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AIM:To investigate the effect of liraglutide ( LG) on the expression of fibronectin type Ⅲdomain-containing protein 5 (FNDC5) in the C2C12 myotubes.METHODS:The C2C12 mouse myoblast cell line was induced to differentiation.Differentiated cells were stimulated with gradient concentrations (1 ~1000 nmol/L) of LG for different time (0 ~24 h).The effects of LG on the expression of FNDC5 and the activation of adenosine 5'-monophosphate ( AMP)-activated protein kinase ( AMPK) signaling pathway were determined .After pretreated with glucagon-like peptide-1 ( GLP-1 ) receptor antagonist exendin 9-39 , the inhibitor of Ca 2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2), STO609, or the inhibitor of AMPK, Compound C, the LG-induced FNDC5 expression in C2C12 myotubes was examined.The expression of FNDC5 and the activation of AMPK were determined by Western blot .RESULTS: In C2C12 myotubes, LG promoted the expression of FNDC5 in a dose-and time-dependent manner .LG also activated AMPK signaling pathway .These effects of LG were partly abolished by exendin 9-39 , STO609 and Compound C .CONCLUSION:LG promotes the expression of FNDC5 via GLP-1 receptor in the C2C12 myotubes possibly through activation of the CAMKK2/AMPK signaling pathways .
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[ ABSTRACT] AIM:To investigate the role of hydrogen sulfide ( H2 S) on impaired wound healing in ob/ob mice and the underlying mechanism.METHODS:The ob/ob mice were randomly divided into 3 groups, including vehicle, in-sulin and NaHS for treatment.C57BL/6 mice were treated with vehicle as control.Full-thickness punch biopsy wounds were created on the mice.Firstly, H2 S concentrations in the skins and granulation tissues were measured.The mRNA ex-pression of cystathionineγ-lyase ( CSE) was detected by RT-qPCR.The protein expression of CSE and MMP-9 were deter-mined by Western blot.The neutrophil and monocyte/macrophage infiltration was analyzed by immunohistochemistry me-thod.The levels of tumor necrosis factor (TNF)-αand interleukin (IL)-6 were measured by ELISA.Collagen formation was measured by Masson staining.RESULTS:The H2 S levels in the skin and granulation were significantly decreased in ob/ob mice and increased in the NaHS-treated mice ( P to impaired wound healing in diabetes, which is alleviated by exogenous H2 S possibly through anti-inflammation.
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AIM:To investigate the effect of hydrogen sulfide ( H2 S) on high glucose ( HG)-induced injury of the mouse podocyte cell line MPC5.METHODS: The cultured MPC5 cells were randomly divided into 4 groups: HG group, normal glucose (NG) group, NG+DL-propargylglycine (PPG) group, and HG+NaHS group.After treated for a certain time, the cells were collected for further detection .The expression of zonula occludens-2 (ZO-2), nephrin,β-cate-nin and cystathionine γ-lyase ( CSE) was determined by Western blotting .RESULTS:High glucose significantly reduced the expression of nephrin, ZO-2 and CSE (P<0.05), while the level of β-catenin was elevated obviously (P<0.05), all in a time-dependent manner.NG+PPG inhibited the levels of ZO-2 and nephrin significantly (P<0.05), and increased the level of β-catenin (P<0.05), all in a PPG concentration-dependent manner.HG+NaHS induced a more significant increase in the levels of ZO-2 and nephrin as compared with HG group (P<0.01), whereas a severe reduction of β-cate-nin in HG+NaHS group was observed as compared with HG group .Compared with NG group , the expression of ZO-2 and nephrin was decreased obviously , and the level of β-catenin was increased in HG +NaHS group.CONCLUSION:Down-regulation of CSE contributes to hyperglycemia-induced podocyte injury .Exogenous H 2 S protects against hyperglycemia-in-duced podocyte injury , possibly through up-regulation of ZO-2 and subsequent suppression of Wnt/β-catenin pathway .
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Objective To explore the relationship between serum cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP),tumor necrosis factor-alpha (TNF-α ) in patients with acute organophosphorus pesticide poisoning (AOPP) and their clinical significance.Methods One hundred and twelve patients with AOPP (without sudden death ) were as AOPP group.One hundred and twelve healthy controls were as control group.Serum cTnI,hs-CRP and TNF-α levels were determined by ELISA and compared between two groups.The relationship between serum cTnI and hs-CRP,TNF-α was analyzed.Time for atropinization and acetylcholinesterase activity recovery and days of hospitalization were observed.The effectiveness of AOPP patients in different serum cTnI levels was compared.Results Serum cTnI,hs-CRP and TNF- α levels in AOPP group[0.75 (0.26,0.99) μ g/L,11.57(5.13,21.62) mg/L,( 12.36 ±5.22) μ g/L] were higher than those in control group[0.01 (0,0.03) μ g/L,3.62(2.31,6.80) mg/L,(7.33 ±4.31 ) μ g/L] (P ＜ 0.01 ).Serum cTnI levels were positive correlation with serum hs-CRP and TNF- α levels in AOPP patients (r =0.53,0.62,P ＜ 0.01 ).Time for atropinization and acetylcholinesterase activity recovery and days of hospitalization in higher serum cTnI levels patients ( 56 cases ) [(7.31 ± 1.96),( 15.29 ± 3.66 ),(17.23 ± 3.62) d] was longer than that in lower serum cTnI levels patients (56 cases)[(5.32 ± 1.03),( 11.32 ± 2.59),( 13.66 ± 3.03) d](P＜ 0.01).Conclusions Cardiac insults in AOPP patients are related to inflammation.Sudden death-free AOPP patients with higher cTnI levels have less response to treatments.
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Objective To examine the correlation of imbalance of urinary exosome Th1/Th2 with diabetic nephropathy (DN).Methods A total of 120 patients with type 2 diabetes mellitus (DM) and 30 healthy volunteers as control were enrolled in the study.According to urinary albumin/creatinine ratio (UACR),type 2 diabetes mellitus patients were divided into 3 groups:diabetes mellitus without nepbropathy group (DM,n=40,UACR＜30 mg/gCr),microalbuminuria group (DN 1,n=50,UACR-30～300 mg/gCr) and clinicoalbuminuria group (DN 2,n=30,UACR＞300 mg/gCr).Urine exosome-interferon-gamma (IFN-γ) and exosome-interleukin 4 (IL-4) levels were determined by enzyme-linked immunosorbent assay (ELISA).Multiple stepwise linear regression was used to analyze the correlation of exosome-IFN-γ/IL-4 with glycated hemoglobin (HbA1c),cholesterol (CH),UACR,Scr and BUN.Results Th1/Th2 ratio in DM,DN1,DN2 groups was significantly higher than that in healthy group (0.8089±0.2458,0.8993 ±0.3515,0.8571±0.2470 vs 0.6198±0.1769,all P＜0.01).Correlation analysis showed that urinary exosomeIFN-γ/IL-4 ratio was positively correlated with UACR (r=0.213,P=0.015) and BUN (r=0.292,P=0.001).Multiple stepwise linear regression analysis showed that BUN was independent determinants for exosome-IFN-γ/IL-4 (β=0.246,P=0.006).Conclusion The imbalance of urinary exosomeTh1/Th2 is correlated with DN,which may play an important role in the pathogenesis of DN.
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Objective: Chlamydia pneumoniae is a kind of common pathogenic bacteria in respiratory passage which cause persistent and chronic infection cell mediated immunity results mainly followiny the infection.The infection kinetics and local in vitro-restimulated cell mediated immunity(CMI) responses in the lungs and spleens of Icr mice during Chlamydia pneumoniae(Cpn) primary infection and reinfection will be analyzed in this article.Methods: Icr mice were inoculated intranasally with 105 IFU of Cpn(PT group).The same dose was given in the same way as rechallenge 4 weeks after the primary challenge(ST group).Control groups were inoculated with 0.05 ml PBS.The mice were sacrificed at predetermined days,and the pulmonary mononuclear cells and splenic lymphocytes were isolated and stimulated with Cpn in vitro for 3 days.The proliferative response was measured by MTT;IL-4,IL-10 and IFN-? were detected by ELISA.Results: The PT group showed a weak proliferative response and no secretion of IFN-? in the lungs after Cpn stimulation,while the ST group presented a reinfection characterized by IFN-? production both in the lungs and in the spleens(P