Aim To observe the effects of cytokine signaling inhibition protein-3(SOCS3) on the liver fibrosis progression and reverse.Methods C57BL/6 mouse model was established by subcutaneous injection of carbon tetrachloride(CCl4).After a successful model of fibrosis, one-month normal diet was given to induce the reverse fibrosis model, while normal mice of the same gender and weight were as control group.Mice were sacrificed at 1, 2, 3, 4, 5, 6, 7, 8 weeks, respectively, then the liver tissue was harvested for the observation of its injury by hematoxylin and eosin(HE) staining.Then Masson staining was applied for the detection of changes in collagen, and the immunohistochemistry(IHC) for the observation of type Ⅰ Collagen(Colla-1), alpha smooth muscle actin(α-SMA), transforming growth factor beta 1(TGF-β1) and SOCS3 protein expression.In vitro formation of fibrosis was induced by TGF-β1 stimulating HSC-T6 cell lines, which was then reversed by MDI medium, with co-incubation of HSC-T6 cells with plasmid in the process of the reverse.Western blot was employed to detect SOCS3, Colla-1, α-SMA, TGF-β1 expression.Results The expression of SOCS3 and TGF-β1 increased in mouse model of fibrosis with the worsening fibrosis process and decreased in the reverse process.Over-expression SOCS3 in the reverse process reduced the development of liver fibrosis;meanwhile, the expression of TGF-β1 was also reduced accordingly.Conclusion SOCS3 may influence the development of the liver fibrosis and its reverse via regulating the expression of TGF-β1.

OBJECTIVETo investigate expression of the cysteinyl leukotriene receptor (CysLT1R) in hepatocellular carcinoma (HCC) tissues and determine its clinical significance.

METHODSCancerous and paraneoplastic liver tissues were collected from 30 patients with HCC and from 12 patients with liver hemangioma patients (controls). Real-time PCR and immunohistochemistry were used to evaluate the expression of CysLT1R in these tissues and assess the relationship with clinical pathological features. T-test,?Fisher's exact test and Kaplan-Meier survival analysis were used for statistical analysis.

RESULTSThe expression of CysLT1R in adjacent liver tissues (100%) was higher than that in the HCC (43.33%, P = 0.000) and normal liver tissues (41.67%, P = 0.000). The level of CysLT1R mRNA was also higher in paraneoplastic liver tissues (0.0339+/-0.0221) than in the paired HCC tissues (0.0127+/-0.0116, t = 2.911, P = 0.008) and normal liver tissues (0.0154+/-0.0123, t = -2.310, P = 0.033). There was no difference between the levels in HCC and normal liver tissues (P more than 0.05). Higher level of CysLT1R mRNA, higher level of serum alpha-fetoprotein, and higher tumor stage (III-IV) were associated with poor prognosis (respectively 4.372, P = 0.037; 24.187, P = 0.000; 8.75, P = 0.003). However, no evident relationship between the expression of CysLT1R and other clinical features was observed. Conclusions Overexpression of CysLT1R may contribute to the occurrence and progression of HCC.

Carcinoma, Hepatocellular ; diagnosis ; metabolism ; Case-Control Studies ; Disease Progression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Liver Neoplasms ; diagnosis ; metabolism ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Leukotriene ; metabolism ; alpha-Fetoproteins ; metabolism

Objective We sought to determine whether SF3a3 was capable of inhibiting HCV replication and to investigate the possible mechanisms.Methods Using the infectious HCV clones JFH1, we performed siRNA knockdown in Huh7.5.1 cells.First, we performed small interfering RNA (siRNA) to knock down SF3 gene expression.After 72 h incubation, Huh7.5.1 cells were infected with JFH1 for 24 h and then treated with 30IU/ml PEG-IFNα-2b for 48h.Members of SF3 family, HCV core and the key proteins of the IFN relative pathways were monitored by real time PCR and Western blot.Results SF3a3 mRNA level and protein expression were significantly decreased by SF3a3 specific siRNA compared with non-targeting siRNA, whose silencing effect was the best compared with other members of SF3a3 family;knockdown of SF3a3 protein expression by siRNA rescued HCV core expression, inhibited the role of interferon in anti-HCV infection under the same PEG-IFNα-2b pressure, and downregulated the phosphorylation of PI3K and Akt, as well as their total protein levels.Conclusions Silencing SF3a3 by specific siRNA could downregulate the expression of PI3K-Akt and p-PI3K/p-Akt proteins, which promoted the HCV replication.

OBJECTIVETo analyze the biochemical and pathological changes in mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet combined with low-dose streptozotocin (STZ) injections.

METHODSC57BL/6J mice were divided randomly into normal control group (NC group), high-fat diet group (HC group) and high-fat diet plus STZ group (HC+STZ group). The mice were fed on normal chow or a high-fat diet for 1 month before two introperitoneal injections of STZ (40 mg/kg) or citrate buffer with an interval of 24 h as appropriate. Fasting blood glucose (FBG) was detected every week for 4 weeks, and oral glucose tolerance test (OGTT) was performed one month after the injections, after which the biochemical profiles, islet and liver were evaluated by immunohistochemical and pathological analysis.

RESULTSIn HC+STZ group, FBG was above the cutoff value (13.89 mmol/L) in 75% of the mice at 1 week after STZ injections and in all the mice at two weeks except for the death of 1 mouse, with a success rate of modeling of 91.3%. FBG in HC group, though slightly higher than that in NC group, remained normal (6.8 mmol/L). The body weight in HC+STZ and HC groups was significantly higher than that in NC group after feeding but without obvious increases after the injections (P<0.01). Blood glucose in HC+STZ group at 0.5 to 2 h after OGTT and the area under curve (AUC) were higher than those in NC and HC groups (P<0.01); the AUC in HC group was a also higher than that in NC group (P<0.05). Plasma creatinine was significantly higher in HC+STZ group than in NC (P<0.01) and HC (P<0.05) groups. Insulin secretion by the islets decreased obviously in HC+STZ and HC group. The mice in HC+STZ group showed atrophy, fibrosis, and vacuolization in the islets with mild fatty liver but no visible renal pathologies.

CONCLUSIONHigh-fat diet and low-dose STZ injections can induce T2DM in mice with very similar biochemical and pathological changes to human T2DM and with such complications as fatty liver.

Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2 ; physiopathology ; Diet, High-Fat ; Fatty Liver ; physiopathology ; Glucose Tolerance Test ; Insulin ; Insulin Resistance ; Islets of Langerhans ; pathology ; Kidney ; pathology ; Mice ; Mice, Inbred C57BL ; Streptozocin

OBJECTIVE：To know about the co gnition level and self-medication behavior of antibiotics among urban and rural residents in Lu ’an city of Anhui province ，and to investigate its influential factors and to provide reference for promoting rational use of antibiotics. METHODS ：Totally 684 urban and rural residents aged 18-80 years in Lu ’an city were randomly selected as the research objects by stage sampling method. A self-designed questionnaire was used for household survey ，involving general demographic characteristics ，antibiotics related cognitive level ，antibiotics use behavior and related influential factors ，etc. RESULTS：A total of 657 questionnaires were collected ，with effective rate of 96.1％. Among them ，305 were from urban residents and 352 from rural residents. Among the 657 respondents，38.2％ were male and 61.8％ were female ；their age was （50.30±13.26）years old ；44.7％ of them were educated in primary school or below. 7.8％ of the respondents correctly recognized that antibiotics were not effective to the virus ；12.6％ knew antibiotic resistance ；55.1％ thought that frequent use of antibiotics would reduce the sensitivity of bacteria to it ；23.1％ said they knew the difference between prescription drugs and over-the-counter drugs；58.0％ could tell at least one case of not using antibiotics. For 7 knowledge items ，75.3％ of the residents in the survey area had a total score of less than 3；the cognition level of antibiotics was higher in urban areas and people with higher education level. 66.5％ of the respondents had used antibiotics in the past one year，of which 61.0％ obtained antibiotics by prescription 65161220。E-mail： from doctors ，50.7％ purchased antibiotics by themselves in pharmacies， and 13.1％ used the above two ways both. Among the people who have used antibiotics in the past year ， 81.9％ said they could buy antibiotics without prescription. Among the 657 respondents，49.0％ said that they had to obtain prescription from doctor when taking antibiotics ；68.9％ said that they would stop taking antibiotics when their symptoms improved；19.3％ would increase their dosage in order to enhance the curative effect ；28.3％ would change drugs frequently. Compared with urban residents ，rural residents were more likely to take antibiotics based on prescriptions by physicians [odds ratio （OR）＝1.693，95％ confidence interval （CI）（1.191，2.407）]. The higher the cognitive score ，the lower the behavior rate of having to prescribe antibiotics by doctors [OR ＝0.882，95％CI（0.785，0.991）]，and they were more likely to stop taking antibiotics when symptoms improved [OR ＝1.163，95％CI（1.025，1.319）]，and male were more inclined to increase the dosage of antibiotics to enhance the efficacy [OR ＝1.841，95％CI（1.214，2.792）]. The higher the cognitive score was ，the less likely they were to increase drug dosage to enhance the curative effect [OR ＝0.894，95％CI（0.773，1.034）]，nor were they inclined to change drugs frequently [OR ＝0.873，95％CI（0.767，0.992）]. CONCLUSIONS ：The cognition level to antibiotics of urban and rural residents in Lu ’an city needs to be improved urgently ，and reasonable antibiotic use behavior needs to be standardized. Pure knowledge of antibiotics is not necessarily related to the expected rational drug use behavior. Therefore ，in addition to health promotion for the rational use of drugs for residents ，it is also necessary to create a systematic environment that promotes the rational use of antibiotics and provide residents with multi-channel services for rational use of drugs.

AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats ; Animals ; Kainic Acid/toxicity* ; Brain-Derived Neurotrophic Factor/metabolism* ; Fibronectins/metabolism* ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Epilepsy/metabolism* ; Seizures/prevention & control*