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41.
Bin Liu Xin Zheng Jiajun Li Xiong Li Ruimei Wu Jing Yang Wei Liu Gaoping Zhao 《Bioscience reports》2021,41(1)
Objective: The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches.Materials and methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets.Results: Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways.Conclusion: The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway. 相似文献
42.
Adelson JD Barreto GE Xu L Kim T Brott BK Ouyang YB Naserke T Djurisic M Xiong X Shatz CJ Giffard RG 《Neuron》2012,73(6):1100-1107
Recovery from stroke engages mechanisms of neural plasticity. Here we examine a role for MHC class I (MHCI) H2-Kb and H2-Db, as well as PirB receptor. These molecules restrict synaptic plasticity and motor learning in the healthy brain. Stroke elevates neuronal expression not only of H2-Kb and H2-Db, but also of PirB and downstream signaling. KbDb knockout (KO) or PirB KO mice have smaller infarcts and enhanced motor recovery. KO hippocampal organotypic slices, which lack an intact peripheral immune response, have less cell death after in?vitro ischemia. In PirB KO mice, corticospinal projections from the motor cortex are enhanced, and the reactive astrocytic response is dampened after MCAO. Thus, molecules that function in the immune system act not only to limit synaptic plasticity in healthy neurons, but also to exacerbate brain injury after ischemia. These results suggest therapies for stroke by targeting MHCI and PirB. 相似文献
43.
During the development of the spinal cord, proliferative neural progenitors differentiate into postmitotic neurons with distinct fates. How cells switch from progenitor states to differentiated fates is poorly understood. To address this question, we studied the differentiation of progenitors in the zebrafish spinal cord, focusing on the differentiation of Kolmer-Agduhr″ (KA″) interneurons from lateral floor plate (LFP) progenitors. In vivo cell tracking demonstrates that KA″ cells are generated from LFP progenitors by both symmetric and asymmetric cell divisions. A photoconvertible reporter of signaling history (PHRESH) reveals distinct temporal profiles of Hh response: LFP progenitors continuously respond to Hh, while KA″ cells lose Hh response upon differentiation. Hh signaling is required in LFP progenitors for KA″ fate specification, but prolonged Hh signaling interferes with KA″ differentiation. Notch signaling acts permissively to maintain LFP progenitor cells: activation of Notch signaling prevents differentiation, whereas inhibition of Notch signaling results in differentiation of ectopic KA″ cells. These results indicate that neural progenitors depend on Notch signaling to maintain Hh responsiveness and rely on Hh signaling to induce fate identity, whereas proper differentiation depends on the attenuation of both Notch and Hh signaling. 相似文献
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James G. Burchfield Jinling Lu Daniel J. Fazakerley Shi‐Xiong Tan Yvonne Ng Katarina Mele Michael J. Buckley William E. Hughes David E. James 《Traffic (Copenhagen, Denmark)》2013,14(3):259-273
Regulated GLUT4 trafficking is a key action of insulin. Quantitative stepwise analysis of this process provides a powerful tool for pinpointing regulatory nodes that contribute to insulin regulation and insulin resistance. We describe a novel GLUT4 construct and workflow for the streamlined dissection of GLUT4 trafficking; from simple high throughput screens to high resolution analyses of individual vesicles. We reveal single cell heterogeneity in insulin action highlighting the utility of this approach – each cell displayed a unique and highly reproducible insulin response, implying that each cell is hard‐wired to produce a specific output in response to a given stimulus. These data highlight that the response of a cell population to insulin is underpinned by extensive heterogeneity at the single cell level. This heterogeneity is pre‐programmed within each cell and is not the result of intracellular stochastic events. 相似文献
46.
HBIG,无环鸟苷,干扰素联合对慢性乙型肝炎抗病毒效应观察 总被引:1,自引:0,他引:1
本文报道血清HBV复制标志阳性的慢乙肝54例,随机分为治疗组及对照组各27例进行HBIG、无环鸟苷、干扰素联合近、远期抗病毒效应观察。治疗组为无环鸟苷第一周按25~20mg/kg/d计后改17~15mg/kg/d×53天,共60天;人白细胞干扰素1×106U肌注每周3次×4周,后改1.0×106U肌注每周2次×6周,共10周;HBIG400U肌注隔日1次,共10周,对照组仅给予一般“保肝”药物。其中治疗组18例,对照组19例进行治后半年到2年追踪观察,结果近、远期HBcAg、DNAP、HBV-DNA阴转率治疗组均高于对照组,其中治疗组近、远期HBcAg,HBV-DNA阴转率均达40%以上,明显高于对照组(P<0.05~0.01),治疗组近、远期各有4例及2例HBsAg阴转,而对照组则无一例阴转,从近、远期综合抗病毒效应观察,治疗组全阴率分别为33.3%、44.4%,而对照组分别为3.79%及0%,P<0.01,治疗组无明显毒副反应。对比单用无环鸟苷,全阴率31.8%;无环鸟苷加干扰素两药联合全阴率37.5%,均有所提高,达到44.4%,值得进一步研究。 相似文献
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Qiang‐Qiang Xiong Tian‐Hua Shen Lei Zhong Chang‐Lan Zhu Xiao‐Song Peng Xiao‐Peng He Jun‐Ru Fu Lin‐Juan Ouyang Jian‐Min Bian Li‐Fang Hu Xiao‐Tang Sun Jie Xu Hui‐Ying Zhou Hao‐Hua He Xiao‐Rong Chen 《Physiologia plantarum》2019,167(4):564-584
Abrupt drought–flood alternation (T1) is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, the response mechanism of yield decline under abrupt drought–flood alternation stress at the panicle differentiation stage was analyzed by looking at the metabolome, proteome as well as yield and physiological and biochemical indexes. The results showed that drought and flood stress caused a decrease in the yield of rice at the panicle differentiation stage, and abrupt drought–flood alternation stress created a synergistic effect for the reduction of yield. The main reason for the decrease of yield per plant under abrupt drought–flood alternation was the decrease of seed setting rate. Compared with CK0 (no drought and no flood), the net photosynthetic rate and soluble sugar content of T1 decreased significantly and its hydrogen peroxidase, superoxide dismutase, peroxidase activity increased significantly. The identified differential metabolites and differentially expressed proteins indicated that photosynthesis metabolism, energy metabolism pathway and reactive oxygen species response have changed strongly under abrupt drought–flood alteration stress, which are factors that leads to the rice grain yield reduction. 相似文献
49.
Xiong Zhang Ming-You Peng En-Ming Feng Qing-Dan Li Lu Chen Hu-Cheng Yang Bing Guo Hong Liang Ying-Tong Di Lei Tang Ying Yan 《化学与生物多样性》2023,20(10):e202301061
Three previously undescribed diterpenoids, helioscopnoids A–C, and eight known compounds were isolated from the whole plants of Euphorbia helioscopia. Their structures were established by extensive analysis of spectra and data comparison with previous literatures. Among them, compound 4 was identified as 24,24-dimethoxy-25,26,27-trinoreuphan-3β-ol with revised configurations of C-13, C-14, and C-17 (13R*, 14R*, 17R*). Cytotoxicity assays revealed that all compounds exhibited varying levels of cytotoxicity against H1975 cells, with compound 9 displaying the most potent activity, as indicated by cell viability rates of 18.13 % and 20.76 % at concentrations of 20 μM and 5 μM, respectively. This study expands the understanding of E. helioscopia terpenoids’ structural diversity and biological activities, contributing to the exploration of potential therapeutic applications. 相似文献
50.
During the course of the transmissible spongiform encephalopathy diseases, a protease-resistant ordered aggregate of scrapie prion protein (PrP(Sc)) accumulates in affected animals. From mechanistic and therapeutic points of view, it is relevant to determine the extent to which PrP(Sc) formation and aggregation are reversible. PrP(Sc) solubilized with 5 m guanidine hydrochloride (GdnHCl) was unfolded to a predominantly random coil conformation. Upon dilution of GdnHCl, PrP refolded into a conformation that was high in alpha-helix as measured by CD spectroscopy, similar to the normal cellular isoform of PrP (PrP(C)). This provided evidence that PrP(Sc) can be induced to revert to a PrP(C)-like conformation with a strong denaturant. To examine the reversibility of PrP(Sc) formation and aggregation under more physiological conditions, PrP(Sc) aggregates were washed and resuspended in buffers lacking GdnHCl and monitored over time for the appearance of soluble PrP. No dissociation of PrP from the PrP(Sc) aggregates was detected in aqueous buffers at pH 6 and 7.5. The effective solubility of PrP was <0.7 nm. Treatment of PrP(Sc) with proteinase K (PK) before the analysis did not enhance the dissociation of PrP from the PrP(Sc) aggregates. Treatment with 2.5 m GdnHCl, which partially and reversibly unfolds PrP(Sc), caused only limited dissociation of PrP from the aggregates. The PrP that dissociated from the aggregates over time was entirely PK-sensitive, like PrP(C), whereas all of the aggregated PrP was partially PK-resistant. PrP also dissociated from aggregates of protease-resistant PrP generated in a cell-free conversion reaction, but only if treated with GdnHCl. Overall, the results suggest that PrP aggregation is not appreciably reversible under physiological conditions, but dissociation and refolding can be enhanced by treatments with GdnHCl. 相似文献