Serum vaspin levels in type 2 diabetic patients are associated with the severity of lower limb vascular lesion / 中国医师杂志

Objective To explore the association between serum vaspin levels and the severity of the lower extremity vascular lesions in type 2 diabetes mellitus (T2DM) patients.Methods According to the lower extremity artery plaque,stenosis and intima-media membrane thickening severity score,92 cases of T2DM patients were divided into three groups:simple diabetes group (DM1 group) (32 cases),mild diabetic lower limb vascular lesion group (DM2 group) (33 cases),and moderately severe diabetic lower limb vascular lesion group (DM3 group) (27 cases).Twenty-six age-and gender-matched apparently healthy controls (control group) were recruited as well.Systolic blood pressure (SBP),ankle-brachial index (ABI),insulin resistance index (HOMA-IR),and other indicators were determined,serum vaspin was measured by enzyme-linked immunosorbent assay.Results After adjustment for age and gender,the DM1 group had a significantly higher serum vaspin level than control group (P ＜0.01),while for the DM2 and DM3 groups,serum vaspin levels were significantly lower than the DM1 group (P ＜ 0.01).Partial correlation analysis showed that serum vaspin was inversely associated with HOMA-IR (r =-0.461,P =0.001)and positively correlated with ABI (r =0.462,P =0.001).Logistic regression analysis demonstrated that SBP,ABI and fasting serum vaspin levels were significantly associated with the presence of the lower extremity vascular lesions in type 2 diabetes.Conclusions Serum vaspin levels were significantly elevated in simple type 2 diabetic patients while the reduction of its level might be associated with the formation of lower extremity vascular lesions in type 2 diabetic patients.

Advances in antiviral therapy targeting to hepatitis C virus NS3/4A protease / 中华临床感染病杂志

Hepatitis C virus (HCV) genome is of high variation,which results in persistent infection of HCV and increases the incidence of liver cirrhosis and hepatocellular carcinoma.Following the successful paradigm established for HIV protease inhibitors,HCV NS3-4A serine protease has been selected as the main target for the development of small molecule antiviral agents.In this article,we review recent progress in the discovery and development of HCV NS3-4A protease inhibitors,and discuss their antiviral activities,pharmacokinetic properties,side effects and resistance profiles.

Effects of tissue factor pathway inhibitor-2 on the growth and angiogenesis of subcutaneous tumor xenografts in nude mice established from human liver cancer cells / 肿瘤

Objective: To investigate the effects of TFPI-2 (tissue factor pathway inhibitor 2) on the growth and angiogenesis of subcutaneous tumor xenografts in nude mice established from human liver cancer cells. Methods: The Hep3B cells stably expressing TFPI-2 (Hep3B-TFPI-2 group) and the Hep3B cells transfected with empty vector PCDNA3.1 (Hep3B-V group) or without transfection (Hep3B-P group) were subcutaneously transplanted into nude mice respectively to generate subcutaneous tumor xenografts. The volume of tumor xenograft was measured every three days, and the growth curve of tumor xenograft was drawn when the subcutaneous tumor xenograft was visible. The nude mice were killed three weeks after transplant, the volume of tumor xenograft was measured, and the total RNAs and proteins in tumor xenografts were extracted. The mRNA and protein expressions of TFPI-2 and VEGF (vascular endothelial growth factor) in tumor xenografts were analyzed by RFQ-PCR (real-time fluorescence quantitative PCR) and Western blotting, respectively. The expression of TFPI-2 protein and the MVD (microvessel density) in tumor xenografts were observed by immunohistochemistry. Results: The eventual tumor volume of tumor xenografts in Hep3B-TFPI-2 group was apparently smaller than those in Hep3B-V group and Hep3B-P group (both P < 0.05). The expression of mRNA and abundance of protein of TFPI-2 in Hep3B-TFPI-2 group were significantly higher than those in the other two groups (P < 0.05); while the expression of mRNA and abundance of protein of VEGF in Hep3B-TFPI-2 group were apparently lower than those in the other two groups. Compared with Hep3B-V group and Hep3B-P group, the inhibitory rates of VEGF protein expression in Hep3B-TFPI-2 group were 19.8% and 23.5%, respectively (P < 0.05). The MVD in Hep3B-TFPI-2 group was apparently lower than those in the other two groups (P < 0.05). Conclusion: TFPI-2 can significantly inhibit the growth and angiogenesis of subcutaneous tumor xenografts in nude mice established from hepatocarcinoma Hep3B cells. Copyright © 2013 by TUMOR.

Expression and significance of matriptase and HAI-1 in prostate cancer / 中国医师杂志

Objective To investigate the expression and significance of Matriptase and HAI-1 protein in prostate cancer (CaP). Methods Specimens of 46 prostate cancers,20 benign prostate hyperplasias (BPH),10 high-grade intraepithelial neoplasias (PIN),and 10 normal prostates (NP) were used. Expressions of Matriptase and HAI-1 proteins in specimens were detected by SP of immunohistochemistry. The results were analyzed in relation to the clinicopathological data. Results The protein levels of Matriptase in CaP tissues were significantly higher than PIN tissues(Z＝-2.150,P＝0.032),and the expression of matriptase in CaP and PIN was higher than that in BPH and NP (Z＝-3.270,P＝0.001;Z＝-2.817,P＝0.005). No statistically significant difference was observed between BPH and NP group (Z＝-0.895,P＝0.325). A progressive increase in the protein levels of Matriptase was observed with increasing tumor grade (rs＝0.583,P＜0.01) and clinical stages（rs＝0.611,P＜0.01）in CaP specimens. The protein levels of HAI-1 in BPH and NP tissues were significantly higher than CaP and PIN tissues（Z＝-3.277,-3.315,P＜0.01）,the levels of HAI-1 in PIN were higher than CaP (Z＝-2.310,P＝0.020). No statistically significant difference was found between BPH and NP (Z＝-0.872,P＝0.330). A progressive decrease in the protein levels of HAI-1 was observed with increasing tumor grades（rs＝-0.634,P＜0.01） and clinical stages（rs＝-0.521,P＜0.01）. The expressions of Matriptase and HAI-1 in CaP tissues showed negative correlations（rs＝-0.712,-0.560,-0.465,respectively,P＜0.01）. Conclusions The abnormal expressions of Matriptase and HAI-1 proteins may be important events during the progression of CaP in humans. Matriptase and HAI-1 Protein may be used as parameters for assessing the malignancy and prognosis of CaP.

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cut and exposed tongue wounds

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.