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991.
目的 探讨沙格列汀干预非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)大鼠对肝组织腺苷酸活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)-转录因子EB(TFEB)自噬信号通路蛋白表达的影响。方法 将42只大鼠随机分为对照组、模型组和沙格列汀干预组,每组14只。采用高脂饲料喂养和链脲佐菌素腹腔注射构建NAFLD合并T2DM模型。在建模成功后,分别给予沙格列汀或生理盐水灌胃8 w。采用放射免疫法检测空腹胰岛素(INS,使用全自动生化分析仪检测空腹血糖(FPG),计算胰岛素抵抗指数(HOMA-IR)。采用Western bloting法检测肝组织p-AMPK、mTOR、TFEB和自噬标记物LC3B-II蛋白表达。结果 沙格列汀处理组大鼠体质量、肝质量和肝脏指数分别为(341.53±5.15)g、(11.06±0.49)g和(3.32±0.25)%,显著低于模型组【分别为(353.27±8.74)g、(12.77±0.84)g和(3.67±0.18)%,P<0.05】;FPG、INS和HOMA-IR水平分别为(9.45±0.71)mmol/L、(7.92±0.34)mIU/L和(3.44±0.36),显著低于模型组【分别为(13.97±0.92)mmol/L、(14.57±0.84)mIU/L和(9.03±0.91),P<0.05】;TC、TG、ALT和AST水平分别为(3.79±0.17)mmol/L、(0.81±0.13)mmol/L、(68.76±4.11)IU/L和(54.49±5.21)IU/L,均显著低于模型组【分别为(4.05±0.20)mmol/L、(2.04±0.15)mmol/L、(119.73±3.94)IU/L和(83.27±7.68)IU/L,P<0.05】;肝组织p-AMPK、TFEB和LC3B-II表达分别为(1.13±0.11)、(1.23±0.13)和(1.17±0.12),显著强于模型组【分别为(0.62±0.07)、(0.48±0.05)和(0.37±0.04)】,而mTOR表达为(0.89±0.08),显著弱于模型组【(1.53±0.16),P<0.05】。结论 沙格列汀可能通过调控AMPK/mTOR-TFEB自噬信号通路显著降低NAFLD合并T2DM大鼠血糖和血脂水平,改善肝脂肪变。 相似文献
992.
993.
精准医疗是一种基于病人特定分子标志物的医疗模式,不同于目前针对一般病人的循证医学模式。简要介绍了精准医疗的发展历史和美国的精准医疗计划,提出对制药行业的挑战主要在于:新药产品研发的复杂程度加大、较小的市场容量下研发投入难以回报、配套政策的滞后,给制药行业带来的机会在于:疾病细分导致药物创新需求增加、老药和失败药物面临重生的机遇、中小企业竞争的优势上升、延伸产业发展空间巨大,并针对性地提出了发展策略和建议。 相似文献
994.
目的:评估皮下注射低分子肝素钙对预防烧伤植皮后深静脉血栓(DVT)形成的效果。方法选取2013年1月~2014年12月本院收治的79例烧伤后需植皮的患者,其中皮下注射低分子肝素钙预DVT患者41例设为治疗组。植皮术后仅使用红外线治疗仪照射,硫酸镁热敷,活动肌肉组织等基础措施的38例为对照组。统计血浆D-二聚体(D-dimer)浓度、血小板计数、植皮成活率、创面愈合时间、感染病例数、组织器官出血病例数和DVT形成数等指标。结果治疗组术后第3、7、11、15 d的血浆D-dimer浓度均低于对照组(P<0.05);对照组的血栓形成率为10.5%,明显高于治疗组的0(P<0.05);两组术前1 d的D-dimer浓度、血小板计数,植皮成活率、创面愈合时间、感染及出血发生率差异无统计学意义(P>0.05)。结论皮下注射低分子肝素钙对预防烧伤植皮术后患者DVT形成有一定的临床意义。 相似文献
995.
996.
Qiang Du Xiaojuan Hou Lei Wang Yingqi Zhang Xinping Xi Hui Wang Mei Zhou Jinao Duan Minjie Wei Tianbao Chen Chris Shaw 《Toxins》2015,7(2):219-237
The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3''- and 5''-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation. 相似文献
997.
Naohisa Ogo Yoshinobu Ishikawa Jun-ichi Sawada Kenji Matsuno Akihiro Hashimoto Akira Asai 《ACS medicinal chemistry letters》2015,6(9):1004-1009
l-cysteine derivatives as selective KSP inhibitors. Here, we
report further optimizations using docking modeling in the L5 allosteric
binding site, which led to the discovery of several high affinity
derivatives with two fused phenyl rings in the trityl group giving
low nanomolar range KSP ATPase inhibition. The representative derivatives
potently inhibited cell growth of HCT116 cells in correlation with
KSP inhibitory activities and significantly suppressed tumor growth
in the xenograft model in vivo. 相似文献
998.
朱佳杰 《中国中西医结合消化杂志》2021,(2)
姜黄素是一种从姜科植物的根茎中提取而得的橙黄色多酚类化学物质,是中药姜黄、郁金等的主要有效成分,被广泛用于食品添加、化妆品、染料等。近些年大量研究表明姜黄素还存在较高的医疗价值,具有抗炎、抗氧化、抗肿瘤、抗凋亡、抗纤维化、免疫调节等作用,可用于多种疾病[1],已逐渐成为国内外的一个研究热点。 相似文献
999.
Synthesis and Bio‐Evaluation of New 18F‐Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice 下载免费PDF全文
Tiantian Mou Zuoquan Zhao Pu Zhang Wei Fang Cheng Peng Jie Lu Qian Wang Yunchuan Ma Xianzhong Zhang 《Chemical biology & drug design》2015,86(3):351-361
To improve the stability of 18F‐labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([18F]FPTP2, [18F]FPTP‐P2, and [18F]FPTP‐P3) were synthesized with ‘side chain’ modifications. The radiolabeled tracers and corresponding non‐radioactive compounds were obtained by substituting tosyl group with 18/19F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70–90 min with high decay‐corrected radiochemical yields (36–65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [18F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart‐to‐liver, heart‐to‐lung, and heart‐to‐blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [18F]FPTP2 suggest that the substitution of the phenyl ‘sidechain’ with other non‐phenyl rings has no effect on the myocardial targeting property of 18F‐labeled pyridaben analogs. 相似文献
1000.
Virulence‐targeted Antibacterials: Concept,Promise, and Susceptibility to Resistance Mechanisms 下载免费PDF全文
Ségolène Ruer Nikos Pinotsis David Steadman Gabriel Waksman Han Remaut 《Chemical biology & drug design》2015,86(4):379-399
In view of the relentless increase in antibiotic resistance in human pathogens, efforts are needed to safeguard our future therapeutic options against infectious diseases. In addition to regulatory changes in our antibiotic use, this will have to include the development of new therapeutic compounds. One area that has received growing attention in recent years is the possibility to treat or prevent infections by targeting the virulence mechanisms that render bacteria pathogenic. Antivirulence targets include bacterial adherence, secretion of toxic effector molecules, bacterial persistence through biofilm formation, quorum sensing and immune evasion. Effective small‐molecule compounds have already been identified that suppress such processes. In this review, we discuss the susceptibility of such compounds to the development of resistance, by comparison with known resistance mechanisms observed for classical bacteriostatic or bacteriolytic antibiotics, and by review of available experimental case studies. Unfortunately, appearance of resistance mechanisms has already been demonstrated for some, showing that the quest of new, lasting drugs remains complicated. 相似文献