The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs. 相似文献
Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer. 相似文献
Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed. 相似文献
Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.
Methods: [11C]WAY100635, [18F]altanserin and positron emission tomography were used to compare 5-HT1A and 5-HT2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.
Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.
Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents. 相似文献