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951.
Repression of microRNA‐382 inhibits glomerular mesangial cell proliferation and extracellular matrix accumulation via FoxO1 in mice with diabetic nephropathy 下载免费PDF全文
952.
IL‐35 recombinant protein reverses inflammatory bowel disease and psoriasis through regulation of inflammatory cytokines and immune cells 下载免费PDF全文
Yuan Wang Ying Mao Junfeng Zhang Gang Shi Lin Cheng Yi Lin Yiming Li Xiaomei Zhang Yujing Zhang Xiaolei Chen Jie Deng Xiaolan Su Lei Dai Yang Yang Shuang Zhang Dechao Yu Yuquan Wei Hongxin Deng 《Journal of cellular and molecular medicine》2018,22(2):1014-1025
Interleukin‐35 (IL‐35), a member of the IL‐12 family, functions as a new anti‐inflammatory factor involved in arthritis, psoriasis, inflammatory bowel disease (IBD) and other immune diseases. Although IL‐35 can significantly prevent the development of inflammation in many diseases, there have been no early studies accounting for the role of IL‐35 recombinant protein in IBD and psoriasis. In this study, we assessed the therapeutic potential of IL‐35 recombinant protein in three well‐known mouse models: the dextransulfate sodium (DSS)‐induced colitis mouse model, the keratin14 (K14)‐vascular endothelial growth factor A (VEGF‐A)‐transgenic (Tg) psoriasis mouse model and the imiquimod (IMQ)‐induced psoriasis mouse model. Our results indicated that IL‐35 recombinant protein can slow down the pathologic process in DSS‐induced acute colitis mouse model by decreasing the infiltrations of macrophages, CD4+T and CD8+T cells and by promoting the infiltration of Treg cells. Further analysis demonstrated that IL‐35 recombinant protein may regulate inflammation through promoting the secretion of IL‐10 and inhibiting the expression of pro‐inflammatory cytokines such as IL‐6, TNF‐α and IL‐17 in acute colitis model. In addition, lower dose of IL‐35 recombinant protein could achieve long‐term treatment effects as TNF‐α monoclonal antibody did in the psoriasis mouse. In summary, the remarkable therapeutic effects of IL‐35 recombinant protein in acute colitis and psoriasis mouse models indicated that IL‐35 recombinant protein had a variety of anti‐inflammatory effects and was expected to become an effective candidate drug for the treatment of inflammatory diseases. 相似文献
953.
Swapnil S Parhad Zhaohui Jin Jinbiao Ma William E Theurkauf ZZ Zhao Zhang Ying Huang 《EMBO reports》2018,19(7)
PIWI‐interacting RNAs (piRNAs) silence transposons in germ cells to maintain genome stability and animal fertility. Rhino, a rapidly evolving heterochromatin protein 1 (HP1) family protein, binds Deadlock in a species‐specific manner and so defines the piRNA‐producing loci in the Drosophila genome. Here, we determine the crystal structures of Rhino‐Deadlock complex in Drosophila melanogaster and simulans. In both species, one Rhino binds the N‐terminal helix–hairpin–helix motif of one Deadlock protein through a novel interface formed by the beta‐sheet in the Rhino chromoshadow domain. Disrupting the interface leads to infertility and transposon hyperactivation in flies. Our structural and functional experiments indicate that electrostatic repulsion at the interaction interface causes cross‐species incompatibility between the sibling species. By determining the molecular architecture of this piRNA‐producing machinery, we discover a novel HP1‐partner interacting mode that is crucial to piRNA biogenesis and transposon silencing. We thus explain the cross‐species incompatibility of two sibling species at the molecular level. 相似文献
954.
Genome-wide association study identified genetic variations and candidate genes for plant architecture component traits in Chinese upland cotton 总被引:1,自引:0,他引:1
Junji Su Libei Li Chi Zhang Caixiang Wang Lijiao Gu Hantao Wang Hengling Wei Qibao Liu Long Huang Shuxun Yu 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2018,131(6):1299-1314
Key message
Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton.Abstract
A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation for cultivating moderately short and compact varieties in future Chinese cotton-breeding programs.955.
Jiangying Cao Jie Zang Xiujie Kong Chunlong Zhao Ting Chen Yingying Ran Hang Dong Wenfang Xu Yingjie Zhang 《Bioorganic & medicinal chemistry》2019,27(6):978-990
Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model. 相似文献
956.
957.
Fahui Li Lihui Zhang Jinhong Feng Lei Zhang 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2017
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapeutic target for the development of cholesterol-lowering drugs. In the discovery of PCSK9/LDLR (low-density lipoprotein receptor) protein-protein interaction (PPI) impairing small molecules, a total of 47 phenylbenzo[d][1,3] dioxole-based compounds were designed and synthesised. The result revealed that the 4-chlorobenzyl substitution in the amino group is important for the PPI disrupting activity. In the hepatocyte-based functional tests, active compounds such as A12, B1, B3, B4 and B14, restored the LDLR levels on the surface of hepatic HepG2 cells and increased extracellular LDL uptake in the presence of PCSK9. It is notable that molecule B14 exhibited good performance in all the evaluations. Collectively, novel structures targeting PCSK9/LDLR PPI have been developed with hypolipidemic potential. Further structural modification of derived active compounds is promising in the discovery of lead compounds with improved activity for the treatment of hyperlipidaemia-related disorders. 相似文献
958.
Xiao Zhang Xixin He Qiuhe Chen Junfeng Lu Simona Rapposelli Rongbiao Pi 《Bioorganic & medicinal chemistry》2018,26(3):543-550
Alzheimer’s disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD. 相似文献
959.
癫痫发作敏感大鼠前深梨状皮层T区GABA免疫反应活性变化 总被引:1,自引:0,他引:1
γ-氨基丁酸(γ-aminobutyric acid,GABA)是脑内最重要的抑制性神经递质,在阻断兴奋扩布及传导中起重要作用,其参与抗癫痫作用已被证实.有研究表明:前深梨状皮层T区是颞叶癫痫的始动部位.我们从前的工作已证明:惊厥剂量的红藻氨酸(Kainic acid,A)诱发SD大鼠出现急性癫痫发作后的5~7 d,动物出现癫痫发作敏感性长期增强,而蝎毒(scorpion venom,V)可通过增强海马结构内GABA的表达,对抗其癫痫发作敏感性的形成.本研究采用免疫组化技术,并探讨其与癫痫发作敏感长期增强的可能关系,检测癫痫发作敏感大鼠和经SV处理后癫痫发作敏感性明显降低的大鼠前深梨状皮层T区的GABA免疫反应活性变化. 相似文献
960.
Zhang Hao Wang Jin-Yan Chen Yi-Juan Siemann Evan Ji Xiang-Yun Jiang Jie-Xian Wan Nian-Feng 《BioControl》2022,67(1):1-13
BioControl - The effects of plant volatiles on parasitoids are important with regards to the tri-trophic interactions among host plants, insect herbivores, and their natural enemies. However, the... 相似文献