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Seong Rim Byeon Hyunjin Vincent Kim Mijin Jeon Young Gil Ahn Maeng Sup Kim Jae Yang Kong Hye Yun Kim Young Soo Kim Dong Jin Kim 《Bioorganic & medicinal chemistry letters》2013,23(11):3467-3469
Alzheimer’s disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-β. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F = 46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD50 >2000 mg/kg) and hERG channel inhibition (14% at 10 μM) results indicated safety of KMS80013. 相似文献
173.
目的研究小鼠肾缺血再灌注损伤的发病机制。方法建立小鼠肾缺血再灌注损伤模型。12只雄性C57BL/6随机分为2个组(n=6),分别为假手术组(Sham),肾缺血再灌注损伤模型组(IRI)。IRI组血管夹夹闭左肾动脉,置于32℃温箱后1h松开血管夹,去除右肾。Sham组操作同上,但不夹闭左肾动脉。再灌注24h后处死小鼠,收集血清和肾脏标本。测定血清肌酐(Cr)和血尿素氮(BUN)。PAS染色后显微镜下观察肾脏形态学变化,Western印迹分析ERK、p-ERK的表达,PCR检测MCP-1、IFN-γ。结果与假手术组(Sham)相比,IRI组血清肌酐、血尿素氮明显升高,病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显,还可观察到炎性细胞浸润明显增加。ERK、p-ERKWestern印迹结果PCR显示MCP-1、TNF-α也明显上调,但ERK表达不变。结论在肾缺血再灌注中,ERK激活介导的炎性后府可能参与了肾扣伤。 相似文献
174.
目的探讨人参皂甙Rbl(Gs—Rbl)改善阿霉素所致心力衰竭(HF)效应是否与调整蛋白激酶R样内质网激酶(PERK)通路有关。方法阿霉素(Adr)诱导的HF大鼠随机分为HF组(n=15)和Gs.Rbl组(70rng/kg/d,n=17),另随机选取同龄大鼠作为对照组(n=10)。干预结束并进行心脏超声检查后,TUNNEL检测心肌细胞凋亡率(AR),Western blot和Rt-PCR检测葡萄糖调节蛋白78(GRP78)、PERK、p-PERK、真核细胞起始因子2-(elF2a)、p-elF2a、C/EBP同源蛋白(CHOP)和cleavedcaspase-12。结果1.Adr干预成功构建HF模型,Gs—Rbl显著提高左室射血分数(LVEF)和降低心肌细胞AR(P〈O.01);2.HF组GRP78mRNA和蛋白均显著高于对照组,Gs—Rbl显著低于HF组和对照组二组的表达(P〈0.01);3.Gs—Rbl显著降低HF大鼠PERK和p-PERK表达(P〈0.01);4.HF导致elF2amRNA和蛋白、p-elF2a显著升高,Gs—Rbl显著下调三者的表达(P〈O.01);5.HF组CHOPmRNA和蛋白显著高于对照组,Gs—Rbl组显著抑制其表达(P〈0.01);6.Gs—Rbl显著抑制阿霉素所致的caspase-121TIRNA和cleaved caspase-12蛋白表达(P〈0.01)。结论Gs—Rbl通过调节PERK内质网通路介导其改善HF效应。 相似文献
175.
Nowadays, β(2)-agonists are abused illegally as "lean meat agents" for food-producing animals, and cause increasing food-safety accidents in some countries. Due to their hazard to the human health, "lean meat agents" are banned in most countries and required to be routinely monitored. We herein report a disposable electrochemiluminescent immunosensors array for near-simultaneous assay of multiple β(2)-agonist residues in swine urine, by using ractopamine and salbutamol as the models. In this investigation, a screen-printed carbon electrodes array was assembled and acted as the substrate of the immunosensors array. Then the immunosensors array was constructed by site-selectively immobilizing the antigens of ractopamine and salbutamol on the working electrodes of array. After the competitive immuno-binding, with the aid of a homemade single-pore-four-throw switch, the electrochemiluminescent signals of the two β(2)-agonists were sequentially detected using a non-array detector. The limits of detection for ractopamine and salbutamol were 8.5 and 17pg/mL, respectively, which were much lower than those of the most previous reports. Compared with other routine methods based on chromatography and ELISA, this method is more suitable for screening of multiple β(2)-agonists in quantities of samples, owing to its merits of low cost, user-friendliness and high throughput, and shows great promise in food safety and agonist surveillance. 相似文献
176.
Y Li Y Kong Z Zhou H Chen Z Wang Y-C Hsieh D Zhao X Zhi J Huang J Zhang H Li C Chen 《Cell death & disease》2013,4(11):e935
Apoptosis resistance is a hurdle for cancer treatment. HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 depletion can sensitize cancer cells to extrinsic apoptotic stimuli. In addition, HECTD3 inhibits TNF-related apoptosis-inducing ligand (TRAIL)-induced caspase-8 cleavage in an E3 ligase activity-dependent manner. Mutation of the caspase-8 ubiquitination site at K215 abolishes the HECTD3 protection from TRAIL-induced cleavage. Finally, HECTD3 is frequently overexpressed in breast carcinomas. These findings suggest that caspase-8 ubiquitination by HECTD3 confers cancer cell survival. 相似文献
177.
Jie Xu Xiaolin Zhou Jilin Wang Zhaoli Li Xuan Kong Jin Qian Ye Hu Jing-Yuan Fang 《Cell reports》2013,3(5):1526-1538
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178.
179.
Po-Han Chan Bhaswati Ghosh Hong-Zheng Lai Hwei-Ling Peng Kwok Kong Tony Mong Yu-Chie Chen 《PloS one》2013,8(3)
Glycan-bound nanoprobes have been demonstrated as suitable sensing probes for bacteria containing glycan binding sites. In this study, we demonstrated a facile approach for generating glycan-bound gold nanoclusters (AuNCs). The generated AuNCs were used as sensing probes for corresponding target bacteria. Mannose-capped AuNCs (AuNCs@Mann) were generated and used as the model sensors for target bacteria. A one-step synthesis approach was employed to generate AuNCs@Mann. In this approach, an aqueous solution of tetrachloroauric acid and mannoside that functionized with a thiol group (Mann-SH) was stirred at room temperature for 48 h. The mannoside functions as reducing and capping agent. The size of the generated AuNCs@Mann is 1.95±0.27 nm, whereas the AuNCs with red photoluminescence have a maximum emission wavelength of ∼630 nm (λexcitation = 375 nm). The synthesis of the AuNCs@Mann was accelerated by microwave heating, which enabled the synthesis of the AuNCs@Mann to complete within 1 h. The generated AuNCs@Mann are capable of selectively binding to the urinary tract infection isolate Escherichia coli J96 containing the mannose binding protein FimH expressed on the type 1 pili. On the basis of the naked eye observation, the limit of detection of the sensing approach is as low as ∼2×106 cells/mL. 相似文献
180.
Dong Zheng Qiang Sun Zhaoliang Su Fanzhi Kong Xiaoju Shi Jia Tong Pei Shen Tianqing Peng Shengjun Wang Huaxi Xu 《PloS one》2013,8(4)
The outer membrane protein RagB is one of the major virulence factors of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis). In order to induce protective immune response against P. gingivalis infection, an mGITRL gene-linked ragB DNA vaccine (pIRES-ragB-mGITRL ) was constructed. Six-week-old female BALB/c mice were immunized with pIRES-ragB-mGITRL through intramuscular injection and then challenged by subcutaneous injection in the abdomen with P. gingivalis. RagB-specific antibody-forming cells were evaluated by an Enzyme-linked immunosorbent spot, and specific antibody was determined by enzyme-linked immunosorbent assay. In addition, the frequencies of Tfh and IFN-γ+ T cells in spleen were measured using flow cytometer, and the levels of IL-21 and IFN-γ mRNA or proteins were detected by real time RT-PCR or ELISA. The data showed that the mGITRL-linked ragB DNA vaccine induced higher levels of RagB-specific IgG in serum and RagB-specific antibody-forming cells in spleen. The frequencies of Tfh and IFN-γ+ T cells were obviously expanded in mice immunized by pIRES-ragB-mGITRL compared with other groups (pIRES or pIRES-ragB ). The levels of Tfh and IFN-γ+ T cells associated cytokines were also significantly increased in pIRES-ragB-mGITRL group. Therefore, the mice immunized with ragB plus mGITRL showed the stronger resistant to P. gingivalis infection and a significant reduction of the lesion size caused by P. gingivalis infection comparing with other groups. Taken together, our findings demonstrated that intramuscular injection of DNA vaccine ragB together with mGITRL induced protective immune response dramatically by increasing Tfh and IFN-γ+ T cells and antibody production to P. gingivalis. 相似文献