Alantolactone,a sesquiterpene lactone,inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling

Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal plants such as Inula helenium, has been identified to have attractive anticancer activity. However, its role in the inhibition of angiogenesis during tumor development remains unclear. In this study, we found ALA can inhibit the proliferation, motility, migration, and tube formation of human umbilical vein endothelial cells. ALA also restrained angiogenesis in chick embryo chorioallantoic membrane and delayed the growth of human MDA‐MB‐231 breast cancer xenograft in mice through angiogenesis inhibition. Furthermore, ALA suppressed the phosphorylation of vascular endothelial growth factor receptor 2 and its downstream protein kinase including PLCγ1, FAK, Src, and Akt in endothelial cells. Taken together, the antiangiogenic activity of ALA and its molecular mechanism are identified for the first time, indicating that ALA may be a potential drug candidate or lead compound for antiangiogenic cancer therapy.     

第九届胆道闭锁与小儿肝移植论坛会议纪要

由天津市第一中心医院、天津市儿童医院、《中华小儿外科杂志》编辑部、《中华器官移植杂志》编辑部联合主办的第九届"胆道闭锁与小儿肝移植论坛",于2020年10月10日至2020年10月11日在天津顺利召开,来自全国各地100余位代表参会。会议内容报道如下。     

KIF2A regulates ovarian development via modulating cell cycle progression and vitollogenin levels

The kinesin superfamily of proteins (KIFs) are microtubule motor proteins that use the hydrolysis of ATP to power directional movement along microtubules. KIFs induce microtubule depolymerization to regulate the length and dynamics of microtubules in a variety of cell processes and structures, including the mitotic and meiotic spindles and centriole and interphase microtubules. KIF plays a significant role in the transport of organelles, protein complexes and mRNAs. The brown planthopper (Nilaparvata lugens) is a major insect pest in rice paddy fields. Ovarian development is regulated by multiple factors, including endocrine factors. The role of KIFs in brown planthopper ovarian development remains unknown. We found that downregulation of KIF2A significantly compromised the development and eclosion of the brown planthopper, delayed ovarian cell cycle progression, disrupted ovarian development, reduced the expression of MCM genes required for DNA replication and significantly reduced the number of nuclei in the follicles. We also found a significant reduction in Vg mRNA and protein levels. We conclude that downregulation of KIF2A disrupts the cell cycle progression of cells. Alternatively, the ovarian phenotype could be an indirect effect of a compromised trophic cord. In summary, KIF2A regulates ovarian development via modulating cell cycle progression and/or vitollogenin transportation.     

Diagnosis of double-chambered left ventricle by echocardiogram and cardiac magnetic resonance imaging: A rare case in an adult

Double-chambered left ventricle (DCLV) is a very rare malformation which is congenital. In most cases, the left ventricle (LV) is divided into two parallel chambers by a septum or aberrant muscular structure, with fewer superior–inferior arrangement. Here, we present the case of an asymptomatic 25-year-old man who was diagnosed with superior–inferior arrangement DCLV on transthoracic echocardiography and cardiac magnetic resonance (CMR). DCLV generally does not cause serious outcomes. Owing to absence of any symptoms, no treatment was provided, and the patient was regularly followed up.     

Dynamic features of placebo effects addressing persistent insomnia disorder: A meta‐analysis of placebo‐controlled randomized clinical trials

It has been accepted knowledge that placebo effects have been significant in insomnia clinical trials. However, the dynamic features of placebo effects have not been clarified. Our aim was therefore to conduct a meta‐analysis of placebo‐controlled randomized clinical trials to characterize the dynamic features of placebo effects addressing persistent insomnia disorder. We performed a comprehensive literature search for randomized, placebo‐controlled, double‐blind clinical trials evaluating the efficacy of therapeutic regimens addressing persistent insomnia disorder. We pooled separate effect size estimates (Hedge's g) of placebo and regimen conditions across trials for outcome measures, and multilevel mixed‐effects models were used to explore potential sources of heterogeneity. The placebo effects were significant and robust to improve the symptoms of insomnia, and subjective measures were significantly smaller than objective measures (p < .001), but placebo response rates were nearly identical between subjective and objective measures. The overall placebo effects were influenced by publication year (p = .015), treatment duration (p = .010), sample size (p < .001) and therapeutic regimen (p < .001). Placebo effects showed a diphasic feature within treatment duration: initially a decrease and subsequently being stable; a sustained decline trend after withdrawals; and a steady‐to‐upward trend for a mixed therapeutic regimens in a large‐scale period over decades. The dynamic features of placebo effects addressing persistent insomnia disorder may lead to the development and validation of dosing strategies that require less medication exposure to maintain clinical effects.     

Study on the characteristics and mechanisms of nicosulfuron biodegradation by Bacillus velezensis CF57

Nicosulfuron is one of the main sulfonylurea herbicides that have been widely used to protect maize crops. A total of 10 nicosulfuron-degrading strains were isolated from the intestine tract of earthworm Eisenia foetida. Among them, Bacillus velezensis CF57 with the highest degradation efficiency was selected and studied in detail. The degradation characteristics of CF57 showed that it was able to effectively degrade nicosulfuron in a wide range of temperature, pH, and a low inoculation amount, and the response surface analysis revealed that the optimum degradation conditions were 30.8 °C, pH 6.31, and inoculation amount 3.04%. Meanwhile, CF57 could degrade high-concentration nicosulfuron efficiently and posed a broad degradation spectrum of other sulfonylurea herbicides. Furthermore, the localization of degradation enzyme indicated that the nicosulfuron-degrading enzyme was an extracellular fraction. By analyzing the metabolites of nicosulfuron, it could be further determined that the degradation of nicosulfuron by strain CF57 was mainly through the extracellular enzyme, and its possible degradation pathway was mainly derived from the cleavage of the C–N bond of the sulfonylurea bridge. These results may provide new insights into bioremediation of nicosulfuron-contaminated environments and enrich the resources of degrading bacteria of sulfonylurea herbicides.