Pharmaceutical inactivation of Erk1/2 does not affect function of FGF21 to regulate glucose and lipid metabolic hemostasis / 中国病理生理杂志

AIM: To investigate whether inactivation of extracellular signal-regulated kinase 1/2 ( Erk1/2 ) will affect the function of fibroblast growth factor 21 (FGF21) to regulate glucose and lipid metabolism .METHODS:Male db/db mice (8 weeks old) were treated with U0126 (an inhibitor of Erk1/2 kinase) for 1 week, and then treated with re-combinant human FGF21 protein and adenovirus-mediated FGF21 (Ad-FGF21).The profile changes of blood glucose and blood lipid were evaluated at 120 min or 4 weeks after FGF21 administration.Meanwhile, the molecular mechanism was ex-plored by in vitro study.RESULTS: Treatment of db/db mice with recombinant human FGF21 protein significantly re-duced blood glucose and triglyceride levels at 120 min after FGF21 administration , but these changes were comparable in U0126-treated mice .Furthermore , abnormal glucose and triglyceride levels , and glucose and insulin tolerance were strong-ly improved in db/db mice as accompanied with decreasing body fat content after 4 weeks of ad-FGF21 administration .In-terestingly, treatment with or without U0126 did not influence these effects of FGF21.Mechanically, treatment with Ad-FGF21 significantly upregulated the protein levels of p-Erk1/2 and peroxisome proliferator-activated receptor γ( PPARγ) as well as the expression of adiponectin at mRNA and protein levels in adipose tissues .However , treatment with or without U0126 did not change the profiles .On the other hand , in vitro experiments also indicated that treatment of adipocytes with recombinant human FGF 21 protein significantly activated Erk 1/2 phosphorylation , and upregulated the expression levels of PPARγand adiponectin (P<0.05).However, pre-administration of U0126 did not affect the profiles.CONCLUSION:Pharmaceutical inactivation of Erk 1/2 by U0216 does not affect the biological function of FGF 21 to regulate blood glucose balance and improve abnormal blood lipids in vivo.

Clinical features and management of Crohn's disease in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>An increasing incidence of Crohn's disease has been found in China in recent years. Our study has been focused on evaluating the diversity of the clinical manifestations of Crohn's disease in order to improve early diagnostic accuracy and therapeutic efficacy.</p><p><b>METHODS</b>Thirty patients with active Crohn's disease were enrolled and their clinical data, including diagnostic and therapeutic results, were analyzed. Endoscopy combined with histological examination of biopsy specimens provided characteristic features of the disease. Transabdominal bowel sonography (TABS) was used for detecting intestinal complications. Nutritional supportive therapy was given to 20 subjects with active cases of the disease.</p><p><b>RESULTS</b>Most patients were young adults with a higher proportion of females to males (ratio: 1.14:1). The disease affects any segment or a combination of segments along with the alimentary tract (from the mouth to the anus). In this study, the colon and small bowel were the major sites involved. Recurrent episodes of abdominal pain in the right lower quadrant and watery diarrhea were the most common symptoms. Granulomas were identifiable in nearly one-third (30.8%) of all biopsy specimens. In moderate cases of the disease, remission was achieved more quickly through the use of oral prednisone therapy than with SASP or 5-ASA. Beneficial effects on the host's nutritional status were observed. Immunosuppressives were used on an individual basis and showed variable therapeutic effects. Sixteen patients had surgery due to intestinal obstruction or failure to respond to drug therapies. Rapid improvement after surgery was reported.</p><p><b>CONCLUSION</b>Endoscopy (with biopsy) and TABS were both crucial procedures for diagnosis. SASP (or 5-ASA) and prednisone were effective as inductive therapies. Azathioprine has demonstrable benefits after induction therapy with prednisone. Surgery, as an alternative treatment, provided another effective choice in selected patients.</p>

Effects of curcumin on the expression of cytokines in trinitrobenzene sulphonic acid induced colitis / 中华消化杂志

Objective To investigate the therapeutic effects of curcumin(Cur)on trinitrobenzene sulphonic acid(TNBS)induced colitis and to investigate cytokines change in colon mucosa,spleen and sera.Methods Colitis was induced in SD rats by intrarectal injection of TNBS(100 mg/kg).Experi- mental animals were divided into negative control group,TNBS group and Cur therapeutic group(Cur, 30 mg?kg~(-1)?d~(-1),intraperitoneal injection).Expression of cytokines mRNA in colon mucosa was observed by RT-PCR,intracellular cytokines of interferon(IFN)-?and interleukin(IL)-4 in splenocytes were detected by flow cytometry(FCM),concentrations of IFN-?and IL-4 in sera were determined by enzyme-link immunosorbent analysis(ELISA).Results After treatment with Cur,macroscopic scores (3.9?1.0 vs.2.2?0.7),myeloperoxidase(MPO)activity(15.0?2.6 vs.7.3?1.4),mRNA of IFN-?(1.02?0.07 vs.0.06?0.02,mRNAof IL-12(0.29?0.05 vs.0.11?0.01)and the ratio of IFN-?/IL-4(11.44?0.97 vs.0.38?0.10)in colon mucosa,proportion of IFN-?CD4~+(31.7?7.5 vs. 21.1?3.7)and the ratio of IFN-?/IL-4 CD4~+(19.9?5.1 vs.6.1?1.8)in splenocytes,concentra tions of IFN-?[(1528?159)pg/ml vs.(513?14)pg/ml] and the ratio of IFN-?/IL-4(19.5?4.1 vs. 4.2?0.6)in sera were all decreased(P＜0.05 or P＜0.01).Meanwhile,mRNA of IL-4(0.09?0.01 vs.0.15?0.04)and IL-10(0.28?0.08 vs.0.63?0.12)in colon mucosa,proportion of IL-4 CD4~+ (1.6?0.5 vs.3.4?1.1)in splenocytes and concentrations of IL-4 in sera[(81?15)pg/ml vs.(124?20) pg/ml] were all increased after the treatment of Cur(P＜0.05 or P＜0.01).Conclusions Cur showed ther- apeutic effects on TNBS-induced colitis,and the mechanism might be through regulating the balance of Th1/ Th2 in colon locally and systematically.