Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischem...
详细信息
Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischemic period. The deleterious effects of TNFα seem to be related to the triggering of apoptosis. This study has been designed to determine if different doses of TNFα, administered before the ischemic period, have the same effect on infarct size and on activation of caspase-3 and-8, two enzymes involved in apoptosis. Four groups, using a porcine model of myocardial infarction, have been used: placebo and TNFα (0.1 μg/kg;1 μg/kg and 3 μg/kg). All administered 15 minutes before a 50 minutes occlusion of the left anterior descending artery. Myocardial infarct size has been determined at 3 hours of reperfusion. In a subgroup of animals, reperfusion period has been limited to 15 min to determine the activity of caspase-3 and-8 by spectrofluorometry. Results indicated that infarct size is significantly smaller in groups 0.1 μg/kg and 1 μg/ kg as compared to the placebo group. In contrast, the 3 μg/kg group presented an infarct size similar to the placebo group. Activity of caspase-3 and-8 is reduced in the ischemic region in groups 0.1 and 1 μg/ kg as compared to the placebo group whereas activity in the 3 μg/kg group was similar to the placebo. The results obtained indicated that a low dose of TNFα administered before the ischemic period reduces infarct size, whereas the cardioprotection is lost with the high dose.
While emerging data suggest nucleotide oligomerization domain receptor 1(NOD1),a cytoplasmic pattern recognition receptor,may play an important and complementary role in the immune response to bacterial infection,its ...
详细信息
While emerging data suggest nucleotide oligomerization domain receptor 1(NOD1),a cytoplasmic pattern recognition receptor,may play an important and complementary role in the immune response to bacterial infection,its role in cancer metastasis is entirely ***,we sought to determine the effects of NOD1 on ***1 expression in paired human primary colon cancer,human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting(WB).Clinical significance of NOD1 was assessed using TCGA survival data.A series of in vitro and in vivo functional assays,including adhesion,migration,and metastasis,was conducted to assess the effect of NOD1.C12-iE-DAP,a highly selective NOD1 ligand derived from gram-negative bacteria,was used to activate ***130,a specific NOD1 inhibitor,was used to block C12-iE-DAP *** knockdown(KD)of NOD1 in human colon cancer cells(HT29)was constructed with shRNA lentiviral transduction and the functional assays were thus ***,the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase *** data demonstrate that NOD1 is highly expressed in human colorectal cancer(CRC)and human and murine CRC cell ***,we demonstrate that this increased NOD1 expression negatively impacts survival in patients with ***,we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion,migration and *** effects are predominantly mediated via the p38 mitogen activated protein kinase(MAPK)*** is the first study implicating NOD1 in cancer metastasis,and thus identifying this receptor as a putative therapeutic target.
暂无评论