Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα.Each group of mice was matched with a similar group of sham control animals.Macroscopic and histological features were scored blindly.Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage.RESULTS:DSS produced submucosal erosions,ulcers,inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc.The effect was more pronounced in the latter group (vs Zn diet,P < 0.02).Myeloperoxidase activity (vs controls,P < 0.02) and DNA adducts,greatly elevated in the DSS fed colitis group (vs controls,P < 0.05),were significantly reduced in the treated groups,with a more remarkable effect in the group receiving combined therapy (vs standard diet,P < 0.04).CONCLUSION:DSS induces colonic inflammation which is modulated by the administration of anti-TNFα.Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.

Silencing of Astrocyte Elevated Gene-1 (AEG-1) inhibits the proliferative and invasive potential through interaction with Exostosin-1 (EXT-1) in primary and metastatic colon cancer cells

Colon cancer is the third major cause of cancer deaths,accounting for about 8%in terms of mortality globally.The present study aims to explore the effect of silencing Astrocyte Elevated Gene-1(AEG-1),a metastasis mediating factor,and how it interacts with Exostosin-1(EXT-1)protein to inhibit the proliferative and invasive potential in colon cancer cells.Forward siRNA transfection was performed using AEG-1 siRNA in SW480 and SW620 colon cancer cell lines,and the expression levels of mRNA and protein were analyzed by Real-time PCR and Immunofluorescence.A simple bioinformatics approach was carried out to identify the possible interactions between AEG-1 and EXT-1 using Easy Networks and Pathway Commons Database.Cell survival and clonal efficiency were determined using Cell Counting Kit-8 assay and clonogenic assay,apoptosis using flow cytometry analysis,migration and invasion using scratch and Transwell assays,respectively.Forward siRNA transfection significantly suppressed the expression of AEG-1 in mRNA and protein levels on SW480 and SW620 colon cancer cells.From our results,we found that EXT-1 mRNA and protein level was significantly upregulated in AEG-1 siRNA transfected cells.Moreover,treatment with AEG-1 siRNA inhibited the proliferation,clonogenic ability,migration,and invasion and also induced apoptosis.Through the bioinformatic approach,our data analyses pointed towards the crosstalk between AEG-1 and EXT-1 mediated through Patched-1(PTCH-1)protein.Our current results demonstrated that silencing AEG-1 can restrain cell proliferation,migration,and invasion,ultimately leading to apoptosis.In AEG-1 siRNA transfected cells,PTCH-1 activity might be modulated by several genes and,in turn,affects the EXT-1 activity.Collectively,these observations not only provide insight into the interplay between AEG-1 and EXT-1 but also suggest that AEG-1 may represent a possible candidate therapeutic target through interaction with EXT-1 in colon cancer.

千分之一效能白砷剂改善慢性砷中毒症状的初步临床观察(英文)

背景:全世界有数以百万计的人饮用砷污染的地下水,而目前尚未有缓解慢性砷中毒症状的有效制剂。文献报道白砷剂LM0/3作为一种顺势疗法强化制剂,对于砷中毒症状有一定的治疗作用。目的:本研究旨在验证白砷剂LM0/3对由于生活环境所致而长期饮用砷污染水的人群的慢性砷中毒症状的缓解作用。设计、场所、对象和干预措施:本研究为双盲安慰剂对照研究,参加本研究的28名志愿者来自印度西孟加拉邦纳迪亚区一村落,该村无不含砷的饮用水可用,水井中的含砷量为55～95μg/mL。受试者分别服用药物或安慰剂,在参加试验前及2个月后试验结束时提供血、尿样本。另有18名来自无砷污染饮用水村的志愿者提供血、尿样本作为阴性对照。主要结局指标:测量受试者血、尿样本中的砷含量,各类中毒生物标记物及病理生理指标。结果:28名受试者中,14名愿意提供血、尿样本,其余14名退出试验。受试者的血、尿样本检测出砷的浓度升高,碱性磷酸酶及酸性磷酸酶水平升高,脂质过氧化反应及谷胱甘肽活性升高,血糖、三酰甘油、总胆固醇及低密度脂蛋白胆固醇水平升高,天门冬氨酸氨基转移酶及丙氨酸氨基转移酶水平、γ谷氨酰转移酶及葡萄糖6磷酸脱氢酶含量降低,高密度脂蛋白胆固醇水平及红细胞压积降低。2个月后,用药组的上述指标均有所改善,基质金属蛋白酶活性较安慰剂组有所降低。结论:在尚未有更好的医疗条件和治疗手段的情况下,使用白砷剂LM0/3在饮用水受砷污染地区作为暂时的治疗手段以缓解生活在这些地区的人们的慢性砷中毒症状有一定的可行性。