Syntheses and antitumor activities of N′1,N′3-dialkyl-N′1,N′3-di-(alkylcarbonothioyl) malonohydrazide: The discovery of elesclomol

A series of N′¹,N′³-dialkyl-N′¹,N′³-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure–activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol.     

胎肝细胞输注与全胚注射液治疗再生障碍性贫血的机理探讨

本文对胎肝细胞输注或全胚注射液治疗再生障碍性贫血的可能机理作了一些实验性探讨。研究结果表明: 1.胎肝细胞在培养或解体过程中释放某些刺激红系造血的因子,有利于已经损伤的造血功能的恢复。 2.对正常小鼠注射无细胞胎肝制剂或全胚注射液后,骨髓红系细胞的分裂指数明显升高,骨髓中粒/红比值趋于降低,反映了骨髓中红系细胞增生活跃的状态。 3.对正常小鼠注射无细胞胎肝制剂或全胚注射液后,外周血网织红细胞和腹腔巨噬细胞的吞噬指数趋于平行增高,其增高程度和持续时间随注射次数的增加而加强。 小鼠注射无细胞胎肝制剂或全胚注射液后,巨噬细胞吞噬指数的增加,反映了巨噬细胞激活,这种作用除了提高机体的非特异性免疫功能,增强机体的抵抗力外,还可能通过巨噬细胞的活化,直接或间接地调控机体红系细胞的增殖,因而,对巨噬细胞在造血调控中的作用以及它在再生障碍性贫血发病机理研究中的意义提出了讨论。     

OmpW and OmpV are required for NaCl regulation in Photobacterium damsela

Photobacterium damsela is a marine pathogen to both fish and human beings. The bacterium can shift between the ambient seawater and hosts, suggesting the existence of proteins rapidly responding to salt concentration. In the current study, proteomic methodologies were applied to screen the outer membrane proteins (OMPs) related to salt stress. OmpW and OmpV were determined in the response in this bacterium as OmpC and OmpF did in E. coli. Furthermore, the two genes were overexpressed in E. coli Top10F and complemented in V. paraheamolyticus mutants. The ability in salt-tolerance was elevated in the E. coli overexpressed OmpW and reduced in the cells overexpressed OmpV. These V. paraheamolyticus mutants could recover their response to environmental salt concentration when they were complemented by P. damsela OmpW and OmpV. These findings indicate that OmpW and OmpV are required for environmental salt regulation in P. damsela, in which OmpW and OmpV, respectively, elevate and reduce the ability in salinity-tolerance.     

两种烟草对烟夜蛾实验种群和自然种群增长的影响

烟夜蛾对黄花烟草的产卵趋性显著高于普通烟草,为明确亲代成虫的产卵选择行为对其后代种群增长的影响,分别在室内和自然条件下,应用生命表技术测定了两种烟草对烟夜蛾的生长发育和存活、食物的转化和利用以及种群增长的影响.结果表明:(1) 室内(26±1)℃、(75±5)% R.H和16L:8D光周期条件下,与普通烟草相比,黄花烟草上幼虫的发育历期显著延长,1～3龄各期幼虫的存活率及雌蛾产卵量显著降低,种群净增殖率(R0=16.1086)和内禀增长率(rm=0.0848)减小.(2) 6龄幼虫对两种烟草的相对取食量(RCR)和近似消化率(AD)无显著差异,但是对黄花烟草的利用率(ECI)、转化率(ECD)及其相对生长率(RGR)显著下降.(3) 第二代烟夜蛾在普通烟田的种群数量呈上升趋势(I=1.0325＞1),而在黄花烟田呈下降趋势(I=0.6577＜1),第三代烟夜蛾种群在两种烟田均呈下降趋势,但普通烟田的种群增长(I=0.4571)大于黄花烟田(I=0 3592).这些结果表明,黄花烟草较不适合烟夜蛾的繁殖和种群增长,其寄主适合性不如普通烟草.     

金露梅与格桑花

青藏高原的格桑花是什么植物或者说是什么植物的花,存在广泛争议,困扰着想一探究竟的人们。格桑花作为一种精神存在于藏族百姓心中,是他们追求幸福吉祥和美好生活的情感象征,是重要的雪域文化标识,认识熟知并开发利用好它,将有助于推动藏区生态、文化和产业振兴。金露梅是青藏高原分布最广的树木,按集生羽状复叶小叶数可分为5叶金露梅和7叶金露梅,《中国植物志》对它们的记载分别是金露梅（Potentilla fruticosa L.）和小叶金露梅（P.parvifolia Fisch.）。通过对青藏高原植被和历史文化景观考察,结合当地藏民描述及地方传说,本研究认为格桑花就是金露梅,其分布海拔可以拓展到5200 m的高寒恶劣环境。金露梅生性强健,耐寒、耐旱、耐瘠薄、耐强光,象征着藏族同胞刚毅、坚强、勤劳质朴、不畏严寒、生命力顽强的品格。     

Suppression of Grb2 expression improved hepatic steatosis, oxidative stress, and apoptosis induced by palmitic acid in vitro partly through insulin signaling alteration

In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other “fatty liver” symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical “fatty liver” features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway.     

Anti-Bcl-2 family members,zfBcl-x<Subscript>L</Subscript> and zfMcl-1a,prevent cytochrome <Emphasis Type="Italic">c</Emphasis> release from cells undergoing betanodavirus-induced secondary necrotic cell death

Nervous necrosis virus (NNV)-induced, host cell apoptosis mediates secondary necrosis by an ill-understood process. In this study, redspotted grouper nervous necrosis virus (RGNNV) is shown to induce mitochondria-mediated necrotic cell death in GL-av cells (fish cells) via cytochrome c release, and anti-apoptotic proteins are shown to protect these cells from death. Western blots revealed that cytochrome c release coincided with disruption of mitochondrial ultrastructure and preceded necrosis, but did not correlate with caspases activation. To identify the mediator(s) of this necrotic process, a protein synthesis inhibitor (cycloheximide; CHX; 0.33 μg/ml) was used to block cytochrome c release as well as PS exposure and mitochondrial membrane permeability transition pore (MMP) loss. CHX (0.33 μg/ml) completely blocked viral protein B2 expression, and partly blocked protein A, protein α, and a pro-apoptotic death protein (Bad) expression. Overexpression of B2 gene increased necrotic-like cell death up to 30% at 48 h post-transfection, suggesting that newly synthesized protein (B2) may be involved in this necrotic process. Finally, necrotic death was prevented by overexpression of Bcl-2 family proteins, zfBcl-x_L and xfMcl-1a. Thus, new protein synthesis and release of cytochrome c are required for RGNNV-induced necrotic cell death, which can be blocked by anti-apoptotic Bcl-2 members. J.-L. Wu and J.-R. Hong contributed equally to the research.     

Colonic epithelium rejuvenation through YAP/TAZ

Stem cells are critical for normal tissue homeostasis and injury‐induced regeneration, but how wounding affects tissue regeneration at the cellular and molecular levels is not yet fully understood. A new study by Yui et al ( 2018 ) demonstrates that the extracellular matrix (ECM) remodeling modulates intestinal stem cells in tissue repair and regeneration via activation of the Hippo pathway effectors YAP/TAZ.     

Sodium houttuyfonate in vitro inhibits biofilm dispersion and expression of bdlA in Pseudomonas aeruginosa

Molecular Biology Reports - Biofilm dispersion is the last step in the development of biofilms, and allows bacteria to spawn novel biofilms in new locales. In the previous studies, we found that...