Lipoic acid inhibited desflurane-induced hippocampal neuronal apoptosis through Caspase3 and NF-KappaB dependent pathway.

Desfluraneis a widely-used general anesthetics. However, recent reports showed its significant side effect in the nervous system. Desflurane could lead to the neuronal death and affect the working memory. Unfortunately, the mechanism underlying the action of desflurane is still not clear and there is still no potent medicine to prevent the lesion in the central nervous system caused by general anesthetics. In this study, we found α-lipoic acid, an antioxidant exerting protective effect on multiple cells tissues, could resist the neurotoxicity caused by desflurane exposure. Lipoic acid possessed strong anti-apoptotic effect on the desflurane-treated hippocampal neurons, which was mediated by the Caspase-3 dependent pathway and NF-kappaB signaling. Collectively, we found a promising candidate to be clinically applied in intervention against the damage in nervous system by the desflurane.

Ovarian carcinoma-infiltrating regulatory T cells were more potent suppressors of CD8(+) T cell inflammation than their peripheral counterparts, a function dependent on TIM3 expression.

Ovarian carcinoma is one of the most severe cancers in women, with a high relapse rate and limited secondary treatment options. To assist research in novel treatment technologies, including CD8(+) T cell-base immunotherapy, we examined the effect of tumor-infiltrating regulatory T cells (Tregs) in inhibiting CD8(+) T cell inflammation. We found that compared to their peripheral blood counterparts, tumor-infiltrating Tregs exhibited more potent inhibitory function, which was associated with higher interleukin 10 (IL-10) production in tumor-infiltrating Tregs. Blockade of T cell immunoglobulin mucin 3 (TIM3), a regulatory molecule overrepresented on tumor-infiltrating Tregs, had significantly reverted Treg-mediated suppression. Moreover, expression of TIM3 on tumor-infiltrating Tregs was directly correlated with tumor size. Together, our results demonstrated that ovarian tumor-infiltrating Treg cells were more immunosuppressive than their peripheral blood counterparts in a TIM3-dependent fashion.

Toll-like receptor 4 gene polymorphism downregulates gene expression and involves in susceptibility to bladder cancer.

Bladder cancer is the ninth most frequent malignancy in China. Toll-like receptor 4 (TLR4) is expressed on various cells and greatly involves in immune responses. Genetic polymorphism may affect the pathogenesis of diseases through various pathways. In the current study, we evaluated the association between genetic polymorphisms in TLR4 and risk of bladder cancer. We also examined the effect of the polymorphisms on gene expression. The TLR4 -729G/C and -260G/C polymorphisms were genotyped in 282 bladder cancer patients and 298 healthy controls in the Chinese population. Results showed that subjects with -729GC genotype are at significantly higher risk of bladder cancer than those with GG genotype [odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.39-4.48, P = 0.002]. Similarly, TLR4 -729C allele revealed a positive association with the disease (OR = 2.39, P = 0.002). The other polymorphism, TLR4 -260G/C, did not present clear correlations with bladder cancer. To understand the function of the polymorphisms, we evaluated TLR4 messenger RNA (mRNA) and protein levels in CD4+ T cells, CD8+ T cells, and monocytes from subjects carrying different TLR4 genotypes. Results revealed that subjects carrying -729GC genotype had significantly downregulated mRNA and protein levels of TLR4 in CD4+ T cells, CD8+ T cells, and monocytes compared to those carrying GG genotype. However, subjects with -260G/C polymorphism did not show any differences in gene expression from immune cells These data suggest that TLR4 polymorphism is associated with increased susceptibility to bladder cancer possibly by downregulating gene expression in various immune cells.

Lysyl oxidase genetic variants affect gene expression in cervical cancer.

Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays important roles in the homeostasis of tumors. The aim of this study was to investigate the association between LOX polymorphisms and cervical cancer, and the effect of these polymorphisms on gene expression. We evaluated two polymorphisms of LOX, rs1800449G/A (G473A) and rs2278226C/G, in 262 cervical cancer cases and 298 healthy controls in the Chinese population. Results showed that the prevalence of rs1800449AA genotype was significantly increased in cases than in controls (p=0.004). Individuals who carried the rs1800449A allele had a 1.56-fold increased risk for cervical cancer than those with the rs1800449G allele (p=0.003). The rs2278226CG genotype also revealed a significantly higher proportion in cases (20.6%) than in controls (7.7%, p<0.001). Interestingly, when analyzing these two polymorphisms with the serum level of LOX, we identified that cervical cancer patients carrying the rs2278226CG genotype had a significantly elevated level of LOX than those with rs2278226CC wild type, whereas the same phenomenon was not observed in controls. The rs1800449 polymorphism did not affect the LOX serum level in either controls or patients. These results suggest that the polymorphisms in the LOX gene may be involved in the development of cervical cancer through various mechanisms.