基于网络药理学与分子对接技术的清瘟护肺颗粒防治新型冠状病毒肺炎(COVID-19)的潜在药效物质研究

本文通过网络药理学和分子对接技术探讨清瘟护肺颗粒防治新型冠状病毒肺炎(COVID-19)的潜在药效物质.首先,通过TCMSP数据库,BATMAN-TCM数据库及TCMIP数据库检索清瘟护肺颗粒中十六味药的化学成分及作用靶点,利用GeneCards和OMIM数据库检索COVID-19的相关疾病靶点.然后,通过venny2...     

凋亡和周期基因芯片研究As2O3对NB4细胞凋亡相关基因表达谱的影响

目的:利用细胞凋亡和周期基因芯片研究As₂O₃作用前后NB4细胞基因表达谱的差异性,寻找As₂O₃诱导NB4细胞凋亡的相关基因并分析其可能机制。方法:流式细胞仪检测细胞凋亡率,抽提对照及诱导组细胞的mRNA,通过逆转录将As₂O₃处理前后的NB4细胞cDNA进行生物素标记,用含269个目的基因的细胞凋亡和周期基因芯片进行杂交,GEArray软件分析,筛选出As₂O₃诱导前后表达有差异的基因。芯片结果用荧光定量聚合酶链反应(realtimepolymerasechainreaction)进行验证。结果:筛选出As₂O₃作用前后表达有差异的基因共100条(占芯片基因总数的37.2%),其中97条(97/100,97%)基因表达上调,3条(3/100,3%)基因表达下调。表达上调的基因主要包括肿瘤坏死因子配体和受体家族、bcl2家族、半胱氨酸家族、DNA损伤检测和P53途径以及细胞分裂周期蛋白和激酶等基因。结论:As₂O₃主要通过上调促凋亡基因表达来诱导NB4细胞凋亡,其中TNFSF15、Apaf1、Caspase3和p16等基因可能参与As₂O₃诱导的NB4细胞凋亡,As₂O₃诱导NB4细胞凋亡的可能机制主要涉及TNF途径、线粒体途径、Caspase途径、细胞周期抑制途径和P53途径等。     

Antitumor therapeutic effects of e7 subunit and DNA vaccines in an animal cervical cancer model: antitumor efficacy of e7 therapeutic vaccines is dependent on tumor sizes, vaccine doses, and vaccine delivery routes

We previously reported that E7 subunit and DNA vaccines are both capable of inducing antitumor protection through induction of antigen-specific CTL. In this study, we investigated their ability to control established tumors according to tumor size, vaccine doses, and vaccine delivery routes. Antitumor therapeutic efficacy of both vaccine types was dependent on tumor burden. However, E7 subunit vaccines induced a higher level of antitumor therapeutic activities at the tested dose compared to DNA vaccines. This was concomitant with induction of antibody, CTL, and IFN-gamma responses, as well as histologic changes (heavy infiltration of lymphocytes and presence of apoptotic bodies). In vaccine dose titration assays, 50 and 100 microg of DNA vaccines exhibited an equivalent antitumor efficacy to 0.5 and 1 microg of E7 subunit vaccines, respectively, i.e., a 100-fold difference in E7 dosage, suggesting the importance of vaccine doses for achieving antitumor immunity. Furthermore, tumors of a larger size were controlled by intratumoral injection with E7 subunit vaccines, underscoring the importance of vaccine delivery routes for antitumor therapeutic efficacy. Thus, these data suggest that antitumor therapeutic efficacy of E7 therapeutic vaccines is determined by vaccine doses, vaccine delivery routes, and tumor sizes, and that these vaccines could be another addition to conventional therapy modalities against cervical cancer.     

Metabolic engineering of Clostridium acetobutylicum for the enhanced production of isopropanol‐butanol‐ethanol fuel mixture

Butanol is considered as a superior biofuel, which is conventionally produced by clostridial acetone‐butanol‐ethanol (ABE) fermentation. Among ABE, only butanol and ethanol can be used as fuel alternatives. Coproduction of acetone thus causes lower yield of fuel alcohols. Thus, this study aimed at developing an improved Clostridium acetobutylicum strain possessing enhanced fuel alcohol production capability. For this, we previously developed a hyper ABE producing BKM19 strain was further engineered to convert acetone into isopropanol. The BKM19 strain was transformed with the plasmid pIPA100 containing the sadh (primary/secondary alcohol dehydrogenase) and hydG (putative electron transfer protein) genes from the Clostridium beijerinckii NRRL B593 cloned under the control of the thiolase promoter. The resulting BKM19 (pIPA100) strain produced 27.9 g/l isopropanol‐butanol‐ethanol (IBE) as a fuel alcohols with negligible amount of acetone (0.4 g/l) from 97.8 g/l glucose in lab‐scale (2 l) batch fermentation. Thus, this metabolically engineered strain was able to produce 99% of total solvent produced as fuel alcohols. The scalability and stability of BKM19 (pIPA100) were evaluated at 200 l pilot‐scale fermentation, which showed that the fuel alcohol yield could be improved to 0.37 g/g as compared to 0.29 g/g obtained at lab‐scale fermentation, while attaining a similar titer. To the best of our knowledge, this is the highest titer of IBE achieved and the first report on the large scale fermentation of C. acetobutylicum for IBE production. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1083–1088, 2013     

Synthesis of biodegradable emulsifier using lipase in anhydrous pyridine

Summary Synthesis of a bioemulsifier using a lipase from Pseudomonas sp. with fructose and vinyl laurate was carried out in anhydrous pyridine. The synthetic product was identified as laurylfructose with an emulsifying activity on various hydrocarbons, edible oils and petroleum oils. The compound reduced the surface tension of distilled water from 72 mN/m to 29 mN/m and the interfacial tension of water/n-hexadecane from 50 mN/m to 6 mN/m.     

Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction

Epidemiologic and animal studies have shown that exposure to particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. Whether PM-induced lung and systemic inflammation is involved in this process is not clear. We hypothesized that PM exposure causes lung and systemic inflammation, which in turn leads to vascular endothelial dysfunction, a key step in the initiation and progression of atherosclerosis. New Zealand White rabbits were exposed for 5 days (acute, total dose 8 mg) and 4 wk (chronic, total dose 16 mg) to either PM smaller than 10 mum (PM(10)) or saline intratracheally. Lung inflammation was quantified by morphometry; systemic inflammation was assessed by white blood cell and platelet counts and serum interleukin (IL)-6, nitric oxide, and endothelin levels. Endothelial dysfunction was assessed by vascular response to acetylcholine (ACh) and sodium nitroprusside (SNP). PM(10) exposure increased lung macrophages (P<0.02), macrophages containing particles (P<0.001), and activated macrophages (P<0.006). PM(10) increased serum IL-6 levels in the first 2 wk of exposure (P<0.05) but not in weeks 3 or 4. PM(10) exposure reduced ACh-related relaxation of the carotid artery with both acute and chronic exposure, with no effect on SNP-induced vasodilatation. Serum IL-6 levels correlated with macrophages containing particles (P=0.043) and ACh-induced vasodilatation (P=0.014 at week 1, P=0.021 at week 2). Exposure to PM(10) caused lung and systemic inflammation that were both associated with vascular endothelial dysfunction. This suggests that PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.     

Immunohistochemical localization of insulin-like growth factor binding protein 2 in the central nervous system of SOD1<Superscript>G93A</Superscript> transgenic mice

In the present study, we performed immunohistochemical studies to investigate the changes of insulin-like growth factor binding protein 2 (IGFBP2) in the central nervous system of SOD1^G93A mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS). Decreased immunoreactivity for IGFBP2 was observed in the cerebral cortex, hippocampus and brainstem of SOD1^G93A transgenic mice. In the cerebral cortex, the number of IGFBP2-positive cells was decreased in the somatomotor area, somatosensory area, auditory area, visual area, entorhinal area, piriform area and prefrontal area. In the hippocampal formation, IGFBP2 immunoreactivity was significantly decreased in the CA1-3 areas and the dentate gyrus. In the brainstem, few IGFBP2-immunoreactive cells were observed in the medullary and pontine reticular formation, vestibular nucleus, trigeminal motor nucleus, facial nucleus, hypoglossal nucleus and raphe nucleus. In the spinal cord, IGFBP2 immunoreactivity was not significantly decreased in SOD1^G93A transgenic mice. This study showing decreased IGFBP2 in different brain regions of SOD1^G93A transgenic mice may provide clues for understanding differential susceptibility of neural structures in ALS. S. E. Sim and Y. H. Chung have contributed equally to this work.     

High IFN－α expression is associated with the induction of experimental autoimmune uveitis （EAU） in Fischer 344 rat

INTRODUCTIONThe CD4 T cells can be subdivided intoTh1 and Th2 subsets based on their secreted cy-tokine profile. Th1 cells characteristical1y secreteInterferonry (IFN--ry), whereas Th2 cells maiuly pro--duce IL--4[1]. IL-12 po1arizes the differentiation ofnaitre, CD4 T cells towards Th1 pathWay, in con-trast IL--4 directs T cell differentiation towards Th2pathWay The broken balance between Th1 and Th2immune responses and predominant Th1 responseare crucial factors in initiation…