Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.     

Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS’s potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation.     

流感病毒的演变传播及抗病毒药物和疫苗的研究进展

流感病毒是引起人类流感的传染性病毒.1918年流感风暴席卷全球,至今仍为挥之不去的梦魇.本文综述了流感病毒的演变,在世界的传播路线和流感病毒"劫持"人体细胞的新机制,以及抗流感病毒新药和新型流感疫苗的研究进展.神经氨酸苷酶抑制剂的应用和新型流感疫苗的研制成功将为预防和治疗流感开拓广阔的前景.     

鸭梨多酚氧化酶的特性及抑制剂研究

以邻苯二酚为底物，采用分光光度法在420nm处测定鸭梨多酚氧化酶（PPO）的活性，研究了不同底物、温度、pH值和底物浓度对其活性的影响，并建立了酶促褐变反应动力学方程，探讨了柠檬酸、EDTA、亚硫酸氢钠和抗坏血酸四种抑制剂对鸭梨酶促褐变的抑制效果。结果表明，鸭梨多酚氧化酶的最适底物为邻苯二酚，最适温度为30℃，最适pH为6．6；酶促褐变反应动力学符合米氏方程所描述的单底物酶促反应动力学，以邻苯二酚为底物的动力学参数Km=0．333mol／L，Vmax=0．089U／min。相应的动力学方程为v=0．089[S]／（0．333＋[S]；四种物质对该酶均表现出不同的抑制作用，抑制效果为：抗坏血酸〉EDTA〉柠檬酸〉亚硫酸氢钠。     

The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms

Eye diseases are associated with visual impairment, reduced quality of life, and may even lead to vision loss. The efficacy of available treatment of eye diseases is not satisfactory. The unique environment of the eye related to anatomical and physiological barriers and constraints limits the bioavailability of existing agents. In turn, complex ethiopathogenesis of ocular disorders that used drugs generally are non-disease specific and do not act causally. Therefore, there is a need for the development of a new therapeutic and preventive approach. It seems that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have a significant role in the development and progression of eye diseases and could be used in the therapy of these disorders as pharmacological targets. MMPs and TIMPs play an important role in the angiogenesis, epithelial-mesenchymal transition, cell invasion, and migration, which occur in ocular diseases. In this review, we aim to describe the participation of MMPs and TIMPs in the eye diseases, such as age-related macular degeneration, cataract, diabetic retinopathy, dry eye syndrome, glaucoma, and ocular cancers, posterior capsule opacification focusing on potential mechanisms.     

魔芋葡甘聚糖颗粒阻溶剂的筛选与应用

报道三种魔芋葡甘聚糖颗粒阻溶剂的配方组成,并利用阻溶剂A进行了魔芋精粉湿法制备试验。阻溶剂A由硼酸盐──柠檬酸盐──亚硫酸盐组成,其主体成分为硼酸盐,在鲜魔芋块茎磨碎时加入磨浆机中,能有效地防止魔芋葡甘聚糖颗粒的溶胀粘连。     

豆豉功能性的研究

本文对不同品种豆豉的抗氧化、α-葡萄糖苷酶抑制和血管紧张素转换酶(ACE)抑制效果进行了比较,并对埃及曲霉纯种发酵曲中ACE抑制剂与ACE和肠胃蛋白酶预混合保温后的抑制活性进行分析,结果表明豆豉曲提取液具有较好的抗氧化和α-葡萄糖苷酶抑制效果;与ACE预混合保温后ACE抑制活性变化不大,而被不同的肠胃蛋白酶消化后抑制活性均有较大的提高,为前药型抑制剂。     

玉米秸秆稀酸预处理条件对糠醛类抑制物产生的影响

以玉米秸秆为原料,探讨稀硫酸预处理玉米秸秆过程中影响糠醛类抑制物产生的因素,运用偏相关性分析法分析不同预处理条件与还原糖、糠醛的相关性。分析得知,影响预处理液中糠醛类抑制物产生的主要因素是硫酸浓度,二者呈正相关。预处理温度和时间与糠醛浓度显著相关,而固液比对糠醛类抑制物的产生没有显著影响。实验结果表明,当硫酸浓度为1%、预处理温度120℃、时间90 min,固液比1:10时预处理液中糠醛浓度为0.99 mg/mL,还原糖浓度为27.6 mg/mL。     

Impact of γ-irradiation,CIPC treatment,and storage conditions on physicochemical and nutritional properties of potato starches

In the present study, three potato varieties were treated with chlorpropham (CIPC, 35 ppm), γ-irradiated (0.1 kGy) and stored for up to 5 months at 8 °C, and the physicochemical properties and in vitro starch digestibility of native and cooked starches were investigated. Sprouting was found to be satisfactorily suppressed by γ-irradiation and CIPC treatment. However, irradiation increased total free glucose content in two potato varieties, and decreased the thermal transition and pasting temperature of starch. The crystallinity of starch in irradiated potatoes decreased significantly (p ? 0.05) which may explain its decreased resistant starch content. Sprout inhibiting treatments and storage had no effect on in vitro starch digestibility in cooked starches, but cooling cooked starch significantly (p ? 0.05) increased its resistant starch content.