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排序方式: 共有137条查询结果,搜索用时 15 毫秒
71.
Wang M Chen S Wang S Sun D Chen J Li Y Han W Yang X Gao HQ 《The Chinese journal of physiology》2012,55(2):134-144
Our study investigated the effects of the chemopreventive agent sulforaphane (SFN) on human colon cancer Caco-2 cells and potential underlying mechanisms of the effects. When treated with SFN at hypotoxic levels, UDP-glucuronosyltransferase 1A (UGT1A) was induced in a dose-dependent manner. SFN at 25 μM showed the highest UGT1A-induction activity, inducing UGT1A1, UGT1A8, and UGT1A10 mRNA expression, and increasing UGT-mediated N-hydroxy-PhIP glucuronidation. SFN- induced UGT1A expression may have resulted from Nrf2 nuclear translocation or activation. At higher concentrations, e.g. 75 μM, SFN caused G1/G2 cell cycle arrest and induced apoptosis possibly through reducing anti-apoptotic bcl-2 expression and increasing apoptosis-inducing bax expression in Caco-2 cells. Taken together, these results demonstrated the chemopreventive effects of SFN on human colon cancer Caco-2 cells may have been partly attributed to Nrf2-mediated UGT1A induction and apoptosis induction, and our studies provided theoretic and experimental basis for clinical application of SFN to human colon cancer prevention. 相似文献
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Background
An association between male subfertility and an increased risk of testicular cancer has been proposed, but conflicting results of research on this topic have rendered this theory equivocal. To more precisely assess the association between subfertility and the risk of testicular cancer, we performed a systematic review of international epidemiologic evidence.Principal Findings
We searched the Medline database for records from January 1966 to March 2008 complemented with manual searches of the literature and then identified studies that met our inclusion criteria. Study design, sample size, exposure to subfertility and risk estimates of testicular cancer incidence were abstracted. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird model. All statistical tests were two-sided. We identified seven case-control studies and two cohort studies published between 1987 and 2005. Analysis of the seven case-control studies that included 4,954 participants revealed an overall statistically significant association between subfertility and increased risk of testicular cancer (summary RR = 1.68, 95% CI: 1.22 to 2.31), without heterogeneity between studies (Q = 8.46, P heterogeneity = 0.21, I 2 statistics = 0.29). The association between subfertility and testicular cancer was somewhat stronger in the United States (summary RR = 1.75, 95% CI: 1.01 to 3.02) than it was in Europe (summary RR = 1.53, 95% CI: 1.22 to 1.92). The source of the control subjects had a statistically significant effect on the magnitude of the association (population-based summary—RR = 2.15, 95% CI: 1.11 to 4.17; hospital-based summary—RR = 1.56, 95% CI: 0.93 to 2.61). After excluding possible cryptorchidism, an important confounding factor, we also found a positive association between subfertility and increased risk of testicular cancer (summary RR = 1.59, 95% CI: 1.28 to 1.98). These results were consistent between studies conducted in the United States and in Europe (Q = 0.20, P heterogeneity = 0.66). Of the two cohort studies that reported standardized incidence ratios, both reported a statistically significant positive association between subfertility and increased risk of testicular cancer.Conclusions
Our findings support a relationship between subfertility and increased risk of testicular cancer and apply to the management of men with subfertility, and prevention and diagnosis of testicular cancer. 相似文献75.
Mycobacterium tuberculosis proteasomal ATPase Mpa has a β‐grasp domain that hinders docking with the proteasome core protease
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Defeng Li Lin Bai Shaoqing Yang Jordan B. Jastrab Shuhao Xiao Yonglin Hu Susan Zhang K. Heran Darwin Tao Wang Huilin Li 《Molecular microbiology》2017,105(2):227-241
Mycobacterium tuberculosis (Mtb) has a proteasome system that is essential for its ability to cause lethal infections in mice. A key component of the system is the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds, and translocates protein substrates into the Mtb proteasome core particle for degradation. Here, we report the crystal structures of near full‐length hexameric Mtb Mpa in apo and ADP‐bound forms. Surprisingly, the structures revealed a ubiquitin‐like β‐grasp domain that precedes the proteasome‐activating carboxyl terminus. This domain, which was only found in bacterial proteasomal ATPases, buries the carboxyl terminus of each protomer in the central channel of the hexamer and hinders the interaction of Mpa with the proteasome core protease. Thus, our work reveals the structure of a bacterial proteasomal ATPase in the hexameric form, and the structure finally explains why Mpa is unable to stimulate robust protein degradation in vitro in the absence of other, yet‐to‐be‐identified co‐factors. 相似文献
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CYP2E1-dependent toxicity and up-regulation of antioxidant genes 总被引:5,自引:0,他引:5
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Ethanol and arachidonic acid produce toxicity in hepatocytes from pyrazole-treated rats with high levels of CYP2E1 总被引:5,自引:0,他引:5
Ethanol and polyunsaturated fatty acids such as arachidonic acid were shown to be toxic and cause apoptosis in HepG2 cells which express CYP2E1 but not in control HepG2 cell lines. The goal of the current study was to extend the observations made with the HepG2 cells to non-transformed, intact hepatocytes. Rats were treated with pyrazole to increase CYP2E1 levels, hepatocytes were isolated and placed into culture and treated for varying time points with ethanol or arachidonic acid. Comparisons were made to hepatocytes from saline-treated rats, with low CYP2E1 content. Incubation with ethanol (100 mM) or especially arachidonic acid (60 µM) resulted in loss of viability of hepatocytes from the pyrazole-treated rats, without any effect on the hepatocytes from the saline-treated rats. The toxicity appeared to be apoptotic in nature and was prevented by diallyldisulfide, an inhibitor of CYP2E1. Toxicity was reduced by trolox, an antioxidant. The treatment with ethanol or arachidonic acid resulted in release of cytochrome c into the cytosol fraction, and activation of caspase 3 (but not caspase 1) in hepatocytes from the pyrazole-treated rats but not hepatocytes from the saline-treated rats. The activation of caspase 3 was prevented by diallyldisulfide, by trolox, and by DEVD-fmk. The latter also prevented the toxicity produced by ethanol or arachidonic acid. These results extend previous observations found with HepG2 cells expressing CYP2E1 to intact hepatocytes and suggest that release of cytochrome c and activation of caspase 3 play a role in the overall pathway by which CYP2E1 contributes towards the hepatotoxic actions of ethanol and polyunsaturated fatty acids 相似文献
79.
GCF2是转录抑制因子,为了研究GCF2蛋白在肝癌细胞BEL-7404迁移中的作用,并根据芯片结果验证GCF2调控参与迁移的靶基因,我们采用siR NA沉默GCF2蛋白表达,然后通过transwell实验检测GCF2沉默前后BEL-7404细胞迁移的变化,最后荧光定量RT-PCR和Western blot验证芯片结果中与迁移相关基因的表达。研究结果显示siR NA干扰GCF2成功后进行迁移实验,si RNA-GCF2组,FAM-siR NA-NC组,脂质体组,和未处理野生型BEL-7404组24 h后细胞穿过8滋m微孔滤膜的数目(x±s)分别为41.66±1.52、41.66±1.15、41.33±1.5、18.66±0.577,差异均有统计学意义(p约0.01)。QRT-PCR验证9个候选基因中,MyD 88在si RNA-GCF2组内表达显著高于其余三组(p约0.05)。Western blot检测siR NA干扰GCF2后肝癌细胞BEL-7404的MyD 88的蛋白表达显著高于其余三组(p约0.05)。结果表明si RNA沉默转录因子GCF2蛋白表达可抑制肿瘤细胞BEL-7404迁移,推测GCF2作为转录因子可能通过抑制靶基因MyD 88的表达参与细胞的迁移。 相似文献
80.
Hyperthermia as an anticancer method has been paid increasing attention in recent years. Several studies have shown that hyperthermia can kill tumor cells by inducing apoptosis. However, the underlying molecular mechanisms of hyperthermia-induced apoptosis are largely unknown. To investigate the effects and molecular mechanism of hyperthermia on the apoptosis in renal carcinoma 786-O cells, we firstly examined apoptosis and Ku expression in 786-O cell line treated with heat exposure (42°C for 0-4 h). The results showed that hyperthermia induced apoptosis of 786-O cells, and suppressed significantly Ku80 expression, but not Ku70 expression. Next, we knock-down Ku80 in 786-O cells, generating stable cell line 786-O-shKu80, and detected apoptosis, cell survival and cell cycle distribution. Our data showed higher apoptotic rate and lower surviving fraction in the stable cell line 786-O-shKu80 compared with those in control cells, exposed to the same heat stress (42°C for 0-4 h). Moreover, the results also showed suppression of Ku80 led to G2/M phase arrest in the stable cell line 786-O-shKu80 following heat treatment. Together, these findings indicate that Ku80 may play an important role in hyperthermia-induced apoptosis and heat-sensitivity of renal carcinoma cells through influencing the cell cycle distribution. 相似文献