Equisetin Targets Intracellular Staphylococcus aureus through a Host Acting Strategy

Mammalian cells act as reservoirs of internalized bacteria to circumvent extracellular antibacterial compounds, resulting in relapse and reinfection diseases. The intracellular persistence of Staphylococcus aureus renders most traditional antibiotics useless, due to their inadequate subcellular accumulation. To replenish our antibiotic arsenal, we found that a marine-derived compound, equisetin, efficiently eliminates intracellular S. aureus by potentiating the host autophagy and inducing mitochondrial-mediated ROS generation to clear the invading S. aureus. The remarkable anti-infection activity of equisetin was validated in a peritonitis-infected mouse model. The marine product equisetin utilizes a unique dual mechanism to modulate the host–pathogen interaction in the clearance of intracellular bacteria. Thus, equisetin is an inspiring host-acting candidate for overcoming intracellular pathogens.     

肿瘤坏死因子受体相关因子基因TRAF4促进烟粉虱与共生菌Portiera的共生关系

为明确肿瘤坏死因子受体相关因子（tumor necrosis factor receptor-associated factor,TRAF）基因TRAF4在烟粉虱Bemisia tabaci隐种MEAM1与含菌细胞共生菌互作中的作用,对TRAF4蛋白进行保守结构域及系统发育分析;通过实时荧光定量PCR（quantitative real-time PCR,qPCR）方法检测TRAF4在含菌细胞和整虫体内的表达量;利用RNA干扰（RNA interference,RNAi）技术抑制烟粉虱TRAF4基因表达,然后通过qPCR技术检测含菌细胞共生菌滴度、统计烟粉虱产卵量以及采用免疫荧光技术检测烟粉虱含菌细胞的自噬水平。结果表明,TRAF4蛋白含有Zinc finger和TRAF结构域,与黑腹果蝇 Drosophila melanogaster 及埃及伊蚊 Aedes aegypti的 TRAF4 蛋白聚为一支。TRAF4在含菌细胞中显著高表达。注射dsTRAF4后,TRAF4基因表达量显著下调,Portiera滴度及烟粉虱产卵量均显著下降,含菌细胞自噬水平显著升高。表明烟粉虱TRAF4不仅影响烟粉虱的产卵量,还能通过抑制含菌细胞的自噬水平维持Portiera在烟粉虱体内的滴度,对烟粉虱与Portiera共生关系的维持起到正向调控作用。     

葡萄皮多酚调节LC3-Ⅱ表达及抑制视网膜色素上皮细胞损伤

研究葡萄皮多酚类化合物是否具有保护RPE细胞免受对脂褐素损伤的作用,并且探讨这种保护作用是否与维持自噬活性相关。脂褐素沉积是细胞衰老标志之一,当脂褐素在视网膜色素上皮细胞(RPE)中累积到一定水平,将增加年龄相关性黄斑变性(AMD)的风险。但是,脂褐素在RPE细胞内的作用机制尚不清晰。目前尚无有效预防、治疗AMD的手段,通过抗氧化剂清除自由基,维持细胞自噬活性可能会成为预防AMD的新策略。采用化学合成脂褐素主要荧光基团Nretinyledin-N-retinylethanolamin(A2E)建立RPE细胞累积脂褐素模型,用共聚焦显微镜和液相色谱-质谱联用检测A2E在RPE细胞中累积。细胞活力及凋亡检测结果表明A2E对细胞活性具有抑制作用。Western blotting结果表明A2E提高自噬相关蛋白LC3-Ⅱ的累积,并且自噬阻断剂bafilomycin A1和A2E共同处理RPE细胞条件下LC3-Ⅱ表达量较单独用A2E处理条件下没有显著性差异,说明A2E能够阻断自噬流。此外,葡萄皮提取物能够减少A2E诱导的LC3-Ⅱ累积,提示葡萄皮多酚化合物对自噬流的保护作用。并且,葡萄皮提取物能够抑制A2E诱导RPE细胞凋亡,这种抑制作用在一定程度上归因于对自噬流的保护作用。     

MAPK信号通路介导的自噬调控破骨细胞分化的研究进展

破骨细胞具有骨吸收活性,与骨组织稳态密切相关。丝裂原活化蛋白激酶(MAPK)通路是细胞介导胞内外刺激传导的信号通路,参与细胞的增殖、分化、自噬等多种生理过程。MAPK介导的自噬在调控破骨细胞分化中具有重要作用。探究MAPK的三条经典通路(ERK1/2、JNK及p38 MAPK信号通路)介导的自噬与破骨细胞分化之间的关系,对于寻找与破骨细胞相关的骨代谢疾病的新疗法具有重要意义。     

凋亡与自噬性死亡

细胞凋亡是一种由基因控制的自主性死亡过程,而自噬也被认为是非凋亡形式的程序性细胞死亡的方式。本文综述了凋亡、自噬的特征、机制及其联系。     

Blocking autophagy magnifies MK-2206-induced DNA damage in SGC-7901 cells

AIM: To investigate the effect of MK-2206, an inhibitor of protein kinase B(Akt), on the DNA damage of SGC-7901 cells.METHODS: SGC-7901 cells were treated with different concentrations of MK-2206, and phosphorylated histone H2AX(γ-H2AX) foci formation was detected by immunofluorescence staining. Western blot analysis was used to exam the levels of DNA damage-related protein. The expression of LC3-Ⅱ was determined to evaluate the change of autophagy.RESULTS: MK-2206 treatment increased the formation of γ-H2AX foci and histone H2AX phosphorylation in the SGC-7901 cells. The levels of DNA damage response protein were also increased. In addition, MK-2206-treated SGC-7901 cells increased the expression of LC3-II, a hallmark of autophagy. Inhibition of autophagy significantly enhanced MK-2206-mediated histone H2AX phosphorylation.CONCLUSION: MK-2206 induces DNA damage and autophagy in SGC-7901 cells. Blocking autophagy potentiates the response of MK-2206-induced DNA damage.     

AMPK-mTOR-ULK1-mediated autophagy protects carbon tetrachloride-induced acute hepatic failure by inhibiting p21 in rats

Autophagy is a lysosomal-dependent degradation pathway in eukaryotic cells. Recent studies have reported that autophagy can facilitate the activation of hepatic stellate cells (HSCs) and fibrogenesis of the liver during long-term carbon tetrachloride (CCl₄) exposure. However, little is known about the role of autophagy in CCl₄-induced acute hepatic failure (AHF). This study aimed to identify whether modulation of autophagy can affect CCl₄-induced AHF and evaluate the upstream signaling pathways mediated by CCl₄-induced autophagy in rats. The accumulation of specific punctate distribution of endogenous LC3-II, increased expression of LC3-II, Atg5, and Atg7 genes/proteins, and decreased expression of p62 gene were observed after acute liver injury was induced by CCl₄ in rats, indicating that CCl₄ resulted in a high level of autophagy. Moreover, loss of autophagic function by using chloroquine (CQ, an autophagic inhibitor) aggravated liver function, leading to increased expression of p21 (a cyclin-dependent kinase inhibitor) in CCl₄-treated rats. Furthermore, the AMPK-mTORC1-ULK1 axis was found to serve a function in CCl₄-induced autophagy. These results reveal that AMPK-mTORC1-ULK1 signaling-induced autophagy has a protective role in CCl₄-induced hepatotoxicity by inhibiting the p21 pathway. This study suggests a useful strategy aimed at ameliorating CCl₄-induced acute hepatotoxicity by autophagy.     

疱疹病毒ICP22蛋白研究进展

疱疹病毒(herpesvirus)是一类有囊膜结构的双链DNA病毒,典型结构由双链DNA基因组、衣壳(cap-sid)、皮层(tegument)和囊膜(envelope)组成.其家族庞大,迄今共发现了100多种,分为甲型(α)、乙型(β)、丙型(γ)疱疹病毒亚科.疱疹病毒宿主分布极其广泛,可感染两栖类、禽类、哺乳类、灵...     

Reactive Oxygen Species and Autophagy Modulation in Non-Marine Drugs and Marine Drugs

It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs.