Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2972-2983, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467687

RESUMO

There have been many clinical trials, systematic reviews/Meta-analysis proving that Xingnaojing Injection has a good clinical efficacy in treatment of cerebral ischaemic stroke, but with fewer comprehensive descriptions. In this study, an overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treating cerebral ischaemic stroke was performed to provide current situation of evidences and basis for clinical practice. CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science were retrieved through computers. A total of 6 literatures were included in this study. By AMSTAR-2 checklist and GRADE, the quality of included systematic reviews and the efficacy of Xingnaojing Injection were evaluated. The results of AMSTAR-2 checklist showed an extremely low quality for all of the 6 systematic reviews. According to the results of GRADE evaluation, among 55 outcomes, there were 2 outcomes with a medium quality, 4 outcomes with a low quality and 49 outcomes with an extremely low quality. The 6 systematic reviews reached a consistent conclusion that Xingnaojing Injection was effective in the treatment of cerebral ischaemic stroke. This therapy could improve the total efficacy, neurological deficit scores, hemodynamic and hemodynamic parameters. However, the methodolo-gical quality of all literatures was extremely low. The evidence levels of outcomes were between extremely low to medium. The effectiveness of Xingnaojing Injection in the treatment of cerebral ischaemic stroke still needs to be further verified by more high-quality studies. In the future, relevant clinical studies and systematic reviews/Meta-analysis shall be carried out in a strict accordance with relevant regulations.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Revisões Sistemáticas como Assunto
2.
Environ Microbiol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472190

RESUMO

Magnaporthe oryzae is an important plant pathogen that causes rice blast. Hse1 and Vps27 are components of ESCRT-0 involved in the multivesicular body (MVB) sorting pathway and biogenesis. To date, the biological functions of ESCRT-0 in M. oryzae have not been determined. In this study, we identified and characterized Hse1 and Vps27 in M. oryzae. Disruption of MoHse1 and MoVps27 caused pleiotropic defects in growth, conidiation, sexual development and pathogenicity, thereby resulting in loss of virulence in rice and barley leaves. Disruption of MoHse1 and MoVps27 triggered increased lipidation of MoAtg8 and degradation of GFP-MoAtg8, indicating that ESCRT-0 is involved in the regulation of autophagy. ESCRT-0 was determined to interact with coat protein complex II (COPII), a regulator functioning in homeostasis of the endoplasmic reticulum (ER homeostasis), and disruption of MoHse1 and MoVps27 also blocked activation of the unfolded protein response (UPR) and autophagy of the endoplasmic reticulum (ER-phagy). Overall, our results indicate that ESCRT-0 plays critical roles in regulating fungal development, virulence, autophagy and ER-phagy in M. oryzae.

3.
BMC Plant Biol ; 21(1): 281, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154532

RESUMO

BACKGROUND: As an important cash crop, the yield of peanut is influenced by soil acidification and pathogen infection. Receptor-like protein kinases play important roles in plant growth, development and stress responses. However, little is known about the number, location, structure, molecular phylogeny, and expression of RLKs in peanut, and no comprehensive analysis of RLKs in the Al stress response in peanuts have been reported. RESULTS: A total of 1311 AhRLKs were identified from the peanut genome. The AhLRR-RLKs and AhLecRLKs were further divided into 24 and 35 subfamilies, respectively. The AhRLKs were randomly distributed across all 20 chromosomes in the peanut. Among these AhRLKs, 9.53% and 61.78% originated from tandem duplications and segmental duplications, respectively. The ka/ks ratios of 96.97% (96/99) of tandem duplication gene pairs and 98.78% (646/654) of segmental duplication gene pairs were less than 1. Among the tested tandem duplication clusters, there were 28 gene conversion events. Moreover, all total of 90 Al-responsive AhRLKs were identified by mining transcriptome data, and they were divided into 7 groups. Most of the Al-responsive AhRLKs that clustered together had similar motifs and evolutionarily conserved structures. The gene expression patterns of these genes in different tissues were further analysed, and tissue-specifically expressed genes, including 14 root-specific Al-responsive AhRLKs were found. In addition, all 90 Al-responsive AhRLKs which were distributed unevenly in the subfamilies of AhRLKs, showed different expression patterns between the two peanut varieties (Al-sensitive and Al-tolerant) under Al stress. CONCLUSIONS: In this study, we analysed the RLK gene family in the peanut genome. Segmental duplication events were the main driving force for AhRLK evolution, and most AhRLKs subject to purifying selection. A total of 90 genes were identified as Al-responsive AhRLKs, and the classification, conserved motifs, structures, tissue expression patterns and predicted functions of Al-responsive AhRLKs were further analysed and discussed, revealing their putative roles. This study provides a better understanding of the structures and functions of AhRLKs and Al-responsive AhRLKs.


Assuntos
Alumínio/toxicidade , Arachis/efeitos dos fármacos , Arachis/enzimologia , Evolução Molecular , Proteínas Serina-Treonina Quinases/genética , Receptores de Superfície Celular/genética , Sequência de Aminoácidos , Arachis/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Genes de Plantas , Família Multigênica , Filogenia , Proteínas Serina-Treonina Quinases/fisiologia , Receptores de Superfície Celular/fisiologia
4.
Oncogene ; 39(43): 6704-6718, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32958832

RESUMO

Autophagy can protect stressed cancer cell by degradation of damaged proteins and organelles. However, the regulatory mechanisms behind this cellular process remain incompletely understood. Here, we demonstrate that RSK2 (p90 ribosomal S6 kinase 2) plays a critical role in ER stress-induced autophagy in breast cancer cells. We demonstrated that the promotive effect of RSK2 on autophagy resulted from directly binding of AMPKα2 in nucleus and phosphorylating it at Thr172 residue. IRE1α, an ER membrane-associated protein mediating unfolded protein response (UPR), is required for transducing the signal for activation of ERK1/2-RSK2 under ER stress. Suppression of autophagy by knockdown of RSK2 enhanced the sensitivity of breast cancer cells to ER stress both in vitro and in vivo. Furthermore, we demonstrated that inhibition of RSK2-mediated autophagy rendered breast cancer cells more sensitive to paclitaxel, a chemotherapeutic agent that induces ER stress-mediated cell death. This study identifies RSK2 as a novel controller of autophagy in tumor cells and suggests that targeting RSK2 can be exploited as an approach to reinforce the efficacy of ER stress-inducing agents against cancer.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Autofagia , Neoplasias da Mama/patologia , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Núcleo Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células MCF-7 , Camundongos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Arthritis Rheumatol ; 68(8): 2003-15, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26945694

RESUMO

OBJECTIVE: Understanding the pathogenesis of systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models of SSc that recapitulate distinct subsets of disease at the molecular level have not been delineated. We applied interspecies comparative analysis of genomic data from multiple mouse models of SSc and patients with SSc to determine which animal models best reflect the SSc intrinsic molecular subsets. METHODS: Gene expression measured in skin from mice with sclerodermatous graft-versus-host disease (GVHD), bleomycin-induced fibrosis, Tsk1/+ or Tsk2/+ mice was mapped to human orthologs and compared to SSc skin biopsy-derived gene expression. Transforming growth factor ß (TGFß) activation was assessed using a responsive signature in mice, and tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression was measured in SSc patient and mouse skin. RESULTS: Gene expression in skin from mice with sclerodermatous GVHD and bleomycin-induced fibrosis corresponded to that in SSc patients in the inflammatory molecular subset. In contrast, Tsk2/+ mice showed gene expression corresponding to the fibroproliferative SSc subset. Enrichment of a TGFß-responsive signature was observed in both Tsk2/+ mice and mice with bleomycin-induced skin fibrosis. Expression of TNFRSF12A (the TWEAK receptor/fibroblast growth factor-inducible 14) was elevated in skin from patients with fibroproliferative SSc and the skin of Tsk2/+ mice. CONCLUSION: This study reveals similarities in cutaneous gene expression between distinct mouse models of SSc and specific molecular subsets of the disease. Different pathways underlie the intrinsic subsets including TGFß, interleukin-13 (IL-13), and IL-4. We identify a novel target, Tnfrsf12a, with elevated expression in skin from patients with fibroproliferative SSc and Tsk2/+ mice. These findings will inform mechanistic and translational preclinical studies in SSc.


Assuntos
Modelos Animais de Doenças , Escleroderma Sistêmico/genética , Animais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos
6.
CNS Neurosci Ther ; 19(1): 48-52, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23167919

RESUMO

BACKGROUND AND PURPOSE: Few reports concerned on recombinant tissue plasminogen activator (rt-PA) treatment in stroke patients with decreased consciousness. This study assesses the efficacy and safety of intravenous rt-PA administration within 4.5 h in stroke patients with decreased consciousness. METHODS: A total of 136 stroke patients with decreased consciousness, who received or not rt-PA intravenously within 4.5 h after stroke onset from Jiangsu province of China from 2009 to 2012, were reviewed retrospectively. Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), intracranial hemorrhage rate, and mortality were used to determine patient outcome when discharged. A 3-month outcome was calculated by modified Rankin Scale (mRS) with score 0 to 1 considered favorable outcome. RESULTS: Baseline characteristics of two groups were similar. When discharged, no significant differences were observed regarding NIHSS score (P = 0.994) or GCS score (P = 0.591) between groups. After 3 months, 22.8% patients in rt-PA group had favorable outcome as compared with 7.5% patients in control group (P = 0.014). Treatment with rt-PA did not significantly increase incidence of hemorrhage (P = 0.494) or mortality (P = 0.169). CONCLUSIONS: Intravenous rt-PA administration within 4.5 h after onset of symptoms benefited stroke patients with abnormal consciousness.


Assuntos
Estado de Consciência/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Tempo
7.
OMICS ; 15(10): 673-82, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21978395

RESUMO

Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.


Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Mensageiro/metabolismo , Adulto , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Simulação por Computador , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Redes e Vias Metabólicas/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Modelos Genéticos , Gradação de Tumores , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/genética
8.
OMICS ; 15(1-2): 49-60, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20726781

RESUMO

Transcription factors (TFs) are crucial modulators of gene regulation during the development and progression of tumors. We previously reported the activation of TFs in nasopharyngeal carcinoma (NPC) cell lines. In this study, we explored the activity profiles of TFs in Protein/DNA array data of a 12-tissue independent set and a 13-tissue pooled set of NPC that included different clinical stages. TFs associated with tumor progression were revealed using a generalized linear model-based regression analysis. Immunohistochemical analysis of clinical NPC samples was used to validate the results of array analysis. We identified 26 TFs that showed increased activities. Of these 26 TFs, 16 were correlated with clinical stages. Activity changes of AP2 and ATF/CREB were confirmed by electrophoretic mobility shift assay (EMSA), and increased expression of AP2α, ß, γ, ATF2, and ATF1 in nuclei of tumor cells was associated with clinical stages. In addition, the expressions of AP2α, ATF2, and ATF1 were correlated with those of their target genes (epithelia growth factor receptor (EGFR) and matrix metalloproteinase 2 (MMP-2), respectively). This study provides data and valuable clues that can be used to further investigate the laws of gene transcription regulation in NPC and to identify suitable targets for the development of TF-targeted antitumor agents.


Assuntos
Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Transcrição/metabolismo , Sequência de Bases , Western Blotting , Sondas de DNA , Progressão da Doença , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
Clin Chim Acta ; 412(1-2): 112-9, 2011 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-20869360

RESUMO

BACKGROUND: Serum peptidome profile is a promising tool to identify physiologic or pathologic conditions. Stable serum peptidome profiles with high quality are essential for serum peptidome research. The aim of this study is to examine the impact of experimental and demographic variables in serum peptide profiling. METHODS: Magnetic bead combined with MALDI-TOF mass spectrometry was performed to evaluate the efficacy of various variables including the treatment of blood, the pretreatment of serum (magnetic beads and ultrafiltrate centrifugal filters), the mass spectrometry and the data handling. The influence of age and gender on serum peptidome was also analyzed in 123 healthy volunteers. RESULTS: The results showed that the sampling processing procedures were crucial for the serum peptidome profiles. There were obvious differences on the serum peptidome profiles between the age groups younger and older than 30. There was no difference between gender groups. CONCLUSIONS: A number of optimized and standardized variables should be defined in serum peptidome research based on magnetic beads and MALDI-TOF mass spectrometry. An extremely strict standard procedure and considerate arrangement should be applied.


Assuntos
Análise Química do Sangue/métodos , Demografia , Magnetismo , Peptídeos/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto , Fatores Etários , Análise Química do Sangue/normas , Fracionamento Químico , Cristalização , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/isolamento & purificação , Padrões de Referência , Fatores Sexuais , Manejo de Espécimes/normas , Fatores de Tempo
10.
Mol Cell Biochem ; 345(1-2): 283-90, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20859756

RESUMO

Nasopharyngeal carcinoma-associated gene 6 (NGX6) was shown to be a novel putative tumor suppressor gene in colon cancer. The purpose of this study is to investigate its role in regulation of miRNA expression for in the hopes of translating this data into a novel strategy in control of colon cancer. In this study colon cancer HT-29 cells were stably transfected with NGX6 or vector-only plasmid and then subjected to miRNA array analysis, and Q-RT-PCR was then used to verify miRNA array data. Then bioinformatic analyses using Sanger, Target Scan, and MicroRNA software were performed to obtain data on the target genes of each miRNA and define their function. Our results showed that 14 miRNAs were found to be differentially expressed in NGX6-transfected cells compared to the control cells. In particular, miR-126, miR-142-3p, miR-155, miR-552, and miR-630 were all upregulated, whereas miR-146a, miR-152, miR-205, miR-365, miR-449, miR-518c, miR-584, miR-615, and miR-622 were downregulated after NGX6 transfection. Q-RT-PCR confirmed all of these miRNAs, and invalidated miR-552 and miR-630. Furthermore, bioinformatic analyses of these 12 miRNAs, among these miRNAs, target genes of miR-615 are unclear, another 11 miRNAs produced a total of 254 potential target genes and further study showed that these genes together formed a regulatory network that contributes to apoptosis, mobility/migration, hydrolysis activity, and molecular signaling through targeting JNK and Notch pathways. Taken together, these results have suggested that NGX6 plays an important role in regulation of apoptosis, mobility/migration, and hydrolase as well as activity of JNK and Notch pathways through NGX6-mediated miRNA expression. Further investigation will reveal the function of these differentially expressed miRNAs and verify expression of the miRNA-targeted genes for development of novel strategies for better control of colon cancer.


Assuntos
Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana , MicroRNAs/genética , Proteínas Supressoras de Tumor , Redes Reguladoras de Genes , Células HT29 , Humanos , MAP Quinase Quinase 4/metabolismo , Receptores Notch/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética
11.
Lab Invest ; 90(2): 196-209, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19997065

RESUMO

Epstein-Barr virus (EBV) is closely associated with several malignancies, including nasopharyngeal carcinoma. To investigate the EBV activity in tumor development, we tried to establish a malignant model of EBV-infected cells in nude mice. On the basis of the Maxi-EBV system, a human embryonic kidney epithelial cell line (293) with a low malignant potential was used for a stable EBV genome infection. The derived cell line, termed 293-EBV, exhibited obvious morphological transformation and significantly increased growth ability, with the cell cycle redistributed. The clonability and tumorigenicity were also substantially accelerated. In 293-EBV cells, the expression level of the transcription factor NF-kappaB and JNK2 were upregulated. The result suggested that latent membrane protein 1 (LMP1) was an important viral protein responsible for the enhanced malignant potential. Matured and budding virus particles were observed in tumor tissues, confirming the spontaneous reactivation of EBV from latent genome to lytic cycle at the site of tumor development. Primary culture of tumor tissues showed two patterns about the EBV maintenance or not in newly grown cells, and this was dependent on the thickness of the planted tissues. Moreover, the tumor cells lost EBV genome easily when subcultured at low density. Our findings revealed the cell-to-cell contact mechanism, which was required for the EBV maintenance in the tumor cells during the expansion of EBV-infected cells. This mechanism might give an explanation to the phenomenon that EBV genome in epithelial tumor cells becomes easily lost during subculture in vitro. Our results provided further evidence of a function for EBV in the etiology of tumor development.


Assuntos
Carcinoma/virologia , Linhagem Celular Transformada , Herpesvirus Humano 4/fisiologia , Latência Viral/fisiologia , Animais , Humanos , Camundongos , Camundongos Nus , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transplante de Neoplasias , Regulação para Cima
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 33(10): 892-7, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-19001730

RESUMO

OBJECTIVE: To explore the effect of all-trans-retinoic acid (ATRA) on the growth inhibition and cellular differentiation of C6 glioma cells. METHODS: Human glioma C6 cells were treated with 5 mg/L ATRA,and the inhibition of cell growth was assessed by methyl thiazolyl tetrazolium assay. The differentiation of C6 cells was determined by flow cytometry, microscopy,transmission electron microscope, and immunohistochemical technique. RESULTS: Treatment of ATRA could result in the growth inhibition of C6 cells, and the cell density significantly decreased(P<0.01). The cell cycle distribution was changed, G0/G1 phase was prolonged, and cells at S phase decreased(P<0.01). The C6 glioma cells displayed normal fibroblast-like morphology under the microscope before the induction, and the ATRA-treated C6 cells became slightly long, turned into round in the middle, and had protrusions at both ends. The ATRA-treated C6 cells did not display obvious apoptosis by flow cytometry(P>0.05).Whereas, early apoptosis was observed under the transmission electron microscope, the vacuoles increased, the mitochondria and endoplasmic reticulum were abundant in the cytoplasm, and the cellular structures tended to be normal.The expression of glial fibrillaryacidic protein in C6 cells increased in the treatment group. CONCLUSION: ATRA can inhibit the proliferation, and induce the differentiation of C6 glioma cells.


Assuntos
Neoplasias Encefálicas/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Glioma/patologia , Tretinoína/farmacologia , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Células Tumorais Cultivadas
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 33(7): 553-8, 2008 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-18667764

RESUMO

There is obvious allele disequilibrium in nasopharyngeal carcinoma at chromosome 3p, 9p, 6q, 11q, 13q and 14q. Nasopharyngeal carcinoma (NPC) susceptibility/suppressor gene candidates were obtained by molecular biology methods,such as cDNA representational difference ana-lysis. The functional research of NPC susceptibility/ suppressor gene candidates indicated: (1) The increased expression of Cx contributed to obstacles of gap junctional intercellular communication (GJIC), and resulted an aberration of GJIC; (2) BRD7, a transcript factor, was associated with cell cycle regulation; (3) NAG7,an estrogen receptor repressor, inhibited the invasive potential of human NPC cells by regulating ERalpha expression and the H-ras/p-c-Raf and JNK/AP-1/MMP1 signaling pathways; (4) NGX6, a metastasis-associated protein, can negative-regulate EGF/Ras/MAPK signaling transduction pathway, and interact with ezrin protein to inhibit invasion and metastasis of NPC cells; (5) SPLUNC1, a secreted protein, can inhibit the bacterium clone formation, and is an innate immune molecule. These data will lay an important foundation for the NPC mechanism.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Genômica/métodos , Glicoproteínas/genética , Proteínas de Membrana/genética , Neoplasias Nasofaríngeas/genética , Fosfoproteínas/genética , Proteínas Supressoras de Tumor/genética , Biomarcadores Tumorais , Humanos , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , RNA Longo não Codificante , RNA não Traduzido , Células Tumorais Cultivadas
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(5): 735-41, 2007 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18007062

RESUMO

OBJECTIVE: To explore the effect of LRRC4 on the mobility and invasion of glioblastomas U251 cells through the SDF-1alpha/CXCR4 axis. METHODS: RT-PCR, transfilter cell invasion assay, adhesion assay, scraping test, scrape loading, and dye transfer assay were used to determine the effect of LRRC4 on U251 cells. RESULTS: SDF-1 alpha could increase the invasion in U251 which expressed CXCR4. The reintroduction of LRRC4 in U251 cells could inhibit the expression of CXCR4. LRRC4 also inhibited the adhesion ability of U251 to ECV304 as well as the mobility and invasion ability in vitro, which was mediated by the SDF-1alpha/CXCR4 axis. Furthermore, LRRC4 could greatly enhance the gap junctional intercellular communication of U251 cells. CONCLUSION: The reintroduction of LRRC4 in U251 cells can inhibit the expression of CXCR4 and the SDF-1alpha/CXCR4 axis-mediated cell invasion in vitro.


Assuntos
Quimiocina CXCL12/metabolismo , Glioblastoma/patologia , Proteínas do Tecido Nervoso/genética , Receptores CXCR4/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Humanos , Invasividade Neoplásica
15.
J Cell Sci ; 120(Pt 23): 4230-40, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18032789

RESUMO

The signals mediating transforming growth factor beta (TGFbeta)-stimulated kidney fibrogenesis are poorly understood. We previously reported TGFbeta-stimulated, Smad-mediated collagen production by human kidney mesangial cells, and that ERK MAP kinase activity optimizes collagen expression and enhances phosphorylation of the Smad3 linker region. Furthermore, we showed that disrupting cytoskeletal integrity decreases type I collagen production. Focal adhesion kinase (FAK, PTK2) activity could integrate these findings. Adhesion-dependent FAK Y397 phosphorylation was detected basally, whereas FAK Y925 phosphorylation was TGFbeta1-dependent. By immunocytochemistry, TGFbeta1 stimulated the merging of phosphorylated FAK with the ends of thickening stress fibers. Cells cultured on poly-L-lysine (pLL) to promote integrin-independent attachment spread less than those on control substrate and failed to demonstrate focal adhesion (FA) engagement with F-actin. FAK Y397 phosphorylation and ERK activity were also decreased under these conditions. In cells with decreased FAK Y397 phosphorylation from either plating on pLL or overexpressing a FAK Y397F point mutant, serine phosphorylation of the Smad linker region, but not of the C-terminus, was reduced. Y397F and Y925F FAK point mutants inhibited TGFbeta-induced Elk-Gal activity, but only the Y397F mutant inhibited TGFbeta-stimulated collagen-promoter activity. The inhibition by the Y397F mutant or by culture on pLL was prevented by co-transfection of constitutively active ERK MAP kinase kinase (MEK), suggesting that FAK Y397 phosphorylation promotes collagen expression via ERK MAP kinase activity. Finally, Y397 FAK phosphorylation, and both C-terminal and linker-region Smad3 phosphorylation were detected in murine TGFbeta-dependent kidney fibrosis. Together, these data demonstrate adhesion-dependent FAK phosphorylation promoting TGFbeta-induced responses to regulate collagen production.


Assuntos
Colágeno Tipo I/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Células Mesangiais/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Tirosina/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Técnica Indireta de Fluorescência para Anticorpo , Quinase 1 de Adesão Focal/química , Quinase 1 de Adesão Focal/genética , Genes Reporter , Humanos , Imuno-Histoquímica , Luciferases/metabolismo , Fosforilação , Plasmídeos , Proteínas Recombinantes/metabolismo , Transfecção , Fator de Crescimento Transformador beta1/genética
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(3): 373-9, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17611308

RESUMO

OBJECTIVE: To prepare anti-LRRC4 polyclonal antibody and analyze the correlation between the expression of LRRC4 and pathological grades of gliomas in rabbits. METHODS: Appropriate protein sequence with good hydrophilicity and antigenicity was chosen by analyzing with DS Gene 1.1 software. The corresponding nucleic acid sequence amplified by PCR was used to construct a recombinant pGEX-4T-2/276 bp. E.coli JM109 transformed with the recombinant was induced by IPTG to express GST-fusion protein, and the fusion protein expressed as insoluble inclusion bodies. Then the purified inclusion body was used to immunize rabbits. Once the titer of antiserum reached 1:10(8) by indirect ELISA, the serum was collected and purified. The expression-profile of LRRC4 in embryonic tissues and gliomas with various pathological grades were obtained by western blot and immunohistochemistry with the anti-LRRC4 polyclonal antibody. RESULTS: The highly specific anti-LRRC4 polyclonal antibody whose titer reached 1:10(8) was prepared. The relatively specific expression of LRRC4 was detected in the normal brain, but reduced expression or loss of expression in gliomas was also noticed by immunohistochemistry, and there was a correlation between the expression level of lrrc4 and the pathological grade of gliomas. CONCLUSION: The anti-LRRC4 polyclonal antibody with high titer and specificity has been obtained. A correlation between the expression level of LRRC4 and the pathological grade of gliomas is detected, which lays the foundation for advanced research of LRRC4.


Assuntos
Anticorpos Monoclonais/imunologia , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Animais , Especificidade de Anticorpos/imunologia , Western Blotting , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioma/imunologia , Glioma/patologia , Imuno-Histoquímica , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/imunologia , Coelhos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/imunologia
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(2): 213-20, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17478925

RESUMO

Omics docking study for polygenic inheritance tumors has become an important strategy in oncology research. This review focuses on the conceptions and technologies of omics, and puts forward the central contents and omics docking for polygenic inheritance tumor to reveal the role of molecular changes at different stages of polygenic inheritance tumor at multidisciplinary and multilayer level. It is a new strategy to explore the mechanism of tumor carcinogenesis, and to regulate the network, key molecules, and drug target by combined biology effects.


Assuntos
Genômica/métodos , Herança Multifatorial/genética , Neoplasias/genética , Neoplasias/metabolismo , Proteômica/métodos , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Glicoproteínas/biossíntese , Glicoproteínas/genética , Humanos , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Fosfoproteínas/biossíntese , Fosfoproteínas/genética , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(2): 221-5, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17478926

RESUMO

Metabolomics is a new science and technology, which it refers to a holistic analytical approach to all the low molecular weight metabolites in an organism or a cell. In this paper, the definition and objective of metabolomics are provided, and the current application of metabolomic research in malignant tumors (diagnosis and therapy) are summarized.


Assuntos
Metabolismo , Neoplasias/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Genômica/métodos , Genômica/tendências , Humanos , Modelos Biológicos , Neoplasias/genética , Proteômica/métodos , Proteômica/tendências , Transcrição Genética
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(2): 226-30, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17478927

RESUMO

OBJECTIVE: To explore the effect of LRRC4, a glioma suppressive gene, on blocking U251 cells in G0/G1 by MAPK signaling pathway. METHODS: LRRC4 was transfected into U251 cells, and at 24 hour of post-transfection, cells were split at a 1:3 dilution, challenged with 500 microg /mL G418 and formed a stable transfected clone pool. RT-PCR, Northern blot and Western blot were used to identify the stable transfectants. ERK, JNK and P38 expression changes were analyzed by Western blot. FACS analysis, Luciferase reporter gene assay and Western blot were used to detect the cell cycle and cyclin D1. RESULTS: LRRC4 down-regulated the expression of phosphorylated ERK2 and up-regulated the expression of total protein JNK2 (a key molecule of MAPK signaling pathway) and phosphorylated c-Jun. LRRC4 decreased the expression of mutation P53, cyclin D1 activation and its expression. U251 cells were blocked in G0/G1 by LRRC4. CONCLUSION: LRRC4 can decrease JNK2, up-regulate the phosphoralated c-Jun, down-regulate mutant P53 and cyclin D1, and therefore block U251 cells in G0/G1.


Assuntos
Fase G1/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Fase de Repouso do Ciclo Celular/fisiologia , Northern Blotting , Western Blotting , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Citometria de Fluxo , Fase G1/genética , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Luciferases/genética , Luciferases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fase de Repouso do Ciclo Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 32(2): 231-4, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17478928

RESUMO

OBJECTIVE: To examine the expression absence of LRRC4 gene in glioblastoma cell lines. METHODS: RT-PCR and Northern blot were used to detect the expression of LRRC4 gene in 6 glioblastomas cells lines. Polymerase chain reaction and DNA sequencing were used to screen the LRRC4 gene mutation, while bioinformation assay was used to search for the reason of LRRC4 gene absence in U251 cell lines. RESULTS: The expression of LRRC4 was absent in 6 malignant glioma cell lines (U251, U87, BT325, SF126, SF767 and M17), which were examined by Northern-blot and RT-PCR assay. All sequencing of PCR products from gDNA of SF126, SF767, and M17 cell lines contained the point mutation at the same position ( LRRC4 geneT977A) (3/5), which was a synonymous mutation. However, PCR products from gDNA of U251 and U87 cell lines (2/5) were not obtained. The expression absence of LRRC4 was ascribed to the loss of homozygosity of 7q32-ter in U251 cell lines. CONCLUSION: The expression of LRRC4 gene is absent in glioblastoma cell lines, and it offers the important experiment proof for LRRC4 to act as a new candidate of brain tumor suppressor gene from glioma. The loss of homozygosity of 7q32-ter contributed to the expression absence of LRRC4 in U251 cell lines.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Mutação Puntual , Sequência de Bases , Northern Blotting , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Análise Mutacional de DNA , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...