all not significantly different from that in model group at week 12 (t=0 .27 ,0 .21 and 0 .60 ,respectively ,all P>0 .05) .Conclusions CD diet in SD rats could induce hepatic lipid deposition in liver ,and cause liver antioxidative system disorders ,GSH exhaustion ,and decreases of SOD and GPx activities .Curcumin treatment could improve liver NAS score of NASH rats ,and might play a protective role by upregulating the SOD activity and increasing liver GSH content .But curcumin has no effects on liver GPx activity and fat deposition in liver of NASH rats .
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Objective To investigate the changes of A20 expression stimulated by free fatty acids (FFA) and its pathway.Methods HepG2 cells and U937 cells were stimulated by 0.5 mmol/L mixed FFA.The expression of A20,phosphor-p65 and phosphor-IκBα of neclear factor (NF)-κB pathway and phosphor-c-Jun N-terminal kinase (JNK),JNK,phosphor-extracellular signal-regulated kinase (ERK),ERK,phosphor-p38 and p38 of mitogen-activated protein kinase (MAPK) pathway were detected by Western blotting.The level of interleukin (IL)-12p,IL-1β,tumor necrosis factor (TNF)-α,IL-6,IL-10 and IL-8 cytokines in the supernatant of cell culture were detected by flow cytometry.T-test was performed for statistical analysis.Results The level of A20 changed along with the stimulated time of FFA.NF-κB and MAPK pathways were activated after FFA stimulation.The secretion of IL-6 and IL-8 increased after HepG2 cells stimulated by FFA and both reached peak at 24 hour.Compared with control group,the difference in IL-8 was statistically significant ((423.8 ± 8.9) pg/mL vs (12.4 ± 4.5) pg/mL,t=41.28,P＜0.01).The difference in IL-6 was also statistically significant ((4 082±423.6) pg/mL vs (52.9±29.5) pg/mL,t=9.49,P＜0.01).After U937 cells were stimulated by FFA,the secretion of IL-8 increased compared with control group.And in a certain period of time the secretion was time dependence.The maximum secretion of 24 hours was (200.6±5.7) pg/mL vs (5.0±3.9) pg/mL,and the difference was statistically significant (t=28.16,P＜0.01).IL-10,IL-12p,IL-1β and TNF-α were detected.Both NF-κB pathway and MAPK pathway were detected.Conclusions The in vitro FFA mediated steatotic cell model could induce the expression change of A20 and secretion of inflammatory cytokines.NF-κB and MAPK pathways involved in the response to FFA in HepG2 cells and U937 cells.
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Objective To explore the effect of health check-up on screening and early detection of colorectal or breast cancer.Methods A total of 4 179 health check-up receivers were enrolled in this investigation.Basic health information was linked to the Shanghai Cancer Registry System and confirmed cancer diagnosis through Access 2007.Excel 2013 was used to analyze cancer detection rate,ranking,age and sex distribution and early stage proportion.Results During 2011 and 2012,81 cancer cases were identified,with a detection rate of 47.47/100 000.The highest detection rate was found in 60-69 years old group (105.36/100 000),and male:female ratio was 1.25 ∶ 1.One colorectal cancer was diagnosed,resulting in a detection rate of 0.79/100 000.Eleven breast cancers were diagnosed,with a detection rate of 17.22/100 000.Early stage breast cancer accounted for 71％,which was higher than average level between 2005-2009 (33％).Conclusion Detection rate of colorectal cancer among health check-up receivers was very low,which is inconsistent with the high incidence of colorectal cancer in Shanghai.Fecal occult-blood test should be performed during health check-up,which may increase colorectal cancer detection.Moreover,health check-up may contribute to early detection of breast cancer.
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Objective To discuss current detection of food intolerance in health check-up populations and the influence of food intolerance on immune system and inflammation parameters.Methods Serum levels of 14 kinds of food-specific IgG antibodies were analyzed by using enzyme linked immunosorbent assay (ELISA) among 257 healthy check-up adults.White blood cell count,eosinophils,globulin,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),rheumatoid factor (RF),antinuclear antibodies (ANA) and T cell function were compared between the positive group and the negative group.Student's t test and Chi-square test were used for data analysis.Results Food-specific IgG antibodies were found in 134 participants (52.14％).The most common intolerant foods were egg,crab and milk.Moderate to severe food intolerance was caused by egg or milk.There was significant difference in eosinophils and serum globulin between the positive and the negative group (t =-0.07,x2 =8.91,both P ＜0.05).However,no difference was observed in white blood cell count,ESR,CRP,RF,ANA and T cell function between two groups (all P ＞ 0.05).Conclusion Eosinophils and serum globulin may significantly increased in people with food intolerance,although white blood cell count,ESR,CRP,RF,ANA and T cell function could be normal.
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ObjectiveTo explore the role of fatty acid on endoplasmic reticulum (ER) stress and to detect the influence of tauroursodeoxycholic acid (TUDCA) on the expression of ER related genes in steatosis hepatocytes by establishing different models of hepatic steatosis.MethodsHealthy adult hepatocyte cell line HL-7702 was taken as research object.The model of hepatic steatosis was established with palmitic acid alone or mixed fatty acids.The cell viability was measured and calculated through CCK-8 positive cell proliferation assay.The cell morphology and steatosis was observed.The intracellular triglyceride content was tested with the triglyceride determination kit.With TUDCA intervention,the relative expression of Glucose-regulated protein 78 (GRP78) and CCAAT/Enhancer binding protein homologous protein (CHOP) at mRNA level was determined by real-time PCR.ResultsThe viability of hepatocyte was influenced once the concentration of mixed fatty acid reached 0.5 mmol/L or palmitic acid was 0.125 mmol/L.The effect of palmitic acid alone was stronger than that of mixed fatty acid on hepatocyte injury.The content of intra-hepatocyte triglyceride gradually increased in mixed fatty acid group,which only significantly increased after treated for 12 hours in palmitic acid alone group and then there was no significant change.There was no significant difference in relative expression of GRP78 and CHOP at mRNA level in various concentrations and treated time of mixed fatty acid group.After treated with palmitic acid at 0.5 mmol/L,intra-hepatocyte relative expression of CHOP at mRNA level increased obviously,however there was no effect on GRP78mRNA expression.After treated with palmitic acid at 1.0 mmol/L,both intra-hepatocyte GRP78 and CHOP mRNA relative expression increased.There was no significant difference in GRP78 and CHOP mRNA relative expression before and after ER stress in TUDCA intervented low dose palmitic acid group.There was significant difference in CHOP mRNA relative expression before and after ER stress in TUDCA intervented high dose palmitic acid group (at 12hrs:8.6400 to 5.1032; at 24hrs:13.7948to 6.4928,P=0.042 and 0.017),while no significant difference in GRP78 mRNA expression.ConclusionAt same fatty acid concentration,the larger propotion palmitic acid has,the more severe injury hepatocyte has.The regulation of palmitic acid on intra-hepatic ER stress is a time and dose dependent manner.TUDCA may improve palmitic acid induced ER stress to some degree.
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Objective To evaluate the relationship between fatty liver disease and liver metastases from colorectal cancer.Methods Eight hundred and ninety patients with colorectal cancer,who were submitted to hospital from 1993 to 2002 and had complete clinical data,were retrospectively analyzed.Of 890 patients,127 were diagnosed as fatty liver(FL)by ultrasonography,and the other 763 who were without fatty liver were served as controls(NFL).The clinical data including pathology,liver matastasis or mortality after surgery were analyzed.The survival rate and liver matastasis after surgery were followed up and statistically analyzed.Results The liver metastases was lower in FL group than that in NFL group(7 cases vs 102 cases,P=0.012).The tumor size was smaller in FL group than that in NFL group[(4.15±1.80)crn vs(4.77±2.25)cm,P=0.0016].The Dukes B(247/732,33.74%)and C(232/732,31.83%)patients were more common in NFL group,whereas Dukes A(41/121,33.61 %)and B(40/121,32.77%)were more common in FL group with significant difference(P＜0.05).No significant difference was found in 7-year survival rate between two groups who had been followed up(P=0.3024).Conclusion The lower incidence of liver metastases is found in FL group,which indicate that fatty liver disease may inhibit liver metastases from colorectal cancer by underlying mechanisms.
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<p><b>OBJECTIVE</b>To investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism.</p><p><b>METHODS</b>By establishing D-galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology.</p><p><b>RESULTS</b>There was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved.</p><p><b>CONCLUSIONS</b>Oxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.</p>
Subject(s)
Animals , Male , Rats , Alkaloids , Therapeutic Uses , Anti-Arrhythmia Agents , Therapeutic Uses , Calcium Hydroxide , Metabolism , Chemoprevention , Disease Models, Animal , Galactosamine , Liver Cirrhosis , Drug Therapy , Metabolism , Pathology , Liver Function Tests , Quinolizines , RNA, Messenger , Metabolism , Rats, Wistar , Superoxide Dismutase , Metabolism , Transforming Growth Factor beta , Genetics , MetabolismABSTRACT
Objective To evaluate the efficacy and safety of orlistat combined with low calorie diet in the treatment of obesity with non-alcoholic fatty liver disease. Methods Orlistat 120 mg, three times a day, combined with low calorie diet for a cause of 24 weeks, were given to the 60 non-alcoholic fatty liver disease (NAFLD) patients whose body mass index (BMI) were between 27 and 40. Results ①The percentage of mean weight loss and mean decreased BMI were both (10.76? 4.52 )% of their initinal weight at 24 weeks treatment. ②ALT, AST, GGT and total bilirubin was significantly decreased ( P
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Objective To establish the normal parameters of psychometric measures such as the number connection tests A(NCT-A)and digit symbol tests(DST)in assessment of minimal hepatic en- cephalopathy(MHE).Methods One hundred and sixty healthy volunteers(aged 25 to 64 years;educa- tional level＞9 years)were divided into＜35 ys,35～44 ys,45～54 ys and 55～64 ys groups.All of the healthy volunteers were assessed with NCT-A and DST to establish the normal value of age-related parameters,which can be used for diagnosis of MHE in patients with liver cirrhosis.Two standard devi- ation of the normal mean was used as a diagnostic criterion for MHE.One hundred and six cirrhotic patients were assessed with these parameters.Results The parameters of NCT-A were(25.1?4.6) sec in＜35 ys group,(32.1?6.8) sec in 35～44 ys group,(38.6?7.1)sec in 45～54 ys group or (49.3?6.3)sec in 55～64 ys group.The scores of DST were 49.9?4.7 in＜35 ys group,44.6?4.8 in 35～44 ys group,38.5?5.0 in 45～54 ys group or 35.4?4.7 in 55～64 ys group.Thirty one out of 106 cirrhotic patients were diagnosed as MHE based on these parameters.Conclusion The NCT- A and DST are psychometric assessments for diagnosis of MHE.Age-based normal paramerters of NCT- A and DST are needed to be established.
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Objective To investigate the prophylactic and therapeutic effect of oxymatrine(OM) on experimental liver fibrosis and to reveal its mechanism. Methods By establishing models of dimethylnitrosamine(DMN) induced liver fibrosis in rats, we observed the effect of oxymatrine on liver/weight index, serum and tissue biochemical indexes, content of liver hydroxyproline, expression of TGF?1 mRNA, electromicroscopic changes and tissue pathology. Results There was a decline of serum AST, ALT and liver hydroxyproline in oxymatrine group, compared to those of the DMN group( P
