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Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis
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作者 Xiao-Yan Liu Dan Qiao +5 位作者 Ya-Li Zhang Zi-Xuan Liu You-Lan Chen Ren-Ye Que Hong-Yan Cao Yan-Cheng Dai 《World Journal of Clinical Cases》 SCIE 2024年第10期1750-1765,共16页
BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylatio... BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC. 展开更多
关键词 Ulcerative colitis m6A AUTOPHAGY Characteristic genes Immune infiltration
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Effects of Chronotherapy of Benazepril on the Diurnal Profile of RAAS and Clock Genes in the Kidney of 5/6 Nephrectomy Rats 被引量:1
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作者 黄小妹 袁静萍 +3 位作者 曾星若 彭彩霞 梅啓慧 陈文莉 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2013年第3期368-374,共7页
Summary: This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wist... Summary: This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were ran- domly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastfically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angio- tensin Ⅱ (Ang Ⅱ ) and aldosterone (Aid) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmall, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no signifi- cant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Aid and RA content of a day between the MB group and EB group. The expression peak of bmall mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects. 展开更多
关键词 CHRONOTHERAPY BENAZEPRIL RAAS CIRCADIAN clock genes 5/6 subtotal nephrectomy
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来源于Alcaligenes A-6的D-氨基酰化酶基因的合成与融合表达
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作者 侯欣彤 董媛 +5 位作者 林瑞东 于梁 任媛媛 李剑光 高朝辉 滕利荣 《高等学校化学学报》 SCIE EI CAS CSCD 北大核心 2014年第8期1670-1674,共5页
将来源于Alcaligenes A-6的D-氨基酰化酶基因用大肠杆菌中的丰沛密码子替换,利用化学和基于聚合酶链反应(PCR)技术的酶促方法进行基因全合成,利用pET-32a构建重组表达载体pET-dan,转化进E.coil BL21(DE3)中进行融合表达.经SDS-PAGE电泳... 将来源于Alcaligenes A-6的D-氨基酰化酶基因用大肠杆菌中的丰沛密码子替换,利用化学和基于聚合酶链反应(PCR)技术的酶促方法进行基因全合成,利用pET-32a构建重组表达载体pET-dan,转化进E.coil BL21(DE3)中进行融合表达.经SDS-PAGE电泳、Western-blot检测和活性测定发现,D-ANase可在大肠杆菌中高效表达,目的蛋白可达到菌体总蛋白的69.2%,密码子优化后基因构建的工程菌发酵活性为96 U/mL,重组蛋白经超声细胞破碎及Ni2+柱亲和层析纯化,比活可达1692.3 U/mg,纯度可达95%以上. 展开更多
关键词 D-氨基酰化酶 产碱杆菌 基因合成 融合表达
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Ultraviolet-attenuated cercariae ofSchistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice
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作者 Meijuan Zhang Fang Tian +2 位作者 Yanan Gao Minjun Ji Guanling Wu 《The Journal of Biomedical Research》 CAS 2010年第4期277-284,共8页
Objective: To better understand the reason that Schistosoma japonicurn (S. japonicum) ultraviolet (UV)- radiated cercariae could not induce high level of protection in C57BL/6 mice. Methods: Microarray technolog... Objective: To better understand the reason that Schistosoma japonicurn (S. japonicum) ultraviolet (UV)- radiated cercariae could not induce high level of protection in C57BL/6 mice. Methods: Microarray technology was performed to investigate the gene transcription profile in skin draining lymph nodes (sdLNs) at 1 w after exposure to attenuated cercariae (AC) or normal cercariae (NC) of S. japonicum in C57BL/6 mice. The expressions of some representative genes were further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from AC-vaccinated and NC- infected mice were analyzed by real-time PCR at w 3 and 6 post-exposure. Results: The gene expressions of Th1 cytokines, including interferon-y (IFN-γ), interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in the sdLNs were significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4 and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In addition, cytotoxicity-related molecules including granzyme A, granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early stage of vaccination, and peaked at the 3rd w after vaccination with UV-AC. Conclusion: UV-AC of S. japonicum could not ef- fectively induce a Thl response in C57BL/6 mice, which may be an explanation for the low protection against parasite challenge, and the role played by up-regulated expression of cytotoxicity-related genes in mice needs to be further investigated. 展开更多
关键词 Schistosoma japonicum ultraviolet-attenuated cercariae Thl response cytotoxicity-related genes C57BL/6 mice
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A correlation study between ITGA6 gene,chromosome 8q24,MSMB genes and prostate cancer
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作者 王建业 《外科研究与新技术》 2011年第4期252-252,共1页
Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation... Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation between genotype and pheno- 展开更多
关键词 GENE A correlation study between ITGA6 gene chromosome 8q24 MSMB genes and prostate cancer
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Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells 被引量:2
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作者 Christian Hafner Stefanie Meyer +4 位作者 Ilja Hagen Bernd Becker Alexander Roesch Michael Landthaler Thomas Vogt 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第29期4511-4518,共8页
AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expressi... AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS: Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways. 展开更多
关键词 Ephrin-B IEC-6 Wound healing Gene expression C-FOS Egr-1/2 COX-2
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Effect of Exogenous p16ink4a and hRb1 Genes on Cell Cycle Regulation of Osteosarcoma Cell 被引量:1
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作者 廖翔 杨述华 +4 位作者 邵增务 李进 刘勇 熊小芊 刘心 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第6期679-682,共4页
To study the effect on regulation of cell cycle of osteosarcoma cell line MG63 tranceduced with exogenous p16ink4a and hRbl genes, pIRES-p16ink4a-hRb1, pIRES-p16ink4a and pIREShRbl plasmids were constructed by gene re... To study the effect on regulation of cell cycle of osteosarcoma cell line MG63 tranceduced with exogenous p16ink4a and hRbl genes, pIRES-p16ink4a-hRb1, pIRES-p16ink4a and pIREShRbl plasmids were constructed by gene recombination technology. The recombinant plasmid was transferred into osteosarcoma cell line MG63 by metafectene, and the resistant clones were selected by G418 selective medium, mRNA and protein expression of osteosarcoma cell line were assayed by RT-PCR and Western-Blot respectively. Cell cycle and apoptosis were analyzed by subG1 flow cytometric. Cell proliferation was tested by MTT. In the genome of these transfected target cells, the expression of p16ink4a and hRb1 mRNA and protein were detected respectively in vitro. It was demonstrated with subG1 flow cytometric analysis and MTT method that p16ink4a and hRbl genes cooperation more significantly inhibited cell growth and induced a more marked G1 arrest and apoptosis than p16ink4a/hRb1 alone (P〈0.01). Coexpression of exogenous p16ink4a with hRbl broke the regulatory feedback loop of p16ink4a-cyclinD1/CDK-hRbl and played a more significant role in inhibiting cell growth as well as inducing cell apoptosis than p16ink4a or hRbl did alone in vitro. 展开更多
关键词 pl6ink4a hRb1 Cell cycle Flow cytometric
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EFFECTS OF IFN-a COMBINED WITH IL-6 ON GROWTH AND EXPRESSION OF THE GENES RELATED TO CELL-GROWTH AND APOPTOSIS OF BONE MARROW CELLS FROM PATIENTS WITH CML
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作者 陈汉春 汤立军 +3 位作者 彭兴华 罗志勇 罗赛群 谭文斌 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2000年第3期30-34,共5页
Objective:To investigate the effects of interferon-a (IFN-a) and IFN-a combined with interleukin-6 (IL-6) on growth and expression of bcr-abl, bcl-2 and c--myc genes in the mononuclear cells (MNCs) from bone marrow (B... Objective:To investigate the effects of interferon-a (IFN-a) and IFN-a combined with interleukin-6 (IL-6) on growth and expression of bcr-abl, bcl-2 and c--myc genes in the mononuclear cells (MNCs) from bone marrow (BM) of patients with chronic myelogenous leukemia (CML). Methods: MNCs were collected from BM of the patients with CML in chronic phase by centrifugation in lymphocyte separation medium and cultured in liquid with IFN-a (200U/ml) or IFN-a (200U/ml) plus IL-6 (100 ng/ml). The growing cells were counted every day. The expression levels of b-actin, bcr-abl, bcl-2 and c-myc genes in the MNCs incubated for 24 h were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and relatively quantitative analysis of the amplified fragments by optical density scanning for the bands on gel. Results: The cell growth was markedly suppressed by IFN-a but the degree of cell-growth inhibition was slightly decreased by IL-6 on the basis of IFN-a effect. The expression of bcr-abl chimeric gene was intensely inhibited by IFN-a or IFN-a plus IL-6. The expression of bcl-2 gene was suppressed by either IFN-a or IFN-a plus IL-6, whereas that of c-myc gene was also inhibited by IFN-a but strongly elevated by IL-6 on the basis of IFN-a action. Conclusions: Both IFN-a and IFN-a plus IL-6 can inhibit the expression of anti-apoptosis gene such as bcr-abl and bcl-2 and regulate the expression of the cs.hn.cn gene related to cell proliferation and differentiation such as c-myc. Either IFN-a or IFN-a combined with IL-6 will serve as a trustful strategy of clinical treatment for CML. 展开更多
关键词 Chronic myelogenous leukemia Combination therapy Interferon-a Interleukin-6 Gene expression APOPTOSIS
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Construction and Identification of a Yeast Two-Hybrid Bait Vector and Its Effect on the Growth of Yeast Cells and the Self-Activating Function of Reporter Genes for Screening of HPV18 E6-Interacting Protein
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作者 梅泉 李双 +7 位作者 刘萍 奚玲 王世宣 孟玉菡 刘杰 杨欣慰 卢运萍 汪辉 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第1期8-12,共5页
By using a yeast two-hybrid system,a yeast two-hybrid bait vector was constructed and identified for screening of the HPV18 E6-interacting proteins,and its effects on the growth of yeast cells and the activation of re... By using a yeast two-hybrid system,a yeast two-hybrid bait vector was constructed and identified for screening of the HPV18 E6-interacting proteins,and its effects on the growth of yeast cells and the activation of reporter genes were investigated.Total mRNA extracted from Hela cells was reversely transcribed into cDNA.Fragment of HPV18 E6 cDNA was amplified using RT-PCR and directly ligated to the pGBKT7 vector.The recombinant plasmid was confirmed by restriction endonuclease analysis and DNA sequencing.Th... 展开更多
关键词 HPV18 E6 yeast two-hybrid system GENE bait plasmid
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Construction of genetically engineered macrophages expressing Smad6 and Smad7 genes with adeno-associated virus
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作者 黄云剑 赵景宏 +3 位作者 杨唐俊 范晓棠 张金海 蔡文琴 《Journal of Medical Colleges of PLA(China)》 CAS 2004年第2期71-75,80,共6页
Objective: To construct the genetically engineered macrophages expressing Smad6 and Smad7 genes with adeno-associated virus (AAV). Methods: The plasmids containing pcDNA3-Smad6/Flag and pcDNA3-Smad7/Flag were digested... Objective: To construct the genetically engineered macrophages expressing Smad6 and Smad7 genes with adeno-associated virus (AAV). Methods: The plasmids containing pcDNA3-Smad6/Flag and pcDNA3-Smad7/Flag were digested with BamHⅠ and XhoⅠ, respectively. Then the Smad6/Flag and Smad7/Flag gene segments obtained were cloned into plasmid pAAV-MCS respectively to construct the recombinant pAAV-Smad6/Flag and pAAV-Smad7/Flag plasmids. The resulting recombinant plasmids (pAAV-Smad6/Flag or pAAV-Smad7/Flag) or pAAV-LacZ plasmid were co-transfected into the HEK 293cells with pHelper and pAAV-RC by calcium-phosphate precipitation method. Recombinant AAV-2 viral particles were prepared from infected HEK293 cells and then were used to infect mouse macrophages. The expressions of Smad6 and Smad7 in macrophages were detected by immunocytochemical staining and expression of b-galactosidase was evaluated by X-gal staining. Results: The recombinant AAV vector containing Smad6 or Smad7 genes was successfully constructed. More than 95% macrophage cells expressed X-gal and Smad6 and Smad7 genes at 72 h after infection. Conclusion: These results indicate that the genetically engineered macrophages can express Smad6 and Smad7 proteins effectively, laying the foundation for the studies of TGF-β-induced diseases in vivo and highlighting the feasibility of macrophage-based gene therapy. 展开更多
关键词 macrophage SMAD6 SMAD7 adeno-associated virus vectors TGF-β gene therapy
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PIFs interact with SWI2/SNF2-related 1 complex subunit 6 to regulate H2A.Z deposition and photomorphogenesis in Arabidopsis 被引量:1
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作者 Huiru Chen Wanting Wang +9 位作者 Xiao Chen Yake Niu Yuanyuan Qi Ze Yu Minyu Xiong Pengbo Xu Wenxiu Wang Tongtong Guo Hong-Quan Yang Zhilei Mao 《Journal of Genetics and Genomics》 SCIE CSCD 2023年第12期983-992,共10页
Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to t... Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to the survival of seedlings after seeds germination. The basic-helix-loop-helix transcription factors phytochrome-interacting factors (PIFs) are the pivotal direct downstream components of phytochromes. H2A.Z is a highly conserved histone variant regulating gene transcription, and its incorporation into nucleosomes is catalyzed by SWI2/SNF2-related 1 complex, in which SWI2/SNF2-related 1 complex subunit 6 (SWC6) and actin-related protein 6 (ARP6) serve as core subunits. Here, we show that PIFs physically interact with SWC6 in vitro and in vivo, leading to the disassociation of HY5 from SWC6. SWC6 and ARP6 regulate hypocotyl elongation partly through PIFs in red light. PIFs and SWC6 coregulate the expression of auxin-responsive genes such as IAA6, IAA19, IAA20, and IAA29 and repress H2A.Z deposition at IAA6 and IAA19 in red light. Based on previous studies and our findings, we propose that PIFs inhibit photomorphogenesis, at least in part, through repression of H2A.Z deposition at auxin-responsive genes mediated by the interactions of PIFs with SWC6 and promotion of their expression in red light. 展开更多
关键词 Phytochrome-interacting factors PHOTOMORPHOgenesIS H2A.Z SWC6 Auxin-responsive genes ARABIDOPSIS
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Transcriptomic comparison to identify rapidly evolving genes in Braya humilis
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作者 YuMing Wei XiaoFei Ma PengShan Zhao 《Research in Cold and Arid Regions》 CSCD 2018年第5期428-435,共8页
The Brassicaceae species Braya humilis shows broad adaptation to different climatic zones and latitudes. However, the molecular adaptation mechanism of B. humilis is poorly understood. In China, B. humilis is mainly d... The Brassicaceae species Braya humilis shows broad adaptation to different climatic zones and latitudes. However, the molecular adaptation mechanism of B. humilis is poorly understood. In China, B. humilis is mainly distributed on the QinghaiTibetan Plateau(QTP) and in the adjacent arid region. Previous transcriptome analysis of B. humilis has revealed that 39 salt and osmotic stress response genes are subjected to purifying selection during its speciation. To further explore the adaptation mechanism of B. humilis to an arid environment, OrthoMCL program was employed in this study and 6,268 pairs of orthologous gene pairs with high confidence were obtained between B. humilis and Arabidopsis thaliana. A comparative evolutionary analysis based on nonsynonymous to synonymous substitution ratio(Ka/Ks) was then conducted. There were 64 pairs exhibiting a Ka/Ks ratio more than 0.5 and among which, three instrumental candidate genes, T20487,T22576, and T23757, were identified with strong selection signatures(Ka/Ks >1). The corresponding A. thaliana orthologs are double-stranded RNA-binding domain protein, MADS-box family protein, and NADH-dehydrogenase subunit6, which is encoded by mitochondria genome. This report not only demonstrates the adaptation contribution of fast evolving nuclear genes, but also highlights the potential adaptive value of mitochondria gene to the speciation and adaptation of B. humilis toward the extreme environment in an arid region. 展开更多
关键词 Braya humilis positive selection Ka/Ks mitochondria gene variation NADH-dehydrogenase subunit 6
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Screening key target genes for coronavirus disease 2019 based on bioinformatics and gene network
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作者 Zhi-Hua Yang Yuan-Yuan Liu +4 位作者 Hai-Feng Yan Zhao-Ge Hao-Jia Chen Lin-Wang Ting-Ting Lv 《Precision Medicine Research》 2020年第3期95-103,共9页
Objective:To use bioinformatics and gene networks to screen key target genes of coronavirus disease 2019,which provides references for clinical research and development of drugs for coronavirus disease 2019.Methods:Ta... Objective:To use bioinformatics and gene networks to screen key target genes of coronavirus disease 2019,which provides references for clinical research and development of drugs for coronavirus disease 2019.Methods:Target genes related to coronavirus disease 2019 were screened in the GeneCards and National Center for Biotechnology Information databases,and the obtained gene data were imported into the Database for Annotation,Visualization and Integrated Discovery(Version 6.8)database to collect the related information about pathways and genes.The genes enriched in the first 20 pathways and the genes whose occurrence frequency≥5 were imported into the String database respectively to construct protein-protein interaction network diagram and compare the two network diagrams.Results:TNF,IL-6,IL-2,IL-8,CXCL8,IL1B,CCL2,IFNG,STAT1,MAPK1,MAPK3,MAPK8,TP53 and RELA are ranked top in the two network diagrams,and the frequency of occurrence in the first 20 pathways was≥5.Conclusion:The incidence of coronavirus disease 2019 is associated with multiple signaling pathways,including influenza A,pathways in cancer,toll-like receptor signaling pathway,hypoxia-inducible factor-1 signaling pathway,et al.TNF,IL-6,IL-2,IL-8,CXCL8,IL1B,CCL2,IFNG,STAT1,MAPK1,MAPK3,MAPK8,TP53 and RELA are closely related to coronavirus disease 2019,which needs to be further studied.By analyzing the pathways of the genes related to coronavirus disease 2019 and the interactive network diagrams between the genes,it is helpful to understand the pathogenesis of the disease and provide a reference for clinical research and development of effective drugs for coronavirus disease 2019. 展开更多
关键词 Coronavirus disease 2019 Severe acute respiratory syndrome coronavirus 2 BIOINFORMATICS Gene network Tumor necrosis factor INTERLEUKIN-6
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Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma 被引量:2
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作者 Chang Zhang Qi Sun +14 位作者 Xu Zhang Na Qin Zhening Pu Yayun Gu Caiwang Yan Meng Zhu Juncheng Dai ChengWang Ni Li Guangfu Jin Hongxia Ma Zhibin Hu Erbao Zhang Fengwei Tan Hongbing Shen 《Cancer Communications》 SCIE 2022年第7期609-626,共18页
Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reas... Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD. 展开更多
关键词 BTG2 gene amplification KIAA1429 LUAD mRNA stability N6-methyladenosine RNA methyltransferase YTHDF2
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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis
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作者 Ruiqi Qiu Mingzhu Yang +5 位作者 Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei 《Neural Regeneration Research》 SCIE CAS 2025年第8期2408-2419,共12页
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso... Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa. 展开更多
关键词 APOPTOSIS AAV2-PDE6B ERK1/2 gene therapy PHOTOTRANSDUCTION PROTEOMICS rd10 retinitis pigmentosa
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半枝莲总黄酮对ApoE基因敲除小鼠血清PLTP、IL-6、CRP表达的影响 被引量:7
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作者 祝娉婷 卜平 +4 位作者 孙云 郑新梅 张振刚 张旭东 孙党红 《中国医科大学学报》 CAS CSCD 北大核心 2011年第5期394-396,共3页
目的探讨半枝莲总黄酮对载脂蛋白E基因敲除小鼠AS病变形成早期血脂水平与血清磷脂转运蛋白(PLTP)、Il-6、C反应蛋白(CRP)表达的影响。方法载脂蛋白E基因敲除小鼠随机分为模型组、辛伐他汀组、银杏叶胶囊组、半枝莲总黄酮高、中、低剂量... 目的探讨半枝莲总黄酮对载脂蛋白E基因敲除小鼠AS病变形成早期血脂水平与血清磷脂转运蛋白(PLTP)、Il-6、C反应蛋白(CRP)表达的影响。方法载脂蛋白E基因敲除小鼠随机分为模型组、辛伐他汀组、银杏叶胶囊组、半枝莲总黄酮高、中、低剂量组,取正常C57BL/6小鼠为对照组,各6只。除模型组、对照组给予等容量羧甲基纤维素钠外,其他各组分别给予阳性对照药与受试药8周。处死小鼠,ELISA法检测血脂、PLTP、IL-6及CRP的表达水平。取主动脉制作切片、HE染色,观察形态学变化。结果半枝莲总黄酮中、高剂量组TG、TC、LDL-C水平明显低于模型组,高剂量组HDL-C水平高于模型组,半枝莲总黄酮各组PLTP、IL-6、CPR的表达水平较模型组明显降低,有统计学意义。PLTP与IL-6水平呈正相关,与CRP水平呈正相关,IL-6与CRP水平呈正相关。结论半枝莲总黄酮可通过降低载脂蛋白E基因敲除小鼠TG、TC、LDL-C水平,升高HDL-C水平,降低PLTP、IL-6、CPR水平而发挥抗AS的作用。 展开更多
关键词 半枝莲总黄酮 载脂蛋白E基因敲除小鼠 血脂 磷脂转运蛋白 白介素6 C反应蛋白
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pl6及Ki-67蛋白在宫颈上皮内瘤变中的临床检测意义 被引量:1
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作者 邓鹏飞 左艳 +1 位作者 黎华文 郭晓红 《中国医学创新》 CAS 2013年第8期132-133,共2页
目的:探讨宫颈上皮内瘤变(cIN)中p16及Ki一67蛋白的临床表达及意义。方法:收集本院经活检或手术切除的子宫颈组织标本97例,其中宫颈正常或非特异性炎性病变17例;cINI~Ⅲ55例,宫颈鳞状细胞癌25例。对全部组织标本的p16及Ki一67... 目的:探讨宫颈上皮内瘤变(cIN)中p16及Ki一67蛋白的临床表达及意义。方法:收集本院经活检或手术切除的子宫颈组织标本97例,其中宫颈正常或非特异性炎性病变17例;cINI~Ⅲ55例,宫颈鳞状细胞癌25例。对全部组织标本的p16及Ki一67蛋白阳性表达情况进行检测。结果:cINⅡ、cINⅢ及宫颈癌之间的p16及Ki一67阳性率差异无统计学意义(P〉0.05)。而cINI、cINⅡ、cINⅢ及宫颈癌患者的阳性表达率显著高于宫颈正常或非特异性炎性病变患者(P〈O.05),且p16及Ki一67阳性表达情况呈逐渐上升趋势。结论:p16蛋白能有效的对宫颈良陛病变、cIN及宫颈癌进行鉴别诊断,并能够通过p16的染色情况对cINI和cINⅡ~Ⅲ进行鉴别,能够有效对cIN的分级情况进行判断。宫颈高度病变可以根据Ki一67蛋白的阳性表达情况与宫颈癌进行鉴别,但在与宫颈低度病变的鉴别中,还需要联合p16蛋白的阳性表达情况进行区分。 展开更多
关键词 宫颈上皮内瘤变 pl6蛋白 KI-67蛋白 检测意义
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奶牛精子变形期间Pld6基因表达及蛋白序列分析
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作者 李小俊 李欣 +3 位作者 陈晓丽 赵毅强 路永强 王栋 《畜牧兽医学报》 CAS CSCD 北大核心 2018年第12期2632-2640,共9页
本研究旨在揭示精子线粒体鞘形成机制,提高种公牛繁殖潜力。采集3头健康状况良好、15~17月龄荷斯坦公牛睾丸和附睾组织,通过冷冻切片和激光捕获显微切割(laser capture microdissection,LCM)技术获取圆形和长形精子细胞,浮游法获取附... 本研究旨在揭示精子线粒体鞘形成机制,提高种公牛繁殖潜力。采集3头健康状况良好、15~17月龄荷斯坦公牛睾丸和附睾组织,通过冷冻切片和激光捕获显微切割(laser capture microdissection,LCM)技术获取圆形和长形精子细胞,浮游法获取附睾尾精子,并采用TRizol法提取各样本RNA,对奶牛精子形成过程中的转录组进行差异分析和q PCR检测,利用生物信息学技术对其中Pld6蛋白结构和功能进行预测分析。结果表明,在精子形成过程中,Pld6基因在圆形~长形精子细胞发育过程中表达升高,而在成熟过程中转录降低甚至关闭。Pld6基因富集在线粒体融合(mitochondrial fusion)条目上,与精子尾部中段线粒体分布和形态结构相关,其蛋白为跨膜蛋白,第10~32位氨基酸是跨膜区域,三级结构呈喇叭状,在喇叭内部具有保守且呈β折叠的H(X) K(X4) D (HKD)酶活性结构域,与小鼠Pld6结构相似,且两者具有最接近的进化趋势。综上表明,根据小鼠研究推断牛精子变形过程中,Pld6基因表达增多可诱导线粒体向精子细胞尾部中段聚集,促进了线粒体鞘的正常形成,对确保牛精子活力及受精能力具有重要作用。 展开更多
关键词 精子形成 pld6基因 蛋白结构 线粒体鞘
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老年舒张性心力衰竭合并肌少症患者可溶性生长刺激表达基因2蛋白、肌红蛋白、白细胞介素-6水平与心功能的相关性
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作者 朱琪 季梅丽 庄世虹 《实用临床医药杂志》 CAS 2024年第9期57-61,共5页
目的 探讨老年舒张性心力衰竭(DHF)合并肌少症患者外周血可溶性生长刺激表达基因2蛋白(sST2)、肌红蛋白(Myo)、白细胞介素-6(IL-6)水平与心功能的相关性。方法 将122例DHF患者根据有无肌少症分为DHF合并肌少症组60例和DHF组62例,另将健... 目的 探讨老年舒张性心力衰竭(DHF)合并肌少症患者外周血可溶性生长刺激表达基因2蛋白(sST2)、肌红蛋白(Myo)、白细胞介素-6(IL-6)水平与心功能的相关性。方法 将122例DHF患者根据有无肌少症分为DHF合并肌少症组60例和DHF组62例,另将健康体检者58例、单纯肌少症患者60例分别纳入对照组、单纯肌少症组,检测各组外周血sST2、Myo、IL-6水平和心功能指标[左室射血分数(LVEF)、心排血量(CO)、心率(HR)、每搏输出量(SV)和心脏指数(CI)]。采用Pearson相关分析法分析sST2、Myo、IL-6与各心功能指标的相关性。绘制受试者工作特征(ROC)曲线,分析sST2、Myo、IL-6单独及联合诊断DHF合并肌少症的效能。结果 与对照组、单纯肌少症组相比,DHF组、DHF合并肌少症组sST2、Myo、IL-6水平和HR均升高,LVEF、CO、SV和CI均降低,差异有统计学意义(P<0.05);与DHF组相比,DHF合并肌少症组sST2、Myo、IL-6水平和HR均升高,LVEF、CO、SV和CI均降低,差异有统计学意义(P<0.05)。sST2、Myo、IL-6均分别与LVEF、CO、SV、CI呈负相关(P<0.001),均与HR呈正相关(P<0.001);sST2、Myo、IL-6、LVEF、SV是DHF合并肌少症的独立影响因素(P<0.05);sST2、Myo、IL-6联合诊断DHF合并肌少症的曲线下面积为0.936,诊断效能优于三者单独检测。结论 老年DHF合并肌少症患者外周血sST2、Myo、IL-6水平显著升高,且sST2、Myo、IL-6均与心功能指标显著相关,三者联合检测对DHF合并肌少症的诊断效能较高。 展开更多
关键词 可溶性生长刺激表达基因2蛋白 肌红蛋白 白细胞介素-6 舒张性心力衰竭 肌少症 心功能
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白介素1β及白介素6基因单核苷酸多态性与食管癌放疗后肺部感染的关联
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作者 杨静 陈璐 +2 位作者 刘燕子 祝金冉 王胜根 《西南医科大学学报》 2024年第3期236-240,250,共6页
目的分析人白介素1β(interleukin 1β,IL-1β)、白介素6(interleukin 6,IL-6)基因单核苷酸多态性与食管癌放疗后肺部感染的关联,并探讨其生理病理的调控作用。方法选取新乡医学院第三附属医院2019年1月~2022年7月收治的115例食管癌患... 目的分析人白介素1β(interleukin 1β,IL-1β)、白介素6(interleukin 6,IL-6)基因单核苷酸多态性与食管癌放疗后肺部感染的关联,并探讨其生理病理的调控作用。方法选取新乡医学院第三附属医院2019年1月~2022年7月收治的115例食管癌患者为研究对象,根据放疗后是否出现感染分为感染组(n=28)和非感染组(n=87),检测IL-1β基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点-511C/T(rs16944)、-31C/T(rs1143627)和IL-6基因单核苷酸多态性位点IL-6-572C/G(rs1800796)、IL-6-174G/C(rs1800795)的多态性,采用Spearman相关检验分析IL-1β、IL-6基因单核苷酸多态性与食管癌放疗后肺部感染的关系,多因素Logistic回归分析影响食管癌放疗后肺部感染的相关因素。结果两组患者性别、年龄、BMI、临床分期等基线资料比较,差异无统计学意义(P>0.05);放疗时间、肿瘤长度、肿瘤位置比较差异有统计学意义(P<0.05);IL-1β基因的rs16944、rs1143627位点,IL-6基因的rs1800796、rs1800795位点的基因型分布均符合Hardy-Weinberg遗传平衡定律(P>0.05);两组IL-1β基因rs16944位点基因型频率,CC、CT、TT基因型频率,C、T等位基因频率,差异均无统计学意义(P>0.05);rs1143627位点CC、CT、TT基因型频率,C、T等位基因频率差异均有统计学意义(P<0.05);IL-6基因rs1800796位点CC、CG、GG基因型频率,C、G等位基因频率差异均有统计学意义(P<0.05),rs1800795位点CC、CG、GG基因型频率,C、G等位基因频率差异均无统计学意义(P>0.05);Spearman相关检验分析显示,IL-1βrs1143627(C/T)位点、IL-6 rs1800796(C/T)位点基因多态性与食管癌放疗后肺部感染具有显著相关性(P<0.05);多因素Logistic回归分析显示,放疗时间、肿瘤长度、肿瘤位置、IL-1βrs1143627位点、IL-6 rs1800796位点单核苷酸多态性是影响食管癌患者放疗后肺部感染的多因素(P<0.05)。结论IL-1β基因rs1143627(C/T)位点多态性及IL-6基因rs1800796(C/G)位点多态性与食管癌放疗后肺部感染有关,其中rs1143627位点T等位基因、rs1800796位点G等位基因可能是易感基因。 展开更多
关键词 白介素1Β 白介素6 基因多态性 食管癌 放疗 肺部感染
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