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91.
Feifei Yang Peipei Shan Na Zhao Di Ge Kongkai Zhu Cheng-shi Jiang Peifeng Li Hua Zhang 《Bioorganic & medicinal chemistry letters》2019,29(1):15-21
Histone deacetylases (HDACs) has proved to be promising target for the development of antitumor drugs. In this study, we reported the design and synthesis of a class of novel hydroxamate-based bis-substituted aromatic amide HDAC inhibitors with 1,2,4-oxadiazole core. Most newly synthesized compounds displayed excellent HDAC1 inhibitory effects and significant anti-proliferative activities. Among them, compounds 11a and 11c increased acetylation of histone H3 and H4 in dose-dependent manner. Furthermore, 11a and 11c remarkably induced apoptosis in HepG2 cancer cells. Finally, the high potency of compound 11a was rationalized by molecular docking studies. 相似文献
92.
Cai Hailin Xie Pengfei Zeng Weiai Zhai Zhengguang Zhou Wen Tang Zhong 《Molecular breeding : new strategies in plant improvement》2019,39(3):1-10
Molecular Breeding - Apple mildew, caused by the fungus Podosphaera leucotricha, is an ongoing problem for apple growers in most world production regions. To manage apple foliar mildew with less... 相似文献
93.
94.
Zhang X Duan J Li K Zhou L Zhai S 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,850(1-2):348-355
A liquid chromatography-mass spectrometry method (LC-MS/MS) for the quantitative determination of rifaximin in human plasma was developed and validated. In the developed procedure, metoprolol was added to human plasma as an internal standard (IS) and acetonitrile was used to precipitate the plasma proteins before LC-MS/MS analysis. Chromatographic separation was obtained on a RESTEK Pinnacle C18 column (50 mm x 2.1mm, 5 microm) with a mobile phase consisted of ammonium acetate solution (15 mM, pH 4.32) as buffer A and methanol as mobile phase B. Quantification was performed in positive mode using multiple reaction monitoring (MRM) of the transitions m/z 786.1-->754.1 for rifaximin and m/z 268.3-->116.1 for the IS. The assay has been validated over the concentration range of 0.5-10 ng/ml (r=0.9992) based on the analysis of 0.2 ml of plasma. The assay accuracy was between 98.2% and 109%. The within-day and between-day precision was better than 3.9% and 8.9% at three concentration levels. The freeze-thaw stability was also investigated and it was found that both rifaximin and the IS were quite stable. This method provides a rapid, sensitive, specific and robust tool for the quantitative determination of rifaximin in human plasma, which is especially useful for the pharmacokinetic study of rifaximin. 相似文献
95.
Protein oxidation implicated as the primary determinant of bacterial radioresistance 总被引:1,自引:0,他引:1 下载免费PDF全文
Daly MJ Gaidamakova EK Matrosova VY Vasilenko A Zhai M Leapman RD Lai B Ravel B Li SM Kemner KM Fredrickson JK 《PLoS biology》2007,5(4):e92
In the hierarchy of cellular targets damaged by ionizing radiation (IR), classical models of radiation toxicity place DNA at the top. Yet, many prokaryotes are killed by doses of IR that cause little DNA damage. Here we have probed the nature of Mn-facilitated IR resistance in Deinococcus radiodurans, which together with other extremely IR-resistant bacteria have high intracellular Mn/Fe concentration ratios compared to IR-sensitive bacteria. For in vitro and in vivo irradiation, we demonstrate a mechanistic link between Mn(II) ions and protection of proteins from oxidative modifications that introduce carbonyl groups. Conditions that inhibited Mn accumulation or Mn redox cycling rendered D. radiodurans radiation sensitive and highly susceptible to protein oxidation. X-ray fluorescence microprobe analysis showed that Mn is globally distributed in D. radiodurans, but Fe is sequestered in a region between dividing cells. For a group of phylogenetically diverse IR-resistant and IR-sensitive wild-type bacteria, our findings support the idea that the degree of resistance is determined by the level of oxidative protein damage caused during irradiation. We present the case that protein, rather than DNA, is the principal target of the biological action of IR in sensitive bacteria, and extreme resistance in Mn-accumulating bacteria is based on protein protection. 相似文献
97.
Pan Wang Chi Tang Junjie Wu Yuefan Yang Zedong Yan Xiyu Liu Xi Shao Mingming Zhai Jie Gao Shengru Liang Erping Luo Da Jing 《Journal of cellular physiology》2019,234(7):10588-10601
Growing evidence has shown that pulsed electromagnetic fields (PEMF) can modulate bone metabolism in vivo and regulate the activities of osteoblasts and osteoclasts in vitro. Osteocytes, accounting for 95% of bone cells, act as the major mechanosensors in bone for transducing external mechanical signals and producing cytokines to regulate osteoblastic and osteoclastic activities. Targeting osteocytic signaling pathways is becoming an emerging therapeutic strategy for bone diseases. We herein systematically investigated the changes of osteocyte behaviors, functions, and its regulation on osteoclastogenesis in response to PEMF. The osteocyte-like MLO-Y4 cells were exposed to 15 Hz PEMF stimulation with different intensities (0, 5, and 30 Gauss [G]) for 2 hr. We found that the cell apoptosis and cytoskeleton organization of osteocytes were regulated by PEMF with an intensity-dependent manner. Moreover, PEMF exposure with 5 G significantly inhibited apoptosis-related gene expression and also suppressed the gene and protein expression of the receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio in MLO-Y4 cells. The formation, maturation, and osteoclastic bone-resorption capability of in vitro osteoclasts were significantly suppressed after treated with the conditioned medium from PEMF-exposed (5 G) osteocytes. Our results also revealed that the inhibition of osteoclastic formation, maturation, and bone-resorption capability induced by the conditioned medium from 5 G PEMF-exposed osteocytes was significantly attenuated after abrogating primary cilia in osteocytes using the polaris siRNA transfection. Together, our findings highlight that PEMF with 5 G can inhibit cellular apoptosis, modulate cytoskeletal distribution, and decrease RANKL/OPG expression in osteocytes, and also inhibit osteocyte-mediated osteoclastogenesis, which requires the existence of primary cilia in osteocytes. This study enriches our basic knowledge for further understanding the biological behaviors of osteocytes and is also helpful for providing a more comprehensive mechanistic understanding of the effect of electromagnetic stimulation on bone and relevant skeletal diseases (e.g., bone fracture and osteoporosis). 相似文献
98.
Wenhua Xue Zhirui Fan Lifeng Li Dan Yan Zhibo Shen Yunkai Zhai Quancheng Kan Jie Zhao 《Journal of cellular physiology》2019,234(10):18098-18110
The purpose of this study is to better understand the role of interleukin 35 (IL35) in esophageal carcinoma by comparing the mRNA level in Barrett's esophageal mucosa and in matched normal squamous mucosa and to understand how the diagnosis model works with two other genes: hepatocyte nuclear factor 1B (HNF1B) and cAMP responsive element binding protein 3-like 1 (CREB3L1). By comparing carcinoma tissue and normal tissue samples, we extracted all the differentially expressed mRNAs. The bioinformatics analysis resulted in the discovery of three prominent genes. Eventually, the three genes were utilized to train a deep-learning model. An additional wet experiment was conducted to validate the effect of IL35. All the differentially expressed genes were enriched into nine groups, each of which has specific biological functions. Given that the three significant genes HNF1B, CREB3L1, and IL35 as diagnostic features, a deep-learning model was constructed, reaching an accuracy of 93% in the training set and 87% in the test set. Our findings suggest that IL35, along with the other two signatures, can distinguish esophageal tumor samples from normal samples precisely. 相似文献
99.
Yinjun Zhang Hongyun Zhang Feifei Cheng Ying Xia Jianyong Zheng Zhao Wang 《Chirality》2019,31(11):958-967
In this study, a newly isolated strain screened from the indoxacarb‐rich agricultural soils, Bacillus cereus WZZ006, has a high stereoselectivity to racemic substrate 5‐chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester. (S)‐5‐chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester was obtained by bio‐enzymatic resolution. After the 36‐hour hydrolysis in 50‐mM racemic substrate under the optimized reaction conditions, the e.e.s was up to 93.0% and the conversion was nearly 53.0% with the E being 35.0. Therefore, B cereus WZZ006 performed high‐level ability to produce (S)‐5‐chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester. This study demonstrates a new biocatalytic process route for preparing the indoxacarb chiral intermediates and provides a theoretical basis for the application of new insecticides in agricultural production. 相似文献
100.
Yujin Ma Jingxia Shi Feifei Wang Shipeng Li Jie Wang Chaoxia Zhu Liping Li Haibo Lu Chun Li Junqiang Yan Xin Zhang Hongwei Jiang 《Journal of cellular biochemistry》2019,120(3):4044-4056
Basement membrane thickening, glomerular hypertrophy, and deposition of multiple extracellular matrix characterize the pathological basis of diabetic nephropathy (DN), a condition which ultimately leads to glomerular and renal interstitial fibrosis. Here, we identified a novel microRNA, miR-130b, and investigated its role and therapeutic efficacy in alleviating DN. Introduction of miR-130b dramatically increased cell growth and fibrosis in DN cells. We found that transforming growth factor (TGF)-β1 was a functional target of miR-130b in human glomerular mesangial cells (HMCs) and overexpression of miR-130b increased expressions of the downstream signaling molecules of TGF-β1, t-Smad2/3, p-Smad2/3, and SMAD4. An ectopic application of miR-130b increased messenger RNA and protein expressions of collagen type I (colI), colIV, and fibronectin, whose expression levels were correlated with the expression of miR-130b. Taken together, the findings of this study reveal that miR-130b in HMC cells plays an important role in fibrosis regulation and may thus be involved with the pathogenesis of DN. Therefore, miR-130b may serve as a novel therapeutic target for the prevention and the treatment of DN. 相似文献