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Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish 预览
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作者 Jia-He Li Zhong-Ju Shi +6 位作者 Yan Li Bin Pan Shi-Yang Yuan Lin-Lin Shi Yan Hao Fu-Jiang Cao Shi-Qing Feng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期103-111,共9页
Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord ... Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals. 展开更多
关键词 axonal REGENERATION differentially expressed GENES focal ADHESIONS Gene Ontology Kyoto Encyclopedia of GENES and Genomes neural REGENERATION protein-protein interaction network SIGNALING PATHWAY SPECTRIN tight junctions transforming growth factor beta Wnt SIGNALING PATHWAY
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Identification of protein targets for the antidepressant effects of Kai-Xin-San in Chinese medicine using isobaric tags for relative and absolute quantitation 预览
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作者 Xian-Zhe Dong Dong-Xiao Wang +3 位作者 Tian-Yi Zhang Xu Liu Ping Liu Yuan Hu 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期302-310,共9页
Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studi... Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital(approval No. X5-2016-07) on March 5, 2016. 展开更多
关键词 BRAIN-DERIVED neurotrophic factor signal pathway depression ISOBARIC tags for RELATIVE and absolute quantitation Kai-Xin-San neurogenesis protein network proteomics analysis synaptic plasticity traditional Chinese medicine
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Long-term adenosine A1 receptor activation-induced sortilin expression promotesα-synuclein upregulation in dopaminergic neurons 预览
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作者 Yun-Cheng Lv An-Bo Gao +7 位作者 Jing Yang Li-Yuan Zhong Bo Jia Shu-Hui Ouyang Le Gui Tian-Hong Peng Sha Sun Francisco S.Cayabyab 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期712-723,共12页
Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases.However,the pathogenesis underlying long-term adenosine A1 receptor... Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative diseases.However,the pathogenesis underlying long-term adenosine A1 receptor activation-induced neurodegeneration remains unclear.In this study,rats were intraperitoneally injected with 5 mg/kg of the adenosine A1 receptor agonist N6-cyclopentyladenosine(CPA)for five weeks.The mobility of rats was evaluated by forced swimming test,while their cognitive capabilities were evaluated by Y-maze test.Expression of sortilin,α-synuclein,p-JUN,and c-JUN proteins in the substantia nigra were detected by western blot analysis.In addition,immunofluorescence staining of sortilin andα-synuclein was performed to detect expression in the substantia nigra.The results showed that,compared with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine(5 mg/kg)+CPA co-treated rats,motor and memory abilities were reduced,surface expression of sortin andα-synuclein in dopaminergic neurons was reduced,and total sortilin and totalα-synuclein were increased in CPA-treated rats.MN9D cells were incubated with 500 nM CPA alone or in combination with 10μM SP600125(JNK inhibitor)for 48 hours.Quantitative real-time polymerase chain reaction analysis of sortilin andα-synuclein mRNA levels in MN9D cells revealed upregulated sortilin expression in MN9D cells cultured with CPA alone,but the combination of CPA and SP600125 could inhibit this expression.Predictions made using Jasper,PROMO,and Alibaba online databases identified a highly conserved sequence in the sortilin promoter that was predicted to bind JUN in both humans and rodents.A luciferase reporter assay of sortilin promoter plasmid-transfected HEK293T cells confirmed this prediction.After sortilin expression was inhibited by sh-SORT1,expression of p-JUN and c-JUN was detected by western blot analysis.Long-term adenosine A1 receptor activation levels upregulatedα-synuclein expression at the post-transcriptional level by affecting sort 展开更多
关键词 cognitive dysfunction DOPAMINERGIC neuron DYSKINESIA JNK/c-JUN pathway LONG-TERM adenosine A1 receptor activation neural regeneration NEURODEGENERATIVE diseases SORTILIN Α-SYNUCLEIN
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Protein microarray analysis of cytokine expression changes in distal stumps after sciatic nerve transection 预览
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作者 Xiao-Qing Cheng Xue-Zhen Liang +9 位作者 Shuai Wei Xiao Ding Gong-Hai Han Ping Liu Xun Sun Qi Quan He Tang Qing Zhao Ai-Jia Shang Jiang Peng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期503-511,共9页
A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors... A large number of chemokines,cytokines,other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration.This microenvironment is one of the major factors for regenerative success.Therefore,it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury.However,the identities of specific cytokines at various time points after sciatic nerve injury have not been determined.The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze,by protein microarray,the expression of different cytokines in the distal nerve after injury.Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines,e.g.,ciliary neurotrophic factor,were downregulated.The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines.Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways,Janus kinase/signal transducers and activators of transcription,phosphoinositide 3-kinase/protein kinase B,and notch signaling pathway.The cytokines involved in inflammation,immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes,cell-cell adhesion,and cell proliferation were up-regulated at 28 days after injury.Western blot analysis showed that the expression and changes of hepatocyte growth factor,glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis.The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration,as well as a bas 展开更多
关键词 cytokines DISTAL stump gene ontology KYOTO ENCYCLOPEDIA of Genes and Genomes pathway peripheral nerve injury protein microarray PROTEIN-PROTEIN interaction network Wallerian degeneration
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Single-nucleotide polymorphism screening and RNA sequencing of key messenger RNAs associated with neonatal hypoxic-ischemia brain damage 预览
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作者 Liu-Lin Xiong Lu-Lu Xue +7 位作者 Mohammed Al-Hawwas Jin Huang Rui-Ze Niu Ya-Xin Tan Yang Xu Ying-Ying Su Jia Liu Ting-Hua Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期86-95,共10页
A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neona... A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,Chin 展开更多
关键词 CSRNP1 DUSP5 gene ontology ANALYSIS human FETAL CORTICAL neurons LRRC25 mRNA NEONATAL HYPOXIC ischemic ENCEPHALOPATHY pathogenesis signaling pathway ANALYSIS
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Comparative proteomes change and possible role in different pathways of micro RNA-21a-5p in a mouse model of spinal cord injury 预览
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作者 Almaghalsa-Ziad Mohammed Hong-Xia Du +3 位作者 Hong-Liang Song Wei-Ming Gong Bin Ning Tang-Hong Jia 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期1102-1110,共9页
Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understo... Our previous study found that microRNA-21 a-5 p(miR-21 a-5 p)knockdown could improve the recovery of motor function after spinal cord injury in a mouse model,but the precise molecular mechanism remains poorly understood.In this study,a modified Allen's weight drop was used to establish a mouse model of spinal cord injury.A proteomics approach was used to understand the role of differential protein expression with miR-21 a-5 p knockdown,using a mouse model of spinal cord injury without gene knockout as a negative control group.We found that after introducing miR-21 a-5 p knockdown,proteins that played an essential role in the regulation of inflammatory processes,cell protection against oxidative stress,cell redox homeostasis,and cell maintenance were upregulated compared with the negative control group.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups,such as the oxidative phosphorylation pathway,which is relevant to Parkinson's disease,Huntington's disease,Alzheimer's disease,and cardiac muscle contraction.We also found that miR-21 a-5 p could be a potential biomarker for amyotrophic lateral sclerosis,as miR-21 a-5 p becomes deregulated in this pathway.These results indicate successful detection of some important proteins that play potential roles in spinal cord injury.Elucidating the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury biomarkers.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5,2014. 展开更多
关键词 BIOINFORMATICS biomarker inflammation micro RNA MITOCHONDRIA MOUSE pathway analysis PROTEOMICS spinal cord injury STATHMIN
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MicroRNA changes of bone marrow-derived mesenchymal stem cells differentiated into neuronallike cells by Schwann cell-conditioned medium 预览
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作者 Zhi-Jian Wei Bao-You Fan +9 位作者 Yang Liu Han Ding Hao-Shuai Tang Da-Yu Pan Jia-Xiao Shi Peng-Yuan Zheng Hong-Yu Shi Heng Wu Ang Li Shi-Qing Feng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第8期1462-1469,共8页
Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and ident... Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow- derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesencaymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis iden:ified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathv/ays were potentially associated with neural differentiation of b 展开更多
关键词 nerve REGENERATION MICRORNA analysis bone marrow-derived mesenchymal stem cells: Schwann CELLS neuronal-like CELLS neuronal differentiation Gene Ontology analysis Hippo SIGNALING PATHWAY Wnt SIGNALING PATHWAY transforming growth FACTOR-BETA SIGNALING PATHWAY Hedgehog SIGNALING PATHWAY neural REGENERATION
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Origin and Evolution of Core Components Responsible for Monitoring Light Environment Changes during Plant Terrestrialization
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作者 Xue Han Xin Chang +4 位作者 Zhenhua Zhang Haodong Chen Hang He Bojian Zhong Xing Wang Deng 《分子植物:英文版》 SCIE CAS CSCD 2019年第6期847-862,共16页
Light serves as the source of energy as well as an information signal for photosynthetic plants. During evolution, plants have acquired the ability to monitor environmental light radiation and adjust their development... Light serves as the source of energy as well as an information signal for photosynthetic plants. During evolution, plants have acquired the ability to monitor environmental light radiation and adjust their developmental patterns to optimally utilize light energy for photosynthesis. The mechanisms of light perception and signal transduction have been comprehensively studied in past decades, mostly in a few model plants, including Arabidopsis thaliana. However, systematic analyses of the origin and evolution of core components involved in light perception and signaling are still lacking. In this study, we took advantage of the recently sequenced genomes and transcriptomes covering all the main Archaeplastida clades in the public domain to identify orthologous genes of core components involved in light perception and signaling and to reconstruct their evolutionary history. Our analyses suggested that acclimation to different distribution of light quality in new environments led to the origination of specific light signaling pathways in plants. The UVR8 (UV Resistance Locus 8) signaling pathway originated during the movement of plants from the deeper sea to shallow water and enabled plants to deal with ultraviolet B light (UV-B). After acquisition of UV-B adaptation, origination of the phytochrome signaling pathway helped plants to colonize water surface where red light became the prominent light energy source. The seedling emergence pathway, which is mediated by a combination of light and phytohormone signals that orchestrate plant growth pattern transitions, originated before the emergence of seed plants. Although cryptochromes and some key components of E3 ubiquitin ligase systems already existed before the divergence of the plant and animal kingdoms, the coevolution and optimization of light perception and downstream signal transduction components, including key transcription factors and E3 ubiquitin ligase systems, are evident during plant terrestrialization. 展开更多
关键词 evolution UVR8 SIGNALING PATHWAY PHYTOCHROME SIGNALING PATHWAY SEEDLING emergence PATHWAY COP1/SPA complex PLANT terrestrialization
脊髓损伤后肌肉萎缩基因谱的生物信息学分析 预览 被引量:1
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作者 黄晖 王广积 《中国组织工程研究》 CAS 北大核心 2019年第27期4269-4274,共6页
背景:脊髓损伤后常伴随肌肉萎缩的发生,但是它的基本机制仍然不是十分清楚。目的:旨在探讨脊髓损伤后肌肉萎缩的分子生物学机制。方法:分析基因表达数据库中的脊髓损伤后肌肉萎缩的基因谱GSE45550。基因表达谱GSE45550包括对照组(脊髓... 背景:脊髓损伤后常伴随肌肉萎缩的发生,但是它的基本机制仍然不是十分清楚。目的:旨在探讨脊髓损伤后肌肉萎缩的分子生物学机制。方法:分析基因表达数据库中的脊髓损伤后肌肉萎缩的基因谱GSE45550。基因表达谱GSE45550包括对照组(脊髓损伤前)、实验组1(脊髓损伤后3 d)、实验组2(脊髓损伤后8 d)、实验组3(脊髓损伤后14 d)。组织为SD大鼠的比目鱼肌,每组6例。随后对4组样本数据进行差异基因分析、GO分析、通路分析。结果与结论:确定了2 513个差异表达基因,其中Wnt16、Obfc1、Ufd1l、LOC100361067、Hhatl、Fxyd1、Psmc4、Tasp1、Mettl21c、Ufd1l差异表达最显著。GO分析显示差异基因的主要生物学过程为biological_process、G蛋白偶联受体信号通路、对药物的反应、DNA依赖性转录、DNA依赖性转录的正调节、氧化还原过程、泛素依赖性蛋白分解代谢过程、凋亡过程、RNA聚合酶转录的正调控及脂肪酸β-氧化。信号通路如MAPK信号、细胞凋亡、柠檬酸循环(TCA循环)可能起到重要的作用。研究比较完整地揭示了脊髓损伤后肌肉萎缩基因谱的差异表达基因和所涉及的生物学过程和信号通路,其中Wnt16可能是脊髓损伤后肌肉萎缩中的关键基因,为未来的治疗进展提供分子靶点。 展开更多
关键词 脊髓损伤 肌肉萎缩 通路 基因 生物学过程 差异基因分析 GO分析 通路分析
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Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways 预览
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作者 Wenyan Tian Fei Teng +7 位作者 Jinping Gao Chao Gao Guoyan Liu Yanfang Zhang Shizhu Yu Wei Zhang Yingmei Wang Fengxia Xue 《癌症生物学与医学:英文版》 CAS CSCD 2019年第1期55-65,共11页
Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we i... Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways. 展开更多
关键词 ENDOMETRIAL cancer(EC) ESTROGEN INSULIN InsR-β ER-α PI3K/Akt PATHWAY MAPK/ERK PATHWAY
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Effect of CHOP siRNA on mRNA expression of PERK-ATF4-CHOP pathway in diabetic peripheral neuropathy rats
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作者 杨鑫伟 《中国医学文摘:内科学分册(英文版)》 2019年第2期86-87,共2页
Objective To investigate the effect of C/EBP homologous protein (CHOP) on mRNA expressions of RNA-dependent protein kinase-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP)... Objective To investigate the effect of C/EBP homologous protein (CHOP) on mRNA expressions of RNA-dependent protein kinase-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) pathway in diabetic peripheral neuropathy(DPN) rats. Methods 48 SD male rats werefed with high-fat diet combined with intraperitoneal injectionof streptozotocin to replicate DPN Model. Then allthe rats were divided into control group (Con),control +CHOP siRNA group ( Con + CHOPsiRNA ), Modelcontrol group (Mod) and CHOP siRNA group. Transfectionreagent and CHOP siRNA were intrathecally injected. 展开更多
关键词 CHOP SIRNA mRNA expression PERK-ATF4-CHOP PATHWAY NEUROPATHY RATS ATF SIRNA
Patrinia scabiosaefolia Inhibits Growth of 5-FU-Resistant Colorectal Carcinoma Cells via Induction of Apoptosis and Suppression of AKT Pathway
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作者 HUANG Si-zhou LIU Wang-yu +3 位作者 HUANG Yue SHEN A-ling LIU Li-ya PENG Jun 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第2期116-121,共6页
Objective: To investigate the effects of ethanol extract of Patrinia scabiosaefolia(EEPS) on chemo-resistance of colorectal cancer cells(CRC) and explore the possible molecular mechanisms. Methods: 5-fluorouracil(5-FU... Objective: To investigate the effects of ethanol extract of Patrinia scabiosaefolia(EEPS) on chemo-resistance of colorectal cancer cells(CRC) and explore the possible molecular mechanisms. Methods: 5-fluorouracil(5-FU)-resistant human colorectal carcinoma cell line(HCT-8/5-FU) and its parental cells HCT-8 were treated with EEPS(0, 0.25, 0.50, 1 or 2 mg/mL), or 5-FU(0, 100, 200, 400, 800 or 1600 μmol/L). The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay was performed to evaluate the cell viability. Cell density was observed by phase-contrast microscope, cell counting and colony formation assay were used to determine the cell proliferation of HCT-8/5-FU cells treated with 0, 0.5, 1 or 2 mg/mL EEPS. Cell apoptosis was determined by Hoechst staining. Western-blot was performed to detect the phosphorylation of AKT as well as the protein expression level of B-cell CLL/lymphoma 2(Bcl-2) and Bcl-2-associated X protein(Bax). Results: Compared with HCT-8 cells, MTT assay results indicated that HCT-8/5-FU cells were resistant to 5-FU treatment(P<0.05), and sensitive to EEPS treatment(P>0.05). Moreover, compared with untreated HCT-8/5-FU cells, 1 and 2 mg/mL of EEPS treatment significantly reduced cell density, cell number, inhibited cell survival(P<0.05), and induced apoptosis in HCT-8/5-FU cells. Furthermore, 1 and 2 mg/mL of EEPS significantly decreased the phosphorylation level of p-AKT and Bcl-2 protein expression, and increased the expression of Bax protein(P<0.05). Conclusion: EEPS is a promising therapeutic agent that may overcome chemo-resistance in cancer cells, likely through suppression of the AKT pathway and promotion of cancer cell apoptosis. 展开更多
关键词 AKT pathway COLORECTAL cancer 5-FLUOROURACIL resistance Patrinia scabiosaefolia Chinese medicine
Bioinformatics Based Therapeutic Effects of Sinomenium Acutum
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作者 LI Yu-yan ZHENG Guang LIU Liang 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第2期122-130,共9页
Objective: To decipher the possible mechanisms of Sinomenium Acutum(SA) in treating diseases by a bioinformatics method. Methods: SA ingredients were searched according to Chinese Pharmacopoeia, Chinese Medicine Dicti... Objective: To decipher the possible mechanisms of Sinomenium Acutum(SA) in treating diseases by a bioinformatics method. Methods: SA ingredients were searched according to Chinese Pharmacopoeia, Chinese Medicine Dictionary and Traditional Chinese Medicines Database(TCMD). Active compounds and target proteins of SA were acquired through the Pubchem platform. Pathway, network and function analyses of SA were performed with ingenuity pathway analysis(IPA), a bioinformatics analysis platform. Disease, biofunction-target networks were established with Cytoscape. Results: Eighteen ingredients from SA were obtained. Seven active ingredients with 31 active target proteins were acquired according to PubChem Bioassay test. By IPA analysis, 277 canonical pathways belonging to 17 function categories were collected, 23 kinds of diseases, 21 categories bio-functions were obtained. Based on P value, calculated by IPA, the top 5 significant pathway of SA targets include phosphatidylinositol 3 kinase/Akt(PI3 K/Akt) signaling, prostate cancer signaling, macrophage migration inhibitory factor(MIF) regulation of innate immunity, Guanosine-binding protein coupled receptor(GPCR) signaling, and ataxia telangiectasia mutated protein(ATM) signaling. Disease and bio-function network analysis indicated that mitogen activated protein kinase 1(MAPK1), MAPK3, p65 nuclear factor κB(RELA), nuclear factor of κB inhibitor alpha(NFκBIA), interleukin 1β(IL-1β), prostaglandin G/H synthase 2(PTGS2) and tumor protein 53(TP53) were the critical targets in various diseases treated by SA. Conclusions: In the different view of target, pathway, disease and bio-function, inflammation was found to be a central theme in many chronic conditions. SA could be used not only as an anti-inflammatory agent, but also for the treatment of cancers, neurological diseases, psychological disorders and metabolic diseases. 展开更多
关键词 Sinomenium Acutum BIOINFORMATICS ANALYSIS INGENUITY PATHWAY ANALYSIS NETWORK PHARMACOLOGY
Atsttrin reduces lipopolysaccharide-induced neuroinflammation by inhibiting the nuclear factor kappa B signaling pathway 预览
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作者 Lian Liu Yuan Qu +7 位作者 Yi Liu Hua Zhao He-Cheng Ma Ahmed Fayyaz Noor Chang-Jiao Ji Lin Nie Meng Si Lei Cheng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1994-2002,共9页
Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been show... Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). Atsttrin(2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide(10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor α 展开更多
关键词 nerve REGENERATION progranulin Atsttrin NEUROINFLAMMATION inflammatory cytokines LIPOPOLYSACCHARIDE INTRACEREBROVENTRICULAR injection ASTROCYTE nuclear factor kappa B signaling pathway progranulin knockout mouse CEREBROSPINAL fluid neural REGENERATION
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基于网络药理学的补肾益心片治疗高血压分子机制研究 预览
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作者 刘云娣 高佳珠 +4 位作者 杨智华 麦喆钘 孙治中 李俊哲 温俊茂 《中国中医药信息杂志》 CAS CSCD 2019年第8期104-109,共6页
目的采用网络药理学方法分析补肾益心片治疗高血压的作用机制,为其临床与应用提供参考。方法检索中药系统药理学数据库分析平台(TCMSP)获取补肾益心片活性成分,运用DRAR-CPI服务器、GeneCards和OMIM等数据库筛选活性成分治疗高血压的作... 目的采用网络药理学方法分析补肾益心片治疗高血压的作用机制,为其临床与应用提供参考。方法检索中药系统药理学数据库分析平台(TCMSP)获取补肾益心片活性成分,运用DRAR-CPI服务器、GeneCards和OMIM等数据库筛选活性成分治疗高血压的作用靶点。采用Cytoscape3.6.0软件构建补肾益心片活性成分-高血压靶点网络。结合String数据库和Cytoscape的NetworkAnalyzer分析蛋白相互作用关系。采用Systems Dock Web Site进行活性成分与靶点分子对接。并进行GO分析、KEGG通路富集分析。结果筛选出补肾益心片活性成分30个,作用于62个靶点,主要通过调节肾素-血管紧张素系统、Toll样受体信号通路、PI3K-AKT信号通路和Jak-STAT信号通路等发挥治疗高血压的作用。结论本研究初步揭示了补肾益心片治疗高血压的多成分、多靶点作用机制,可为后续研究提供参考。 展开更多
关键词 补肾益心片 高血压 网络药理学 靶点 通路
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校园生活垃圾分类回收和资源化利用途径 预览
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作者 何鑫 朱立杰 +2 位作者 杜洁 梁磊 柏祥 《中国环境管理干部学院学报》 CAS 2019年第5期56-58,88共4页
高校校园生活垃圾是节约型校园和“两型”社会建设必须正视的问题。不同高校间的校园生活垃圾产生量以及校园不同功能区之间在生活垃圾产量和组成上均存在有很大差异。校园生活垃圾以餐厨垃圾为主,且绝大部分为可燃物。开展校园生活垃... 高校校园生活垃圾是节约型校园和“两型”社会建设必须正视的问题。不同高校间的校园生活垃圾产生量以及校园不同功能区之间在生活垃圾产量和组成上均存在有很大差异。校园生活垃圾以餐厨垃圾为主,且绝大部分为可燃物。开展校园生活垃圾分类回收和资源化利用能够产生积极的经济效益、社会效益和生态效益,但此项工作也需要从完善法规制度、加大技术创新和加强宣传教育等方面予以推动。 展开更多
关键词 校园生活垃圾 分类回收 资源化利用 途径
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水通道蛋白AQP4对乳腺癌细胞增殖的影响及机制 预览
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作者 李英彬 孙圣荣 《现代肿瘤医学》 CAS 2019年第6期943-946,共4页
目的:研究AQP4在人乳腺癌细胞中的表达,并进一步探讨AQP4对肿瘤细胞增殖的影响及机制。方法:通过siRNA干扰技术下调乳腺癌细胞T47D和MCF-7细胞系中水通道蛋白4表达,检测这种下调对乳腺癌细胞增殖的影响并初步探讨其作用机制。结果:AQP4... 目的:研究AQP4在人乳腺癌细胞中的表达,并进一步探讨AQP4对肿瘤细胞增殖的影响及机制。方法:通过siRNA干扰技术下调乳腺癌细胞T47D和MCF-7细胞系中水通道蛋白4表达,检测这种下调对乳腺癌细胞增殖的影响并初步探讨其作用机制。结果:AQP4表达下降抑制乳腺癌细胞的增殖,可能通过ERK通路/E-钙黏蛋白实现的。结论:AQP4表达水平与乳腺癌细胞增殖正相关,相应的肿瘤抑制剂可以起到控制肿瘤生长作用。 展开更多
关键词 水通道蛋白4 小干扰RNA 增殖 通路
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Pathways of Influence of the Northern Hemisphere Mid–high Latitudes on East Asian Climate:A Review 预览
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作者 Jianping LI Fei ZHENG +2 位作者 Cheng SUN Juan FENG Jing WANG 《大气科学进展:英文版》 SCIE CAS CSCD 2019年第9期902-921,共20页
This paper reviews recent progress made by Chinese scientists on the pathways of influence of the Northern Hemisphere mid-high latitudes on East Asian climate within the framework of a“coupled oceanic-atmospheric(lan... This paper reviews recent progress made by Chinese scientists on the pathways of influence of the Northern Hemisphere mid-high latitudes on East Asian climate within the framework of a“coupled oceanic-atmospheric(land-atmospheric or seaice-atmospheric)bridge”and“chain coupled bridge”.Four major categories of pathways are concentrated upon,as follows:Pathway A—from North Atlantic to East Asia;Pathway B—from the North Pacific to East Asia;Pathway C—from the Arctic to East Asia;and Pathway D—the synergistic effects of the mid-high latitudes and tropics.In addition,definitions of the terms“combined effect”,“synergistic effect”and“antagonistic effect”of two or more factors of influence or processes and their criteria are introduced,so as to objectively investigate those effects in future research. 展开更多
关键词 East Asian climate Northern HEMISPHERE mid-high LATITUDES COUPLED oceanic-land-sea-ice-atmospheric BRIDGE chain COUPLED BRIDGE pathway synergistic effect
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表皮生长因子受体酪氨酸激酶抑制剂对大鼠尘肺纤维化干预的研究
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作者 张华 张松泉 +1 位作者 王艳 张春玲 《中华劳动卫生职业病杂志》 CAS CSCD 北大核心 2019年第6期408-415,共8页
目的观察表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)对二氧化硅(SiO2)所致大鼠肺纤维化的干预作用,探讨表皮生长因子受体(EGFR)信号通路在肺纤维化中的作用。方法SPF级健康雄性Wistar大鼠90只随机分为对照组、模型组、高剂量干预组... 目的观察表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)对二氧化硅(SiO2)所致大鼠肺纤维化的干预作用,探讨表皮生长因子受体(EGFR)信号通路在肺纤维化中的作用。方法SPF级健康雄性Wistar大鼠90只随机分为对照组、模型组、高剂量干预组、中剂量干预组和低剂量干预组,每组18 只。模型组和各剂量干预组大鼠用浓度50 mg/ml二氧化硅混悬液1 ml非气管暴露法缓慢注入气管染尘造模。对照组大鼠用同样方法注入等量灭菌生理盐水。建模后第1 天各剂量干预组大鼠用EGFR-TKIs灌胃干预,高、中、低剂量干预组分别给予EGFR-T KIs研磨粉混悬液13.59 6 75、3.375 mg/d,模型组和对照组分别给予等量生理盐水。建模后第3、 7、 14天各组分别处死6 只大鼠,HE染色观察肺组织病理学改变,Masson染色观察肺纤维化,免疫组化检测p-EGFR的表达,样本碱水解法测定肺匀浆径脯氨酸(HYP)含量,Western blot法检测肺组织肿瘤坏死因子-a(TGF-a)、 Ras磷酸化的细胞外信号调节激酶(p-Erk"2)、P[-3KCG 和蛋白激酶(Akt l)蛋白的含量。结果建模后第7、14天,HE染色和Masson染色可见大鼠肺纤维化程度随干预剂量的增加而降低,HYP 含量随干预剂量的增加而降低,差异均有统计学意义(P<0.05)。与模型组比较,各干预组肺组织TGF-a 、p-Erkl/2、 Aktl蛋白相对表达均下调,差异均有统计学意义(P <0.05),中、高剂量干预组Ras 、PI-3KCG蛋白相对表达下调,差异有统计学意义(P<0.05)。与低剂量干预组比较,中、高剂量干预组大鼠肺组织TGF-a 、Ras、 p-Erk"2蛋白相对表达下调,差异均有统计学意义(P <0.05)冲、高剂量干预组间比较,大鼠肺组织TG F-a、 Ras、 p-Erkl/2蛋白相对表达差异无统计学意义(Q0.05)。与低剂量干预组比较,高剂量干预组干预第7 、14 天大鼠肺组织PI-3KCG蛋白相对表达下调,差异有统计学意义(P<0.05 )。各剂量干预组间比较,大鼠肺组织Aktl 展开更多
关键词 表皮生长因子受体 酪氨酸酶 二氧化硅 通路 大鼠
Attenuation of lipopolysaccharide-induced neuroinflammatory events in BV-2 microglial cells by Moringa oleifera leaf extract
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作者 Gothai Sivaprakasam Palanivel Ganesan +5 位作者 Katyakyini Muniandy Shin-Young Park Duk-Yeon Cho Joon-So Kim Palanisamy Arulselvan Dong-Kug Choi 《亚太热带生物医学杂志:英文版》 CAS 2019年第3期109-115,共7页
Objective: To determine the anti-neuroinflammatory activity of Moringa oleifera leaf extract(MLE) under lipopolysaccharide stimulation of mouse murine microglia BV2 cells in vitro. Methods: The cytotoxicity effect of ... Objective: To determine the anti-neuroinflammatory activity of Moringa oleifera leaf extract(MLE) under lipopolysaccharide stimulation of mouse murine microglia BV2 cells in vitro. Methods: The cytotoxicity effect of MLE was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. The inflammatory response of BV-2 cells were induced with lipopolysaccharide. The generation of nitric oxide levels was determined by using Griess assay and the level of pro-inflammatory cytokines(IL-1β, IL-6 and TNF-α) was evaluated by ELISA kit. The expression of iNOS, COX-2 as well as IκB-ααwas carried out by immunoblot analysis. Results: MLE reduced the nitric oxide production in concentration-dependent manner, and maintained the viability of BV-2 microglial cells which indicated absence of toxicity. In addition, MLE repressed the activation of nuclear factor kappa B by arresting the deterioration of IκB-α, consequently resulted in suppression of cytokines expression such as COX-2 and iNOS. Conclusions: MLE inhibitory activities are associated with the inhibition of nuclear factor kappa B transcriptional activity in BV2 microglial cells. Thus MLE may offer a substantial treatment for neuroinflammatory diseases. 展开更多
关键词 Moringa oleifera leaf extract BV2 MICROGLIAL cells Neuro-inflammation PRO-INFLAMMATORY CYTOKINES NF-κB signaling pathway
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