Monkeypox: A Comprehensive Review

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.     

枳实含药血清对大鼠胃窦平滑肌细胞收缩效应及细胞内钙离子浓度、钙调蛋白表达的影响

目的:观察单味中药枳实含药血清对大鼠胃窦平滑肌细胞收缩效应及细胞内Ca2+、钙调蛋白表达的影响.方法:按照血清药理学通法制备大鼠枳实含药血清,将血清分为枳实组(10%、20%、50%枳实含药血清)、空白血清对照组,酶解法提取胃窦平滑肌细胞并进行培养,倒置显微镜下观察各组对胃窦平滑肌细胞收缩效应,激光共聚焦显微镜技术检测各组加药前后胃窦平滑肌细胞内Ca2+浓度变化,免疫组织化学方法观察各组对胃窦平滑肌细胞内钙调蛋白的表达.结果:10%、20%、50%枳实含药血清对胃窦平滑肌细胞收缩及细胞内Ca2+荧光强度的影响呈药物剂量依赖关系,细胞收缩、细胞内Ca2+荧光强度随药物浓度的增高而增强(P<0.05),20%、50%枳实含药血清与空白血清对照组对胃窦平滑肌细胞收缩、细胞内Ca2+荧光强度差异有统计学意义(P<0.05),50%枳实组与空白血清对照组对胃窦平滑肌细胞内钙调蛋白表达差异有统计学意义(P<0.05).结论:枳实含药血清可以促进胃窦平滑肌细胞收缩,其机制可能与增加细胞内Ca2+浓度、调节钙调蛋白的表达有关.     

Biophysical and molecular docking studies of naphthoquinone derivatives on the ATPase domain of human Topoisomerase II

Numerous naphthoquinone derivatives, such as rhinacanthins function as anticancer drugs, which target hTopoII. The structure of hTopoII contains both an ATPase domain and a DNA binding domain. Several drugs bind to either one or both of these domains, thus modifying the activity of hTopoII. The naphthoquinone esters and amides used in this study showed that their hTopoIIα inhibitory activity was inversely proportional to ATP concentration. In order to better characterize the inhibitory action of these compounds, sufficient quantities of soluble functional hTopoII-ATPase domain were required. Therefore, both the alpha and beta isoforms of the hTopoII-ATPase domain were over-expressed in Escherichia coli. The hTopoIIα-ATPase activity was reduced in the presence of naphthoquinone derivatives. Additionally, a molecular docking study revealed that the selected naphthoquinone ester and amide bind to the ATP-binding domain of hTopoIIα. Collectively, the results here provide for the first time a novel insight into the interaction between naphthoquinone esters and amides, and the ATP-binding domain of hTopoIIα. The further elucidation of the mechanism of action of the naphthoquinone esters and amides inhibitory activity is essential.