Human filarial proteins attenuate chronic colitis in an experimental mouse model

Encouraged by our earlier results of promising therapeutic effect of filarial recombinant proteins BmALT2, BmCys and WbL2 individually in the mouse model of acute ulcerative colitis, in this study, these proteins have been explored individually and in different combinations for their therapeutic potential in dextran sulphate sodium (DSS)‐induced chronic colitis mice. These mice, treated with filarial proteins, showed reduced disease parameters including body weight loss, disease activity index, macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Among various treatment schemes, rBmALT2 + rBmCys which showed most pronounced therapeutic implication was found to downregulate the mRNA expressions of IFN‐γ and TNF‐α and upregulate IL‐10 and TGF‐β expression in the splenocytes. Also, increase in level of IgG1 and IgG2a isotypes in the sera of rBmALT2 + rBmCys‐treated colitis mice was noted. Activated NF‐κB level was found to be reduced in the colon of treated colitis mice compared to untreated one. In conclusion, filarial proteins in combination have been shown to improve the clinicopathologic status of chronic colitis through suppression of pro‐inflammatory immune response most possibly in NF‐κB‐dependent manner. We propose this therapeutic strategy to be tested further to be considered as an effective option in chronic colitis.     

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

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Inhibition of Interleukin-1β by Canakinumab and Cardiovascular Outcomes in Patients With Chronic Kidney Disease

Background

Inflammation contributes to chronic kidney disease (CKD), in part mediated through activation of interleukin (IL)-1β by the NLRP3 inflammasome within the kidney. This process also likely contributes to the accelerated atherosclerosis associated with nephropathy.

糖尿病大鼠肾组织中miR-21和SnoN表达的变化

目的探讨糖尿病(DM)大鼠肾组织中微小核糖核酸-21(miR-21)和核转录共抑制因子(SnoN)在肾纤维化过程中的表达变化及其可能机制。方法用链脲佐菌素复制DM大鼠模型,并设对照组(NC),每组n=8。10周后处死大鼠,观察肾组织形态变化;免疫组织化学染色、Western blot及RT-q PCR检测miR-21、SnoN、转化生长因子-β1(TGF-β1)、Smad3、p-Smad3(Ser423/425)、E钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)、胶原蛋白Ⅰ(collagenⅠ)和胶原蛋白Ⅲ(collagenⅢ)的表达。结果与对照组相比,DM组肾组织p-Smad3(Ser423/425)、TGF-β1和α-SMA蛋白表达增加(P0.05),SnoN、E-cadherin蛋白表达减少(P0.05),但SnoN mRNA和miR-21表达明显上调(P0.05),并伴有collagenⅠ、collagenⅢ和FN在间质沉积增多。结论 TGF-β1可能上调miR-21表达,抑制SnoN翻译水平的表达,促进DN的纤维化病变。     

PTPN13在人胃癌组织和胃癌SGC-7901细胞系中的表达及其对细胞增殖和侵袭的影响

目的分析PTPN13在人胃癌组织中及胃癌SGC-7901细胞系中的表达及其对细胞增殖、侵袭的影响。方法收集106例胃癌患者的胃癌组织及癌周正常组织标本。常规培养SGC-7901细胞并分为pc DNA3.1-PTPN13质粒转染组和未转染组。免疫组织化学法检测组织中的PTPN13表达;分析PTPN13表达与患者性别、年龄、肿瘤部位、肿瘤大小、浸润深度及转移的关系;Kaplan-Meier曲线分析不同PTPN13表达患者生存率的差异;CCK-8法检测细胞的增殖能力;Trans-well试验分析侵袭能力;Western blot检测E-cadherin、Snail及MMP9的表达。结果胃癌组织中的PTPN13阳性率低于癌周正常胃组织(31%vs 83%,P0.05);PTPN13的表达与肿瘤直径、浸润深度、淋巴结和远隔器官转移情况有关(P0.05);PTPN13阴性的胃癌患者2生存率较低;PTPN13过表达可以降低SGC-7901细胞的增殖率(P0.05),同时降低其侵袭能力(P0.05);上调PTPN13后SGC-7901细胞上皮化标志物E-cadherin表达增加,而间质化标志物Snail和MMP9表达减少。结论 PTPN13在胃癌组织和胃癌细胞中具有肿瘤抑制作用,较低的PTPN13表达提示患者预后不良。PTPN13具有成为胃癌的治疗诊断或治疗靶点的潜力。     

尾加压素Ⅱ促进大鼠心肌胶原蛋白表达及乳鼠心肌成纤维细胞的增殖

目的探讨尾加压素Ⅱ(UⅡ)对大鼠心肌纤维化的影响。方法腹主动脉缩窄术建立慢性压力超负荷大鼠心力衰竭模型,大鼠分为假手术组、造模4、8和12周组。利用Western blot分析心肌组织中UⅡ、G蛋白偶联受体(GPR14)、胶原Ⅰ(col-Ⅰ)、Ⅲ(col-Ⅲ)及蛋白激酶A(PKA)的表达。体外培养乳鼠成纤维细胞,分为对照组、UⅡ处理组、UⅡ+KT5720处理组及UII+SB-611812组。镜下观察及CKK-8法检测细胞增殖。结果模型组大鼠心肌组织中UⅡ、GPR14、col-Ⅰ、col-Ⅲ蛋白及PKA的表达显著增加,且呈时间依赖性。UⅡ促进乳鼠成纤维细胞(CFs)的增殖(P0.05),而KT5720、SB-611812可抑制UⅡ对乳鼠成纤维细胞的促增殖作用。结论 UⅡ及其受体系统促进大鼠心肌纤维化的发生发展。     

紫杉醇联合奥沙利铂对非小细胞肺癌模型小鼠的治疗作用

目的观察紫杉醇联合奥沙利铂对荷瘤裸鼠非小细胞肺癌治疗效果以及对PDCD5和XIAP表达的影响。方法制备裸鼠肺癌荷瘤模型,将荷瘤小鼠随机分为空白组、0.9%氯化钠溶液组、奥沙利铂组、紫杉醇组和紫杉醇联合奥沙利铂组;q-PCR检测各组PDCD5和XIAP基因表达水平;Western bolt分析各组PDCD5和XIAP蛋白表达情况;对比分析各组肿瘤组织重量。结果紫杉醇联合奥沙利铂组PDCD5 mRNA表达水平最高(P0.01),XIAP mRNA表达水平最低(P0.01);紫杉醇联合奥沙利铂组PDCD5蛋白表达最高(P0.01),XIAP蛋白表达最低(P0.01);对比各分组肿瘤组织重量,紫杉醇联合奥沙利铂组肿瘤质量最小(P0.01)。结论紫杉醇联合奥沙利铂化疗能显著增加PDCD5表达和降低XIAP表达,能使已发生的非小细胞肺癌组织质量显著减少。     

低氧培养促进大鼠髓核间质干细胞增殖

目的研究低氧培养对大鼠髓核间质干细胞(NPMSCs)增殖的影响。方法分离大鼠尾椎髓核获得NPMSCs并进行体外扩增培养,观察细胞形态,流式细胞仪鉴定细胞免疫表型。取第3代NPMSCs分为常氧组和2%低氧组,分别培养7 d及14 d,观察细胞形态;MTT法检测细胞增殖;流式细胞仪检测细胞活力和RT-q PCR检测低氧诱导因子1α(HIF-1α)、葡萄糖转运蛋白1(GLUT-1)、血管内皮生长因子(VEGF)、沉默信息调节蛋白1(SIRT1)及SIRT6的mRNA表达情况。结果原代NPMSCs细胞早期可形成葵花样细胞集落,传代后细胞增殖明显加快,细胞形态以纺锤形为主。第3代细胞高表达干细胞相关阳性表面抗原分子,低表达干细胞相关阴性表面抗原分子。低氧组细胞形态以多角形为主,细胞更容易聚集成团块,且细胞增殖速度明显加快(P0.05),细胞凋亡率明显下降(P0.05)。低氧组HIF-1α、VEGF、GLUT-1、SIRT1及SIRT6表达量明显高于常氧组(P0.05)。结论 2%O2的低氧环境促进髓核间质干细胞增殖,其机制可能与SIRT1及SIRT6介导的HIF-1α信号通路有关。     

High-sensitivity C-reactive protein (hs-CRP) in systemic lupus erythematosus patients without cardiac involvement; relation to disease activity,damage and intima-media thickness

Aim of the workTo assess the high sensitivity C-reactive protein (hs-CRP level) in systemic lupus erythematosus (SLE) patients without cardiac involvement and find its relation with clinical and laboratory findings, disease activity, damage index and intima-media thickness (IMT).Patients and methodsForty-five female SLE patients were recruited in the present study without any cardiac involvement. History taking, examination and laboratory investigations were performed for patients. Disease activity was evaluated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage by the Systemic Lupus International Collaborating Clinics (SLICC) index. Thirty age matched female healthy subjects were considered as a control group. hs-CRP was measured quantitatively by microplate immunoenzymometric assay and the IMT measured by ultrasonography.ResultsThe hs-CRP in the patients was significantly higher (4.84 ± 3.91 mg/l) compared to the control (1.74 ± 0.61 mg/l) (p < 0.001). The IMT in the patients was significantly increased (0.72 ± 0.37 mm) compared to the control (0.54 ± 0.15 mm) (p 0.004). There was no difference in the level of hs-CRP according to the presence or absence of clinical manifestations. However, it was significantly higher in those with positive DNA (5.71 ± 4.36 mg/L) compared to those with negative results (3.12 ± 1.97 mg/L) (p 0.009). There was a significant correlation of the hs-CRP level with the IMT (r 0.49, p 0.001) and SLEDAI (r 0.67, p < 0.001).ConclusionsThese findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of future cardiac events. Measuring hs-CRP may be useful as a marker of disease activity, increased IMT and subclinical atherosclerosis in SLE especially those with positive ds-DNA.     

X连锁凋亡抑制蛋白和线粒体第二激活因子在锰诱导大鼠生精细胞凋亡蛋白酶表达中的调节作用

目的:研究氯化锰导致的大鼠生精细胞半胱氨酸天冬氨酸蛋白酶-9(caspase-9)及凋亡蛋白酶活化因子-1(Apaf-1)表达中X连锁凋亡抑制蛋白(XIAP)和线粒体第二激活因子(Smac)的调节机制,探讨锰导致的雄性不育机制。方法:雄性SD大鼠随机分为对照组、低剂量(15 mg/kg MnCl_2)和高剂量(30 mg/kg MnCl_2)组,腹腔注射MnCl_2 4周和6周,免疫组织化学检测生精细胞caspase-9、Apaf-1、XIAP和Smac表达。结果:与对照组相比较,各组生精细胞caspase-9、Apaf-1和Smac表达均显著升高,XIAP表达降低。同时间的高剂量组与低剂量组比较,同剂量的6周组与4周组比较,生精细胞caspase-9、Apaf-1和Smac表达均显著升高,XIAP表达降低。各组caspase-9与Apaf-1表达呈正相关,XIAP与Smac表达呈负相关。结论:锰可促进生精细胞caspase-9、Apaf-1和Smac表达,抑制XIAP表达,导致细胞凋亡,产生雄性生殖毒性效应。