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1.
Emerg Microbes Infect ; 8(1): 734-748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130074

RESUMO

Many pathogens infect hosts through various immune evasion strategies. However, the molecular mechanisms by which pathogen proteins modulate and evade the host immune response remain unclear. Enterohemorrhagic Escherichia coli (EHEC) is a pathological strain that can induce mitogen-activated protein (MAP) kinase (Erk, Jnk and p38 MAPK) and NF-κB pathway activation and proinflammatory cytokine production, which then causes diarrheal diseases such as hemorrhagic colitis and hemolytic uremic syndrome. Transforming growth factor ß-activated kinase-1 (TAK1) is a key regulator involved in distinct innate immune signalling pathways. Here we report that EHEC translocated intimin receptor (Tir) protein inhibits the expression of EHEC-induced proinflammatory cytokines by interacting with the host tyrosine phosphatase SHP-1, which is dependent on the phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction. Taken together, these results suggest that EHEC Tir negatively regulates proinflammatory responses by inhibiting the activation of TAK1, which is essential for immune evasion and could be a potential target for the treatment of bacterial infection.


Assuntos
Escherichia coli Êntero-Hemorrágica/patogenicidade , Infecções por Escherichia coli/fisiopatologia , Proteínas de Escherichia coli/metabolismo , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , MAP Quinase Quinase Quinases/antagonistas & inibidores , Receptores de Superfície Celular/metabolismo , Fatores de Virulência/metabolismo , Animais , Infecções por Escherichia coli/microbiologia , Células HEK293 , Humanos , Macrófagos Peritoneais , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Células RAW 264.7
2.
Adv Exp Med Biol ; 1024: 37-61, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28921464

RESUMO

Inflammation is usually the defensive reaction of the immune system to the invasion of pathogen and the exogenous objects. The activation of inflammation helps our body to eliminate pathogenic microbe, virus, and parasite harming our health, while under many circumstances inflammation is the direct cause of the pathological damage in tissues and dysfunction of organs. The posttranslational modification (PTM) of the inflammatory pathways, such as TLR pathways, RLR pathways, NLR pathway, intracellular DNA sensors, intracellular RNA sensors, and inflammasomes, is crucial in the regulation of these signaling trails. Ubiquitination, phosphorylation, polyubiquitination, methylation, and acetylation are the main forms of the PTM, and they respectively play different roles in signaling regulation. The effects of the PTM range from the production of pro-inflammatory factors and the interaction between adaptors and receptors to cell translocation in response to the infectious or other dangerous factors. In this chapter, we will have an overview of the different ways of the posttranslational modifications in different inflammatory signaling pathways and their essential roles in regulation of inflammation.


Assuntos
Regulação da Expressão Gênica/imunologia , Inflamação/metabolismo , Processamento de Proteína Pós-Traducional/imunologia , Transdução de Sinais/imunologia , Animais , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Inflamassomos , Inflamação/imunologia , Proteínas NLR/genética , Proteínas NLR/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Fosforilação , RNA/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores Toll-Like/imunologia , Ubiquitinação
3.
Cell Mol Immunol ; 14(3): 237-244, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27796284

RESUMO

To successfully infect host cells and evade the host immune response, a type III secretion system (T3SS) is commonly used by enteric bacterial pathogens such as enteropathogenic Escherichia coli (EPEC). Recent findings have revealed that various effectors are injected into host cells through the T3SS and exert an inhibitory effect on inflammatory signaling pathways, subverting the immune responses to these pathogens. Here we review recent studies aimed at addressing the modulation of several important inflammatory signaling pathways modulated by EPEC effector proteins, such as the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, which provides insight into the unfinished work in this unexplored field and helps to identify novel positions in inflammatory signaling networks for EPEC effectors.Cellular & Molecular Immunology advance online publication, 31 October 2016; doi:10.1038/cmi.2016.52.


Assuntos
Escherichia coli Enteropatogênica/patogenicidade , Proteínas de Escherichia coli/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Inflamação/microbiologia , Transdução de Sinais , Fatores de Virulência/metabolismo , Animais , Humanos , Inflamação/patologia
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(8): 677-82, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26733024

RESUMO

OBJECTIVE: To understand the distribution of esophageal squamous cell cancer and precursor lesions in high-risk areas of China, and to provide evidence for determining the reference ranges of detection rates in high-risk areas. METHODS: Endoscopy with Lugol's iodine staining was performed on 15 709 local residents aged 40 to 69 years old in Linzhou of Henan province and Feicheng of Shandong province from 2005-2009. 35 cases without accurate pathology diagnosis and 11 cases with vital disease before screening were excluded. 15 663 subjects were enrolled in this study. Compliance was calculated by the percentage of the people who had endoscopic screening among the target population. Chi-square test and trend chi-square test were used to compare the distribution differences in age, gender and areas of esophageal squamous cell cancer and precancer. 95% CI of the detection rates was then employed to represent the reference ranges of esophageal squamous cell cancer and precursor lesions. RESULTS: The compliance rate of screening endoscopy of this study was 49.36% (15 709/31 826) of all, and female's compliance (54.05%, 8 447/15 628) was much higher than that of male (44.83%, 7 262/16 198) (χ(2) = 88.14, P < 0.001). The detection rates of basal cell hyperplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia and esophageal squamous cell cancer of males were 4.17% (302/7 246), 17.22% (1 248/7 246), 1.67% (121/7 246), 0.83% (60/7 246), and were higher than that of females (3.45% (290/8 417), 14.82% (1 247/8 417), 1.41% (119/8 417), 0.48% (40/8 417), respectively). Except for high-grade intraepithelial neoplasia, the detection rates of male were higher than that of female (P values were 0.018, < 0.001, 0.960, 0.006). The detection rates of all grades of precursor lesions increased with age rising (all P values < 0.001), among which the detection rates of the mentioned four lesions for 40-44 years old were 2.69% (94/3 500), 8.11% (284/3 500), 0.40% (14/3 500), 0.14% (5/3 500), and that of 65-69 years old were 5.46% (46/843), 23.25% (196/843), 3.68% (31/843), 2.14% (18/843). The proportion of esophageal precursor lesion of Linzhou were higher than that of Feicheng observably except for esophageal squamous cell cancer (P values were < 0.001, < 0.001, < 0.001, 0.437). The detection rates of the four lesions of Linzhou and Feicheng were 4.90% (504/10 287), 17.37% (1 787/10 287), 1.79% (184/1 0287), 0.60% (62/10 287) and 1.64% (88/5 376), 13.17% (708/5 376), 1.04% (56/5 376), 0.71% (38/5 376). The 95% CI of detection rates of various lesions were, 3.78% (3.48%-4.08%) for basal cell hyperplasia, 15.93% (15.37%-16.50%) for low-grade intraepithelial neoplasia, 12.31% (11.79%-12.82%) for mild dysplasia and 3.62% (3.33%-3.91%) for moderate hyperplasia, 1.53% (1.34%-1.72%) for high-grade intraepithelial neoplasia and 0.64% (0.51%-0.76%) for esophageal squamous cell cancer, respectively. CONCLUSION: Up to 21.88% residents that were asymptomatic were suffered from esophageal squamous cancer or precursor lesions in high-risk areas in China. The distribution of esophageal squamous cell cancer and precursor lesions was closely related to the gender and the age, which suggested that males were supposed to be paid more attention to.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Endoscopia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Iodetos , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo
5.
Genomics Proteomics Bioinformatics ; 9(1-2): 30-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21641560

RESUMO

To enrich the genomic information of the commercially important fish species, we obtained 5,063 high-quality expressed sequence tags (ESTs) from the muscle cDNA database of the mandarin fish (Siniperca chuatsi). Clustering analysis yielded 1,625 unique sequences including 443 contigs (from 3,881 EST sequences) and 1,182 singletons. BLASTX searches showed that 959 unique sequences shared homology to proteins in the NCBI non-redundant database. A total of 740 unique sequences were functionally annotated using Gene Ontology. The 1,625 unique sequences were assigned to Kyoto Encyclopedia of Genes and Genomes reference pathways, and the results indicated that transcripts participating in nucleotide metabolism and amino acid metabolism are relatively abundant in S. chuatsi. Meanwhile, we identified 15 genes to be abundantly expressed in muscle of the mandarin fish. These genes are involved in muscle structural formation and regulation of muscle differentiation and development. The most remarkable gene in S. chuatsi is nuclease diphosphate kinase B, which is represented by 449 EST sequences accounting for 8.86% of the total EST sequences. Our work provides a transcript profile expressed in the white muscle of the mandarin fish, laying down a foundation in better understanding of fish genomics.


Assuntos
Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica , Músculo Esquelético/metabolismo , Perciformes/genética , Animais , Metaboloma , Anotação de Sequência Molecular , Núcleosídeo-Difosfato Quinase/genética , Perciformes/metabolismo
6.
Dongwuxue Yanjiu ; 31(2): 141-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20545003

RESUMO

At present, transcription analysis of gene expression commonly uses housekeeping genes as control for normalization. In this study, the expression levels of three housekeeping genes including GAPDH, beta-actin, and 18S rRNA in six tissues and five developmental stages of the Mandarin fish Siniperca chuatsi were assayed with quantitative real-time PCR (qPCR). Differences in expression levels were analyzed using geNorm program. The results demonstrate that beta-actin is the most stable gene at developmental stages and GAPDH is the most stable in different tissues. While 18S rRNA expression during development is differentially regulated, which indicates it is suitable as an internal control for gene expression normalization at the developmental level. Overall, the data suggest that the two most stable housekeeping genes are enough to accurately calibrate gene expression in S. chuatsi. The significance of this study provided convincing references and methodology for housekeeping gene selection and normalization in gene expression analysis with regular PCR or qPCR.


Assuntos
Perfilação da Expressão Gênica , Expressão Gênica , Actinas , Animais , Perciformes/genética , Reação em Cadeia da Polimerase em Tempo Real , Padrões de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 42(5): 345-8, 2008 May.
Artigo em Chinês | MEDLINE | ID: mdl-18844086

RESUMO

OBJECTIVE: To observe the distribution of the pre-cancerous condition and pathological changes of esophageal cancer of the community residents in high-incidence area, and to provide etiological evidences for secondary prevention. METHODS: An iodine-staining endoscope census was conducted in 9536 residents with high-risk factors at Feicheng, a high esophageal cancer incidence community in Shandong province. Of which, 1507 pathologic biopsies were performed and chi2 test administrated. RESULTS: There was no statistical significance found in biopsy pathologic diagnosis between females and males among 1507 samples. The mild and medium atypical hyperplasia was taken as pre-cancerous condition and severe atypical hyperplasia was taken as pre-cancerous lesion. Taking all the population attending census as denominator, the detection rate of the precancerous state and precancerous lesion were 6.98% (294/4214) and 1.23% (52/4214) for the males, and 3.68% (196/5322) and 0.47% (25/5322) for the females, respectively. A statistical significance was observed when comparing males with females (chi2 were 52.349 and 15.267, respectively, P < 0.05). Analyzed by age group, severe atypical hyperplasia pathological changes were mainly distributed in the age group of 50- and 65-. The constituent ratio between 45 - and 50 - was the highest for CIS. Early carcinoma was mainly distributed in five age groups from 45- to 65-. It showed that high incidence town had a high detection rate of cancer and pathological changes of esophageal cancer in the analysis of urban and rural distribution. CONCLUSION: The distribution of the pre-cancerous state and pathological changes of esophageal cancer of the residents should have provided a scientific basis for the primary and secondary prevention.


Assuntos
Neoplasias Esofágicas/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Serviços de Saúde Comunitária , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle , Serviços Preventivos de Saúde
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 41 Suppl: 56-61, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17767859

RESUMO

OBJECTIVE: To investigate the risk factors related to the esophageal squamous cell cancer in Feicheng county in Shandong province. METHODS: A case-control study was carried out in Feicheng county. There were two parts consisted in the cases. 253 cases, aged from 40 to 69 years old, were recruited from the screened endoscopic survey program from January 2004 to December 2006. The other part of cases was recruited from the people's Hospital of Feicheng city. 8159 subjects whose had normal endoscope test result were recruited as the control group. Besides cardiograph and ventral ultrasound examination the screening program also included an endoscope test during which mucosal stain with 1.2% iodine solution. The biopsies were taken from the screen and underwent pathologic evaluation by two pathologists; A self-administrative questionnaire survey was conducted in all the subjects to collect information about smoking, alcohol consumption and dietary. The binary Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (95% CI). The study protocol was approved by the local ethics committee and the study was conducted with the informed consents of all the study subjects. RESULTS: There were 235 esophageal cancers cases (70 identified in screening program, 183 were hospitalized patients) and 8159 controls in the case-control study. Three potential confounders were detected after univariate analysis. After adjusted the three confounders, age, sex and education, we found, smoking, alcohol drinking were the top ranked risk factors for esophageal cancer. When combing smoking and alcohol drinking, the or was 2.73 (95% CI: 1.54 - 4.82) for male, and the proportional attribute relative risk was 51.47%. We also observed that more dietary cellulose and vitamin C intake have protective effects. CONCLUSION: Smoking and alcohol drinking could increase the risk of esophageal cancer, and taking more dietary cellulose and vitamin C might decrease the risk.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Adulto , Idoso , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
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