Curcumin protects against acetaminophen-induced apoptosis in hepatic injury

AIM:To explore the effects of curcumin(CMN)on hepatic injury induced by acetaminophen(APAP)in vivo.METHODS:Male mice were randomly divided into three groups:groupⅠ(control)mice received the equivalent volumes of phosphate-buffered saline(PBS)intraperitoneally(ip);GroupⅡ[APAP+carboxymethylcellulose(CMC)]mice received 1%CMC(vehicle)2h before APAP injection;GroupⅢ(APAP+CMN)mice received curcumin(10 or 20 mg/kg,ip)2 h before before or after APAP challenge.In GroupsⅡandⅢ,APAP was dissolved in pyrogen-free PBS and injected at a single dose of 300 mg/kg.CMN was dissolved in 1%CMC.Mice were sacrificed 16 h after the APAP injection to determine alanine aminotransferase(ALT)levels in serum and malondialdehyde(MDA)accumulation,superoxide dismutase(SOD)activity and hepatocyte apoptosis in liver tissues.RESULTS:Both pre-and post-treatment with curcumin resulted in a significant decrease in serum ALT compared with APAP treatment group(10 mg/kg:801.46±661.34 U/L;20 mg/kg:99.68±86.48 U/L vs 5406.80±1785.75 U/L,P<0.001,respectively).The incidence of liver necrosis was significantly lowered in CMN treated animals.MDA contents were significantly reduced in 20 mg/kg CMN pretreatment group,but increased in APAP treated group(10.96±0.87 nmol/mg protein vs 16.03±2.58 nmol/mg protein,P<0.05).The decrease of SOD activity in APAP treatment group and the increase of SOD in 20 mg/kg CMN pretreatment group were also detected(24.54±4.95 U/mg protein vs 50.21±1.93 U/mg protein,P<0.05).Furthermore,CMN treatment efficiently protected against APAPinduced apoptosis via increasing Bcl-2/Bax ratio.CONCLUSION:CMN has significant therapeutic potential in both APAP-induced hepatotoxicity and other types of liver diseases.     

Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice

AIM: To investigate the hepatic protective effects of 5-methoxypsoralen (5-MOP) and to learn if 5-MOP causes hepatotoxicity at protective doses.METHODS: C57BL/6J mice were administrated orally with 5-MOP at doses of 12.5, 25 and 50 mg/kg body weight respectively every morning for 4 d before given acetaminophen (APAP) subcutaneously at a dose of 500 mg/kg. The 5-MOP alone group was treated with 5-MOP orally at a dose of 50 mg/kg body weight for 4 d without APAP. Twenty-four hours after APAP administration, blood samples of mice were analyzed for serum enzyme alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) levels, and malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG) of liver tissues were measured and histopathologic changes of the liver were observed.RESULTS: Compared with the vehicle control group, the serum levels (IU/L) of ALT, AST and LDH were all increased significantly in APAP group (8355 ± 3940 vs 30 ± 21, P < 0.05; 6482 ± 4018 vs 146 ± 58, P < 0.05; 24627 ± 10975 vs 1504 ± 410, P < 0.05). Compared with APAP group, the serum ALT levels (IU/L) (1674 ± 1810 vs 8355 ± 3940, P < 0.05; 54 ± 39 vs 8355 ± 3940, P < 0.05; 19 ± 9 vs 8355 ± 3940, P < 0.05), AST levels (IU/L) (729 ± 685 vs 6482 ± 4108, P < 0.05; 187 ± 149 vs 6482 ± 4108, P < 0.05; 141 ± 12 vs 6482 ± 4108, P < 0.05) and LDH levels (IU/L) (7220 ± 6317 vs 24 627 ± 10 975, P < 0.05; 1618 ± 719 vs 24 627 ± 10 975, P < 0.05; 1394 ± 469 vs 24 627 ± 10 975, P < 0.05) were all decreased drastically in the three-dosage 5-MOP pretreatment groups. Pretreatment of 5-MOP could attenuate histopathologic changes induced by APAP, including hepatocellular necrosis and infiltration of inflammatory cells, and the effect was dose-dependent. MDA levels (nmol/mg) were decreased by 5-MOP in a dose-dependent manner (0.98 ± 0.45 vs 2.15 ± 1.07, P > 0.05; 0.59 ± 0.07 vs 2.15 ± 1.07, P < 0.05; 0.47 ± 0.06 vs 2.15 ± 1.07, P < 0.05). The pretreatment of 5-MOP could also increase the GSH/GSSG ratio (3.834 ± 0.340 vs 3.306 ± 0.282, P > 0.05; 5.330 ± 0.421 vs 3.306 ± 0.282, P < 0.05; 6.180 ± 0.212 vs 3.306 ± 0.282, P < 0.05). In the group treated with 5-MOP but without APAP, the serum enzyme levels, the liver histopathologic manifestation, and the values of MDA and GSH/GSSG ratio were all normal.CONCLUSION: 5-MOP can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity and possesses an antioxidative activity, and does not cause liver injury at the protective doses.     

Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats

AIM: To investigate the role of the hydrogen-rich water(HRW) in the prevention of aspirin-induced gastric mucosal injury in rats. METHODS: Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde(MDA), superoxide dismutase(SOD), myeloperoxidase(MPO), interleukin(IL)-06 and tumor necrosis factor(TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2(COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively. RESULTS: Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores(4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group(2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues(37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues(46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum(505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues(staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05). CONCLUSION: HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues.     

Regulatory effect and mechanisms of carbon monoxidereleasing molecule Ⅱ on hepatic energy metabolism in septic mice

AIM:To investigate the possible mechanisms of exogenous carbon monoxide-releasing moleculeⅡ(CORM-2)intervention on hepatic energy metabolism in experimental sepsis.METHODS:Forty-eight C57BL/6 mice were randomly divided into four groups(n=12):sham group;cecal ligation and puncture(CLP)group;CLP+CORM-2group and CLP+iCORM-2(inactive CORM-2)group.Survival rates were determined after 72 h.Twenty-four similarly treated mice(n=6 in each group)were assayed for post-operative continuous blood glucose in the first 36 h.Thirty-six similarly treated mice(n=9in each group)underwent micro-positron emission tomography(PET)scanning after tail vein injection of18Ffluorodeoxyglucose(FDG)24 h after operation.Plasma and liver specimens were collected for assay of liver pathology,alanine transaminase(ALT)and aspartate transaminase(AST)activities.Hepatic glucokinase activity,lactic acid levels and mitochondrial swelling were also determined.RESULTS:Improved survival was observed in CORM-2treated mice.Both the CLP and CLP+CORM-2 groups had sustained low blood glucose levels within the first post-operative 36 h.18F-FDG micro-PET images showed abnormally high levels of hepatic glucose metabolism(standardized uptake value)in the CLP group(2.76±0.39 vs 0.84±0.14,P<0.01),which declined to normal levels after CORM-2 intervention(1.29±0.32 vs2.76±0.39,P<0.05).glucokinase activity was markedly increased in the CLP group(6.38±0.56 U/g vs 4.60±0.21 U/g,P<0.01),but was normal after CORM-2intervention(4.74±0.14 U/g vs 6.38±0.56 U/g,P<0.05).CORM-2 suppressed plasma lactic acid levels(4.02±0.02 mmol/L vs 7.72±2.37 mmol/L,P<0.05)and protected hepatic mitochondria in CLP mice.CORM-2 intervention also reduced elevated plasma AST(199.67±11.08 U/L vs 379.67±16.34 U/L,P<0.05)and ALT(63.67±12.23 U/L vs 112.67±9.74 U/L,P<0.05)activities in CLP mice.CONCLUSION:The release of CO molecules by CORM-2 protects mitochondria and maintains a stable level of hepatic glucose metabolism.Thus,CORM-2 improves liver function and survival in septic mice.     

I_κB kinase-beta inhibitor attenuates hepatic fibrosis in mice

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice rec...     

Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats

AIM:To evaluate the ameliorative effect of naringenin(NG)during ulcerative colitis(UC)in rats.METHODS:Rats were treated with three different doses(25,50 and 100 mg/kg per day)of NG and a single dose of mesalazine(MES,300 mg/kg per day)for seven days prior to ulcerative colitis induction by4%acetic acid(AA).Twenty four hours after AA rectal administration,animals were scarified and the colonic tissues were dissected.Colonic mucus content was estimated using Alcian blue dye binding technique.In colon tissues,levels of total glutathione sulphadryls(T-GSH),non-protein sulphadryls(NP-SH)and thiobarbituric acid reactive substances(TBARS)were evaluated.The activities of the antioxidant enzymes,catalase(CAT)and superoxide dismutase(SOD)were measured.Concentrations of nucleic acids(DNA and RNA)and total protein were also estimated in colon tissues.Colonic levels of tumor necrosis factor-(TNF-),interleukin-1(IL-1),interleukin-6(IL-6),prostaglandin E2(PGE2)and nitric oxide(NO)were estimated.In cross section of colitis tissue the histopathological changes were observed.RESULTS:Colonic mucus content was decreased in AA compared to controls(587.09±65.59 mg/kg vs941.78±68.41 mg/kg,P<0.001).AA administration markedly reduced T-GSH(5.25±0.37 nmol/L vs 3.04±0.24 nmol/L,P<0.01),NP-SH(3.16±0.04 nmol/L vs 2.16±0.30 nmol/L,P<0.01),CAT(6.77±0.40 U/mg vs 3.04±0.2 U/mg,P<0.01)and SOD(3.10±0.11U/mg vs 1.77±0.18 U/mg,P<0.01)while TBARS,TNF-,IL-1,IL-6,PGE2 and NO levels(15.09±3.84nmol/L vs 59.90±16.34 nmol/L,P<0.01;113.56±1.91 pg/mg vs 134.24±4.77 pg/mg,P<0.01;209.20±36.38 pg/mg vs 422.19±31.47 pg/mg,P<0.01;250.83±25.09 pg/mg vs 638.58±115.9 pg/mg,P<0.01;248.19±36.98 pg/mg vs 541.74±58.34 pg/mg,P<0.01 and 81.26±2.98 mmol/g vs 101.90±10.73 mmol/g,P<0.001)were increased in colon of rats with UC compared controls respectively.Naringenin supplementation,significantly and dose dependently increased the colonic mucus content.The elevated TBARS levels were significantly decreased(39.35±5.86n     

Effects of tetrandrine on gastric mucosa and liver in portal hypertensive rats

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Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM:To investigate the protective effects of ethyl pyruvate(EP) on acute-on-chronic liver failure(ACLF) in rats.METHODS:An ACLF model was established in rats,and animals were randomly divided into normal,model and EP treatment groups.The rats in EP treatment group received EP(40 mg/kg) at 3 h,6 h,12 h and 24 h after induction of ACLF.Serum endotoxin,high mobility group box-1(HMGB1),alanine transaminase(ALT),tumor necrosis factor-(TNF-),interferon-(IFN-),interleukin(IL)-10 and IL-18 levels,changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF.The effects of EP on the survival of ACLF rats were also observed.RESULTS:Serum levels of endotoxin(0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL,P 0.001),HMGB1(35.42 ± 10.86 g/L vs 2.14 ± 0.27 g/L,P 0.001),ALT(8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L,P 0.001),TNF-(190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L,P 0.001),IFN-(715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L,P 0.001),IL-10(6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L,P 0.001) and IL-18(85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L,P 0.001) were significantly increased,and liver tissues presented severe pathological injury in the model group compared with the normal group.However,EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin(0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL,P 0.001) and inflammatory cytokines(11.13 ± 2.58 g/L vs 35.42 ± 10.86 g/L for HMGB1,3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT,128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-,438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-,3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10,and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18,respectively,P 0.001),and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF.EP treatment at the four time points prolonged the median survival time of ACLF rats(60 h) to 162 h,120 h,102 h and 78 h,respectively(2 = 41.17,P 0.0001).CONCLUSION:EP administration can protect against ACLF in rats,and is a potential and novel therapeutic agent for severe liver injury.     

Intestinal dendritic cells change in number in fulminant hepatic failure

AIM:To investigate the change in intestinal dendritic cell(DC)number in fulminant hepatic failure(FHF).METHODS:An animal model of FHF was created.Intestinal CD11b/c was detected by immunohistochemistry and Western blot.Quantitative real-time polymerase chain reaction(PCR)was used to detect intestinal integrin-αm RNA expression.Intestinal CD83,CD86,CD74,CD3 and AKT were detected by immunohistochemistry,Western blot and PCR.Phosphorylated-AKT(p-AKT)was detected by immunohistochemistry and Western blot.RESULTS:In the FHF group[D-galactosamine(D-Galn)+lipopolysaccharide(LPS)group],the mice began to die after 6 h;conversely,in the D-Galn and LPS groups,the activity of mice was poor,but there were no deaths.Immunohistochemistry results showed that in FHF,the expression of CD11b/c(7988400±385941vs 1102400±132273,P0.05),CD83(13875000±467493 vs 9257600±400364,P0.05),CD86(7988400±385941 vs 1102400±13227,P0.05)and CD74(11056000±431427 vs 4633400±267903,P0.05)was significantly increased compared with the normal saline(NS)group.Compared with the NS group,the protein expression of CD11b/c(5.4817±0.77 vs 1.4073±0.37,P0.05)and CD86(4.2673±0.69 vs 1.1379±0.42,P0.05)was significantly increased.Itg-α(1.1224±0.3 vs 0.4907±0.19,P0.05),CD83(3.6986±0.40 vs 1.0762±0.22,P0.05)and CD86(1.5801±0.32 vs 0.8846±0.10,P0.05)m RNA expression was increased significantly in the FHF group.At the protein level,expression of CD74in the FHF group(2.3513±0.52)was significantly increased compared with the NS group(1.1298±0.33),whereas in the LPS group(2.3891±0.47),the level of CD74 was the highest(P0.05).At the gene level,the relative expression of CD74 m RNA in the FHF group(1.5383±0.26)was also significantly increased in comparison to the NS group(0.7648±0.22;P0.05).CD3 expression was the highest in the FHF group(P0.05).In the FHF,LPS and D-Galn groups,the expression of AKT at the protein and m RNA levels was elevated compared with the NS group,but there wasno statistical significance(P0.05).The p-AKT protein expression in the FHF(1.54±0.06),LPS(1.56±0.05)and D-Galn(1.29±0.03)groups was higher than that in the NS group(1.07±0.03)(P0.05).CONCLUSION:In FHF,a large number of DCs mature,express CD86,and activate MHC classⅡmolecular pathways to induce a T cell response,and the AKT pathway is activated.     

Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice

AIM:To investigate the effects of Lactobacillus plantarum(L.plantarum) CAI6 and L.plantarum SC4 on hyperlipidemic mice.METHODS:Male Kunming mice were fed a highcholesterol diet for 28 d to construct hyperlipidemic models.Hyperlipidemic mice and normal mice were assigned to 3 groups which were separately treated with L.plantarum CAI6,L.plantarum SC4,and physiological saline through oral gavage for 28 d.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C) levels were measured by commercially available enzyme kits.FACS Calibur flow cytometry was used to examine hepatic and renal nuclear factor-erythroid 2-related factor 2(Nrf2) expression.The morphology of livers was checked by hematoxylin and eosin staining and optical microscope observation.RESULTS:Compared with normal mice,hyperlipidemic mice possessed significantly higher TC(3.50 ± 0.43 vs 2.89 ± 0.36,P < 0.01),TG(1.76 ± 0.07 vs 1.10 ± 0.16,P < 0.01),and LDL-C(1.72 ± 0.20 vs 0.82 ± 0.10,P < 0.01) levels,resulting in an increase of atherogenic index(AI)(2.34 ± 1.60 vs 0.93 ± 0.55,P < 0.05) and LDL-C/HDL-C ratio(1.43 ± 0.12 vs 0.51 ± 0.16,P < 0.05).After treatment with L.plantarum CAI6/L.plantarum SC4,TG(1.43 ± 0.27/1.54 ± 0.10 vs 1.76 ± 0.07,P < 0.01/P < 0.05) and LDL-C(1.42 ± 0.07/1.47 ± 0.12 vs 1.72 ± 0.20,P < 0.01/P < 0.01) in hyperlipidemic mice significantly decreased.In addition,TC,HDL-C,AI,and LDL-C/HDL-C ratio were all positively changed.Meanwhile,the treatment markedly alleviated hepatic steatosis and significantly stimulated Nrf2 expression(73.79 ± 0.80/72.96 ± 1.22 vs 54.94 ± 1.84,P < 0.01/P < 0.01) in hepatocytes of hyperlipidemic mice.CONCLUSION:L.plantarum CAI6 and L.plantarum SC4 may protect against cardiovascular disease by lipid metabolism regulation and Nrf2-induced antioxidative defense in hyperlipidemic mice.     

Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis

AIM： To investigate the correlation between the antifibrotic effect of baicalin and serum cytokine production in rat hepatic fibrosis, METHODS： Forty male Sprague-Dawley rats were divided randomly into four groups： normal control group, model group, baicalin-treated group, and colchicine-treated group. Except for the normal control group, all rats in the other groups were administered with carbon tetrachloride to induce hepatic fibrosis. At the same time, the last two groups were also treated with baicalin or colchicine. At the end of the 8 wk, all animals were sacrificed. Serum alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）, transforming growth factor （TGF）-β1, tumor necrosis factor （TNF）-α, interleukin （IL）-6 and IL-10 were measured. Liver index, hepatic hydroxyproline content and the degree of liver fibrosis were also evaluated. RESULTS： The levels of ALT, AST and liver index in the baicalin-treated group were markedly lower than those in the model group （ALT： 143.88 ± 14.55 U/L vs 193.58± 24.35 U/L; AST： 263.66 ± 44.23 U/L vs 404.37± 68.29 U/L; liver index： 0.033 ± 0.005 vs 0.049± 0.009, P 〈 0.01）. Baicalin therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percentage in liver tissue （P 〈 0.01）. Furthermore, the levels of serum TGF-β1, TNF-α and IL-6 were strikingly reduced in the baicalin-treated group compared with the model group, while the production of IL-10 was up-regulated： （TGF-β1：260.21 ± 31.01 pg/mL vs 375.49 ± 57.47 pg/mL; TNF-α： 193.40±15.18 pg/mL vs 260.04 ± 37.70 pg/mL; IL-α：339.87 ± 72.95 pg/mL vs 606.47 ± 130.73 pg/mL; IL-10：506.22 ± 112.07 pg/mL vs 316.95 ± 62.74 pg/mL, P 〈 0.01）. CONCLUSION： Baicalin shows certain therapeutic effects on hepatic fibrosis, probably by immunoregulating the imbalance between profibrotic and antifibrotic cytokines.     

Overexpressed miRNA-155 dysregulates intestinal epithelial apical junctional complex in severe acute pancreatitis

AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for mi     

Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers

AIM:To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor(CFBB)based on microencapsulated immortalized human hepatocytes.METHODS:Encapsulated hepatocytes were placed in the constructed CFBB and circulated through Dulbecco’s Modified Eagle’s Medium(DMEM)for 12 h,and then through exchanged plasma for 6 h,and compared with encapsulated cells cultivated under static conditions in a spinner flask.Levels of alanine aminotransferase(ALT)and albumin were used to evaluate the CFBB during media circulation,whereas levels of ALT,total bilirubin(TBil),and albumin were used to evaluate it during plasma circulation.Mass transfer and hepatocyte injury were evaluated by comparing the results from the two experimental conditions.In addition,the viability and microstructure of encapsulated cells were observed in the different environments.RESULTS:The bioartificial liver model based on a CFBB was verified by in vitro experiments.The viability of encapsulated cells accounting for 84.6%±3.7%in CFBB plasma perfusion was higher than the 74.8%±3.1%in the static culture group(P<0.05)after 6 h.ALT release from cells was 29±3.5 U/L vs 40.6±3.2U/L at 12 h(P<0.01)in the CFBB medium circulation and static medium culture groups,respectively.Albumin secretion from cells was 234.2±27.8μg/1×107cells vs 167.8±29.3μg/1×107 cells at 6 h(P<0.01),274.4±34.6μg/1×107 cells vs 208.4±49.3μg/1×107 cells(P<0.05)at 12 h,in the two medium circulation/culture groups,respectively.Furthermore,ALT and TBil levels were 172.3±24.1 U/L vs 236.3±21.5 U/L(P<0.05),240.1±23.9μmol/L vs 241.9±31.4μmol/L(P>0.05)at 6 h in the CFBB plasma perfusion and static plasma culture groups,respectively.There was no significant difference in albumin concentration between the two experimental plasma groups at any time point.The microstructure of the encapsulated hepatocytes remained healthier in the CFBB group compared with the static culture group after 6 h of plasma perfusion.CONCLUSION:The CFBB can function as a bioartificial liver based on a bioreactor.The efficacy of this novel bioreactor is promising for the study of liver failure.     

Yi-Qi-Zeng-Min-Tang, a Chinese medicine, ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabe...     

Biliary fistula after treatment for hydatid disease of the liver:When to intervene

AIM:To determine the outcome of patients with biliary fistula(BF)after treatment for hydatid disease of the liver. METHODS:Between January 2000 and December 2010,out of 301 patients with a diagnosis of hydatid cyst of the liver,282 patients who underwent treatment [either surgery or puncture,aspiration,injection and reaspiration(PAIR)procedure]were analysed.Patients were grouped according to the presence or absence of postoperative biliary fistula(PBF)(PBF vs no-PBF groups,respectively).Preoperative clinical,radiological and laboratory characteristics,operative characteristics including type of surgery,peroperative detection of BF,postoperative drain output,morbidity,mortality and length of hospital stays of patients were compared amongst groups.Multivariate analysis was performed to detect factors predictive of PBF.Receiver operative characteristics(ROC)curve analysis were used to determine ideal cutoff values for those variables found to be significant.A comparison was also made between patients whose fistula closed spontaneously(CS)and those with intervention in order to find predictive fac-tors associated with spontaneous closure. RESULTS:Among 282 patients[median(range)age, 23(16-78)years;77.0%male];210(74.5%)were treated with conservative surgery,33(11.7%)radical surgery and 39(13.8%)underwent percutaneous drainage with PAIR procedure A PBF developed in 46(16.3%) patients,all within 5 d after operation.The maximum cyst diameter and preoperative alkaline phosphatase levels(U/L)were significantly higher in the PBF group than in the no-PBF group[10.5±3.7 U/L vs 8.4±3.5 U/L(P<0.001)and 40.0±235.1 U/Lvs 190.0±167.3 U/L(P=0.02),respectively].Hospitalization time was also significantly longer in the PBF group than in the no-PBF group[37.4±18.0 d vs 22.4±17.9 d(P< 0.001)].A preoperative high alanine aminotransferase level(>40 U/L)and a peroperative attempt for fistula closure were significant predictors of PBF development (P=0.02,95%CI:-0.03-0.5 and P=0.001,95%CI:0.1-0.4),respectively.Comparison of     

Effect of Lianshu preparation on lipopolysaccharide-induced diarrhea in rats

AIM： To investigate the effect of Lianshu preparation on lipopolysaccharide （LPS）-induced diarrhea in rats. METHODS： A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS ＋ Lianshu group, LPS ＋ berberine group （n = 10 in each group）. Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na^＋, K^＋, Cl and hematocrit, plasma nitrogen monoxide （NO）, diamine oxidase （DAO）, and D （-）-lactate were measured. The number of IgA＋ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer＇s yeast-induced pyrexia （10 mL/kg of 20% aqueous suspension）. Acetaminophen （250 mg/kg, intragastric administration, bid） was comparison. Temperature used as a standard drug for was recorded 1 h before and 6 h after Brewer＇s yeast injection. Finally, small intestina transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin （2 mg/kg）. Atropine （10 g/kg） was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS： The frequency of diarrhea was higher in LPS group than in LPS ＋ Lianshu group and LPS ＋ berberine group （36.70± 5.23 vs 28.50 ±4.06 and 32.70±9.30 respectively, P 〈 0.01）, and lower in LP5 ＋ Lianshu group than in LPS ＋ berberine group （P = 0.03）. The levels of Na＋, glucose, Cl, K^＋ were significantly lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （140.35±3.19 mmol/L vs 131.99±4.86 mmol/L, 8.49 ±1.84 mmol/L vs 6.54±2.30 mmol/L, 106.29± 4.41 mmol/L vs 102.5±1.39 mmol/L, 5.08±0.66 mmol/L vs 4.32 ± 0.62 mmol/L respectively, P 〈 0.05）. The level of hematocrit was lower in LPS ＋ Lianshu group than in LPS ＋ berberine group （0.50% ±0.07% vs 0.59%± 0.10% respectively, P 〈 0.05）. The plasma levels of NO, DAO and D （-）-lactate were higher in LPS group than in normal group （79.74 ± 7.39μmol/L vs 24.94 ± 3.38μmol/L, 2.48 ±0.42μ/mL vs 0.82 ±0.33 p/mL, 5.63± 0.85μg/mL vs 2.01 ±0.32 μg/mL respectively, P 〈 0.01）, and lower in LPS ＋ Lianshu group than in LP5 ＋ berberine group （48.59±4.70μmol/L vs 51.56 ±8.38 μmol/L, 1.43± 0.53μmol/mL vs 1.81 ±0.42 μmol/mL, 4.00± 0.54 μg/mL vs 4.88 ± 0.77 pg/mL respectively, P 〈 0.05）. The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS ＋ Lianshu group than in LPS group. The number of IgA＋ plasma cells and amount of SIgA were higher in LPS ＋ Lianshu group than in LPS group （1.16±0.19/μm^2 vs 1.09±0.28/μm^2, P = 0.026; 0.59 ±0.12 mg/L vs 0.15± 0.19 mg/L respectively, P = 0.000）. Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION： Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.     

Investigation of genome instability in patients with non-alcoholic steatohepatitis

AIM:To evaluate the occurrence of micronucleus(MN),nucleoplasmic bridges(NPBs)and nuclear buds(NBUDs)in the mitogen-stimulated lymphocytes of patients with non-alcoholic steatohepatitis(NASH).METHODS:The study was performed in 25(9 females,16 males)patients newly diagnosed with NASH,and 25healthy subjects of similar ages and genders were used as a control group.None of the controls was known to be receiving any drugs for medical or other reasons or using alcohol.Hepatosteatosis was further excluded by abdominal ultrasound imaging in the control group.The numbers of MN,NPBs and NBUDs scored in binucleated(BN)cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects.Statistical comparisons of the numbers of BN cells with MN,NPBs and NBUDs and ages between the patients with NASH and control subjects were performed.RESULTS:The mean ages of the patients and the control group were 41.92±13.33 and 41.80±13.09 years(P>0.05),respectively.The values of the mean body mass index(BMI),HOMA-IR,hemoglobin,creatinin,aspartate aminotransferase,alanine aminotransferase,triglyceride,high density lipoprotein,and low density lipoprotein were 31.19±4.62 kg/m2vs 25.07±4.14 kg/m2,6.71±4.68 vs 1.40±0.53,14.73±1.49 g/dL vs 14.64±1.30 g/dL,0.74±0.15 mg/dL vs 0.80±0.13 mg/dL,56.08±29.11 U/L vs 16.88±3.33 U/L,92.2±41.43U/L vs 15.88±5.88 U/L,219.21±141.68 mg/dL vs102.56±57.98 mg/dL,16.37±9.65 mg/dL vs 48.72±15.31 mg/dL,and 136.75±30.14 mg/dL vs 114.63±34.13 mg/dL in the patients and control groups,respectively.The total numbers and frequencies of BN cells with MN,NPBs and NBUDs,which were scored using the CBMN cytome assay on PHA-stimulated lymphocytes,were evaluated in the patients with NASH and control group.We found significantly higher numbers of MN,NPBs and NBUDs in the BN cells of patients with NASH than in those of the control subjects(21.60±9.32vs 6.88±3.91;29.28±13.31 vs 7.84±3.96;15.60±5.55 vs 4.20±1.63,respectively,P<0.0001).CONCLUSION:The increased numbers of MN,N     

Association of chronic viral hepatitis B with insulin resistance

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P 0.001),waist circumference(r =0.356,P 0.001),percent body fat(r = 0.296,P 0.001),systolic blood pressure(r = 0.202,P 0.001),total cholesterol(r = 0.134,P 0.001),triglycerides(r = 0.292,P 0.001),cystatin C(r = 0.069,P 0.001) and uric acid(r = 0.142,P 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P 0.001),waist circumference(r = 0-0.243,P 0.001),percent body fat(r =-0.217,P 0.001),systolic blood pressure(r =-0.132,P 0.001),total cholesterol(r =-0.106,P 0.001),triglycerides(r =-0.205,P 0.001),cystatin C(r =-0.044,P 0.001) and uric acid(r =-0.096,P 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.