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Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model
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作者 Wei Wang Jing Wang +2 位作者 Xiu-Xiu Ren Hai-Long Yue Zheng Li 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第11期4468-4476,共9页
BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mai... BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins. 展开更多
关键词 Colon cancer Invigorating-spleen and anticancer formula extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway Mice model C-MYC
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Pterygium epithelium abnormal differentiation related to activation of extracellular signal-regulated kinase signaling pathway in vitro 被引量:5
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作者 Juan Peng Xiang-Yin Sha +2 位作者 Yi Liu Rui-Ming Yang Ye Wen 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2015年第6期1118-1125,共8页
AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylate... AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation. 展开更多
关键词 abnormal differentiation epithelial cells PTERYGIUM extracellular signal-regulated kinase signaling pathway in vitro
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Expression of Extracellular Signal-regulated Kinase and Angiotensin-converting Enzyme in Human Atria during Atrial Fibrillation 被引量:1
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作者 戴友平 王祥 +2 位作者 曹林生 杨杪 邬堂春 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2004年第1期32-36,共5页
In order to investigate the changes in the expression of extracellular signal regulated kinase (ERK1/ERK2) and angiotensin converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheu... In order to investigate the changes in the expression of extracellular signal regulated kinase (ERK1/ERK2) and angiotensin converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF≥6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2 mRNA was increased in the patients with CAF (74±19 U vs sinus rhythm: 32±24 U, P <0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150 % in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF. 展开更多
关键词 atrial fibrillation angiotensin converting enzyme extracellular signal regulated kinase
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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3βSignaling Pathway
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作者 JIANG Yu-xia ZHAO Yan-na +1 位作者 YU Xiao-ling YIN Li-ming 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2024年第7期588-599,共12页
Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell differentiation.Methods AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg... Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell differentiation.Methods AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow cytometry.Cell morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,respectively.The protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3β),GSK3βand signal transducer and activator of transcription 1(STAT1)were detected by Western blot.Thirty-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were recorded.Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining.WT1 and GATA-1 expressions were detected by immunohistochemical staining.Results The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(p<0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(p<0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3βand STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P<0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P<0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor tissues(P<0.05 or P<0.01).Conclusion GRd might induce the differentiation of AML cells via regulating the ERK/GSK-3βsignaling pathway. 展开更多
关键词 ginsenoside Rd myeloid leukemia survival DIFFERENTIATION extracellular signal-related kinase signaling pathway
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Regulation of the EGFR pathway by visfatin and its effect on cardiac hypertrophy
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作者 Liang Chang Lu Xu +2 位作者 Yan Jia Su-Yun Liu Yong-Jun Li 《Journal of Hainan Medical University》 2021年第3期7-11,共5页
Objective:To investigate the regulation of the epidermal growth factor receptor(EGFR)pathway by visfatin and its effect on cardiac hypertrophy.Methods:60 Wistar male rats were randomly divided into control group,visfa... Objective:To investigate the regulation of the epidermal growth factor receptor(EGFR)pathway by visfatin and its effect on cardiac hypertrophy.Methods:60 Wistar male rats were randomly divided into control group,visfatin group and visfatin+AG1478 group,with 20 rats in each group.The cardiac mass index,left ventricular mass index and cardiomyocyte volume of rats in each group were calculated.The total protein content of each group of cardiomyocytes was detected by coomassie bright blue staining,and the protein expression was detected by Western blotting.Results:Compared with the control group,the cardiac mass index,left ventricular mass index,cardiomyocyte volume,protein content,and relative expressions of ANP and BNP were significantly increased in the visfatin group(P<0.05).The relative expression levels of EGFR,p-AKT,p-ERK1/2,p-STAT3,ANP and BNP in cardiac myocytes in the visfatin group were significantly higher than those in the control group and the visfatin+AG1478 group(P<0.05).Conclusion:Visfatin induces hypertrophy in cardiomyocytes by activating the EGFR signaling pathway. 展开更多
关键词 VISFATIN Epidermal growth factor receptor signaling pathway Cardiomyocyte hypertrophy extracellular signaling kinase Signal transduction and transcription activator 3 Serine threonine kinase
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Study on Effects of Extracts from Salvia Miltiorrhiza and Curcuma Longa in Inhibiting Phosphorylated Extracellular Signal Regulated Kinase Expression in Rat's Hepatic Stellate Cells 被引量:34
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作者 成扬 平键 +2 位作者 刘成 谭英姿 陈高峰 《Chinese Journal of Integrative Medicine》 SCIE CAS 2006年第3期207-211,共5页
Objective: To study the effect of salvianolic acid B (SAB) and curcumin, the extracts of Solvie Miltiorrhize and Curcume Longe, on the proliferation and activation of hepatic stellate cell (HSC), and the extracel... Objective: To study the effect of salvianolic acid B (SAB) and curcumin, the extracts of Solvie Miltiorrhize and Curcume Longe, on the proliferation and activation of hepatic stellate cell (HSC), and the extracellular signal regulated kinase (ERK) expression in it. Methods: Rat's HSC-T6 were cultured and treated by SAB or curcumin. The inhibitory effect on cell proliferation was determined by 3-(4,5-dimthyl-2- 2thiazoly)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and the expression levels of a smooth actin (a-SMA), collagen type Ⅰ , and ERK were determined by Western blot. Results: SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of a-SMA ( P〈0.01 ). Curcumin significantly reduced the expression of collagen type Ⅰ (P〈0.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group ( P〈0.01 and P〈0.05 respectively). Conclusion: SAB and curcumin could significantly inhibit the proliferation, activation of HSC, and the production of type Ⅰ collagen in HSC, the mechanism may be associated with their inhibition on ERK phosphorylation. 展开更多
关键词 salvianolic acid B CURCUMIN extracellular signal regulated kinase PHOSPHORYLATION
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TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies 被引量:9
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作者 Bruno Christian Koehler Toni Urbanik +5 位作者 Binje Vick Regina Johanna Boger Steffen Heeger Peter R Galle Marcus Schuchmann Henning Schulze-Bergkamen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第47期5924-5935,共12页
AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resis... AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC. 展开更多
关键词 Hepatocellular carcinoma APOPTOSIS Tumor necrosis factor-related apoptosis inducing ligand BCL-XL MCL-1 5-FLUOROURACIL Doxorubicin SORAFENIB Phosphoinositol-3-kinase (Mitogen-activated protein kinase)/(extracellular signal regulated kinase kinase c-Jun N-terminal kinase
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Shenmai Injection(参麦注射液) Inhibiting the Extracellular Signal Regulated Kinase-lnduced Human Airway Smooth Muscle Proliferation in Asthma 被引量:6
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作者 赵丽敏 马利军 +1 位作者 张罗献 吴纪珍 《Chinese Journal of Integrative Medicine》 SCIE CAS 2010年第4期331-336,共6页
Objective: To investigate the relationship between the proliferation of sensitized human airway smooth muscle cells (HASMCs) and the expression of extracellular signal regulated kinase (ERK) and the effect of She... Objective: To investigate the relationship between the proliferation of sensitized human airway smooth muscle cells (HASMCs) and the expression of extracellular signal regulated kinase (ERK) and the effect of Shenmai Injection (参麦注射液, SMI) on HASMCs. Methods: The HASMCs cultured in vitro were divided into three groups: (1) control group; (2) sensitized group: containing 10% asthmatic serum; (3) SMI group: further divided into three different concentration subgroups interferred with 10 μL/mL, 50 μL/mL, and 100 μL/mL SMI, respectively. The proliferation of HASMCs was detected using MTT method, the expression of proliferating cell nucleus antigen (PCNA) in HASMCs was detected using immunocytochemical staining, and the expression of phosphoration-ERK1/2 (p-ERK1/2) protein was detected using Western-blot. Results: After passive sensitization, the optical density value (A49o value) of HASMCs was significantly increased from 0.366± 0.086 to 0.839 ± 0.168 (P〈0.05). In addition, the expression of PCNA was significantly increased from 28.7% ± 5.9% in the control group to 69.8% ±7.5% in the sensitized group (P〈0.05). At the same time, the expression of p-ERK1/2 in passively sensitized HASMCs was significantly increased compared with the control group (all P〈0.05). Affer application of 10 μL/mL, 50 μL/mL, and 100 μL/mL SMI to the cultured media of passively sensitized group, the A570 value was significantly decreased from 0.839 ±0.168 to 0.612 ±0.100, 0.412 ± 0.092, and 0.339 ± 0.077, respectively (P〈0.05). Moreover, the expression of PCNA was significantly decreased from 69.8% ±7.5% to 57.8% ± 6.2%, 40.7%±5.4%, and 26.1% ± 5.2%, respectively. At the same time, the expression of p-ERK1/2 in each SMI group was significantly decreased compared with the sensitized group (all ,P〈0.05). Conclusion: ERK signal transduction pathway may be involved in the airway remodeling in asthma. The expression of ERK can be inhibited by SMI in a dose-dependent manner, thus preventing the proliferation of HASMCs. 展开更多
关键词 Shenmai Injection airway smooth muscle cells extracellular signal regulated kinase airway remodeling
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Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia 被引量:3
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作者 ZHANG Ying YE Li-ping WANG Biao CAO Shi-cheng SUN Li-guang 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2007年第6期422-427,共6页
Objective: To observe the effects of lead on levels ofphosphorylated extracellular signal regulated kinase (p-ERK) in the cytoplasm of primary cultures of rat astroglial cells and the possible protective effect of ... Objective: To observe the effects of lead on levels ofphosphorylated extracellular signal regulated kinase (p-ERK) in the cytoplasm of primary cultures of rat astroglial cells and the possible protective effect of basic fibroblast growth factor (bFGF) on lead-induced effects. Methods: The primary astroglia cells from 1-6 d old Wistar rats were cultured. The cells pretreated with the MEK1 (mitogen-activated protein kinase kinase 1) inhibitor PD98059 and bFGF, respectively, were exposed to Pb acetate of different concentrations for different times. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) methods were used to detect the protein and mRNA expressions of ERK. Results: mRNA expression for ERK peaked 15 min after initiation of lead exposure (P〈0.05) and protein expression of p-ERK peaked at 30 min (P〈0.05). ERK mRNA levels and p-ERK protein levels returned to baseline after 60 and 120 min of lead exposure, respectively (P〉0.05). The increase in p-ERK levels in lead-treated cells could be inhibited by PD098059. Activation of ERK in the cells by lead was prevented by pretreatment with bFGF. Total ERK protein levels did not change under the same experimental conditions (P〉0.05). Conclusion: Low-level lead exposure resulted in transient activation of ERK through the MEK pathway, which then returned to basal levels in the continued presence of lead. Exogenous bFGF protected ERK signaling components in astroglia from lead poisoning. 展开更多
关键词 LEAD ASTROGLIA extracellular signal regulated kinase (ERK) Basic fibroblast growth factor (bFGF)
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Identification of key genes involved in axon regeneration and Wallerian degeneration by weighted gene co-expression network analysis 被引量:4
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作者 Yan Lu Qi Shan +4 位作者 Mei Ling Xi-An Ni Su-Su Mao Bin Yu Qian-Qian Cao 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第4期911-919,共9页
Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair perip... Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system.In this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury.We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,respectively.Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted neurodegeneration.Next,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve segments.In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway.Collectively,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration.All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021. 展开更多
关键词 axon regeneration extracellular signal-regulated kinase signaling pathway hub genes Kif22 peripheral nerve injury protein kinase Schwann cells Wallerian degeneration weighted gene co-expression network analysis
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Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3 被引量:18
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作者 Fang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian ZhouFang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian Zhou, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai 200032, China Author contributions: Gu FM, Li QL and Gao Q contributed equally to this work Gu FM and Li QL performed the experi- ments and interpretation of the data and statistical analysis +3 位作者 Zhou J and Gao Q contributed to the conception and design of the study Gu FM, Gao Q, Li QL and Zhou J wrote the manuscript Jiang JH, Huang XY, Pan JF and Fan J made substantial contri- bution to the design and conception of the study and interpreta- tion of data all authors read and approved the f inal manuscript. 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第34期3922-3932,共11页
AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).METHODS: Human and rat HCC ce... AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model.RESULTS: Sorafenib decreased STAT3 phosphorylationat the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phosphatase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib signifi cantly inhibited STAT3 activity, reducing tumor growth and metastasis.CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation. 展开更多
关键词 Hepatocellular carcinoma Sorafenib Signal transducer and activator of transcription 3 extracellular signal regulated kinase Akt
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Correlation between receptor-interacting protein 140 expression and directed differentiation of human embryonic stem cells into neural stem cells 被引量:3
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作者 Zhu-ran Zhao Wei-dong Yu +7 位作者 Cheng Shi Rong Liang Xi Chen Xiao Feng Xue Zhang Qing Mu Huan Shen Jing-zhu Guo 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第1期118-124,共7页
Overexpression of receptor-interacting protein 140(RIP140) promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2(ERK1/2) signaling.However,involvement of RIP140 in human neural dif... Overexpression of receptor-interacting protein 140(RIP140) promotes neuronal differentiation of N2 a cells via extracellular regulated kinase 1/2(ERK1/2) signaling.However,involvement of RIP140 in human neural differentiation remains unclear.We found both RIP140 and ERK1/2 expression increased during neural differentiation of H1 human embryonic stem cells.Moreover,RIP140 negatively correlated with stem cell markers Oct4 and Sox2 during early stages of neural differentiation,and positively correlated with the neural stem cell marker Nestin during later stages.Thus,ERK1/2 signaling may provide the molecular mechanism by which RIP140 takes part in neural differentiation to eventually affect the number of neurons produced. 展开更多
关键词 nerve regeneration receptor-interacting protein 140 neural stem cells human embryonic stem cells directed differentiation Oct4 Sox2 Nestin extracellular regulated kinase 1/2 signaling pathway neural regeneration
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Activation of glycine site and GluN2B subunit of NMDA receptors is necessary for ERK/CREB signaling cascade in rostral anterior cingulate cortex in rats:Implications for affective pain 被引量:15
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作者 Hong Cao Wen-Hua Ren +2 位作者 Mu-Ye Zhu Zhi-Qi Zhao Yu-Qiu Zhang 《Neuroscience Bulletin》 SCIE CAS CSCD 2012年第1期77-87,共11页
Objective The rostral anterior cingulate cortex (rACC) is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors (NMDARs) are highly expressed in the rACC and mediate painrelated ... Objective The rostral anterior cingulate cortex (rACC) is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors (NMDARs) are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate (cAMP)/protein ki- nase A (PKA) and/or extracellular regulated kinase (ERK)/cAMP-response element-binding protein (CREB). The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC. Methods Immunohistochemistry and Western blot analy- sis were used to separately assess the expression of phospho-ERK (pERK) and phospho-CREB (pCREB) in vitro and in vivo. Double immunostaining was also used to determine the colocalization of pERK and pCREB. Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC, which was inhibited by the NMDAR antago- nist DL-2-amino-5-phospho-novaleric acid. Selective blockade of the NMDAR GluN2B subunit and the glycine- binding site, or degradation of endogenous D-serine, a co-agonist for the glycine site, significantly decreased the up- regulation of pERK and pCREB expression in the rACC. Further, the activated ERK predominantly colocalized with CREB. Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats, and these might be fundamental molecular mechanisms underlying pain affect. 展开更多
关键词 N-methyl-D-aspartate receptor glycine site GIuN2B D-SERINE extracellular regulated kinase/cAMP-response element-binding protein signaling pathway rostral anterior cingulate cortex
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The regulatory effect of ERK1/2 signal pathway on production of TNFα induced by LPS in mice Kupffer cells
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作者 张宇 蒋建新 +3 位作者 吉善和 单佑安 朱佩芳 周继红 《Chinese Journal of Traumatology》 CAS 2001年第3期139-142,共4页
Objective: To study the rule of ERK1/2 activity and regulative effect of ERK1/2 pathway on the production of pro inflammatory cytokine TNFα in mice Kupffer cells (mKC) induced by LPS, and to exploring novel methods t... Objective: To study the rule of ERK1/2 activity and regulative effect of ERK1/2 pathway on the production of pro inflammatory cytokine TNFα in mice Kupffer cells (mKC) induced by LPS, and to exploring novel methods to prevent and treat clinical patients of endotoxemia. Methods: Immunoprecipitate kinase assay and Western blotting analysis were used to detect the phosphorylated ERK1/2 kinase activity in mKC stimulated by LPS, and ELISA was used to study the effect of ERK1/2 signaling cascade on LPS induced TNFα production in mKC. Results: In mKC, LPS treatment resulted in transient and rapid increase of kinase activity of ERK1/2 that phosphorylated their specific substrate ELK 1, with maximal value at 30 minutes and a return near to baseline within 2 hours, and LPS induced ERK1/2 activity from LPS concentration of 10 pg/ml to the top activity at 100 ng/ml . No activity was observed in unstimulated mKC. Inhibition of the ERK1/2 pathway using the specific ERK 1/2 signal pathway inhibitor PD98059 caused a marked and concentration dependent reduction of TNFα production. Conclusions: The results show that LPS can markedly activate ERK1/2 pathway in mKC. PD98059 causes a significant and concentration dependent reduction of TNFα production. ERK1/2 may be a novel target to treat clinical patient of endotoxemia. 展开更多
关键词 Kupffer cells LIPOPOLYSACCHARIDES Tumor necrosis factor extracellular signal regulated kinase
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