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1.
Int J Syst Evol Microbiol ; 70(10): 5473-5478, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32886590

RESUMO

A Gram-stain-negative, non-motile, coccus-shaped, catalase- and oxidase-positive, facultatively anaerobic and pink-pigmented bacterium, designated strain CQN31T, was isolated from sediment of Changqiaohai Lake, Yunnan Province, China. Growth occurred at 4-45 °C (optimum, 37 °C), at pH 6.5-9.5 (optimum, pH 8.0) and with 0-1 % (w/v) NaCl (optimum, 0 %). C18 : 1 ω7c/C18 : 1 ω6c and C16 : 0 were the predominant fatty acids. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidyldimethylethanolamine (PME) and one unidentified aminolipid (AL) were the major polar lipids. The G+C content of the genomic DNA was 71.5 %. 16S rRNA gene sequence comparisons indicated that strain CQN31T shared 96.8 % similarity with Roseomonas wooponensis JCM 19527T and 95.9 % with R. terricola EM0302T. Digital DNA-DNA hybridization values between strain CQN31T and Roseomonas stagni DSM 19981T, R. rosea DSM 14916T and R. mucosa NCTC 13291T were 21.0, 19.4 and 19.8 %, respectively. Average amino acid identity and average nucleotide identity values between strain CQN31T and R. stagni DSM 19981T, R. rosea DSM 14916T and R. mucosa NCTC 13291T were 73.7, 63.4 and 61.9 %, and 79.2, 77.1 and 77.5%, respectively. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of strain CQN31T as a representative of a novel species in the genus Roseomonas, for which the name Roseomonas bella sp. nov. is proposed. The type strain is CQN31T (=KCTC 62447T=MCCC 1H00309T).


Assuntos
Sedimentos Geológicos/microbiologia , Lagos/microbiologia , Methylobacteriaceae/classificação , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Methylobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
2.
Artigo em Inglês | MEDLINE | ID: mdl-32537806

RESUMO

BACKGROUND AND AIM: Tubulointerstitial nephritis antigen-like 1 (TINAGL1), as a novel matricellular protein, has been demonstrated to participate in cancer progression, whereas the potential function of TINAGL1 in gastric cancer (GC) remains unknown. METHODS: The expression pattern of TINAGL1 in GC was examined by immunohistochemistry, ELISA, real-time polymerase chain reaction, and Western blot. Correlation between TINAGL1 and matrix metalloproteinases (MMPs) was analyzed by the GEPIA website and Kaplan-Meier plots database. The lentivirus-based TINAGL1 knockdown, CCK-8, and transwell assays were used to test the function of TINAGL1 in vitro. The role of TINAGL1 was confirmed by subcutaneous xenograft, abdominal dissemination, and lung metastasis model. Microarray experiments, ELISA, real-time polymerase chain reaction, and Western blot were used to identify molecular mechanism. RESULTS: TINAGL1 was increased in GC tumor tissues and associated with poor patient survival. Moreover, TINAGL1 significantly promoted GC cell proliferation and migration in vitro as well as facilitated GC tumor growth and metastasis in vivo. TINAGL1 expression in GC cells was accompanied with increasing MMPs including MMP2, MMP9, MMP11, MMP14, and MMP16. GEPIA database revealed that these MMPs were correlated with TINAGL1 in GC tumors and that the most highly expressed MMP was MMP2. Mechanically, TINAGL1 regulated MMP2 through the JNK signaling pathway activation. CONCLUSIONS: Our data highlight that TINAGL1 promotes GC growth and metastasis and regulates MMP2 expression, indicating that TINAGL1 may serve as a therapeutic target for GC.

3.
BMC Cardiovasc Disord ; 20(1): 300, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560699

RESUMO

BACKGROUND: Coronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis. METHODS: We searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software. RESULTS: Six studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223-1.813). Further, MIF -173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365-2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003-1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele. CONCLUSIONS: We found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.

4.
Int J Syst Evol Microbiol ; 70(6): 3679-3685, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32416740

RESUMO

A Gram-stain-negative, rod-shaped (0.2-0.3×1.0-2.4 µm), catalase-positive, oxidase-negative and non-motile bacterium, designated strain RZ26T, was isolated from the marine red algae collected from the coast of Weihai, PR China. Growth of strain RZ26T occurred at 15-33 °C (optimum, 25-28 °C), pH 6.0-9.5 (optimum, pH 7.0-7.5) and 0.5-5.0 % (w/v) NaCl (optimum, 2.0-3.0 %). Resuls of phylogenetic analysis based on 16S rRNA gene sequences showed that strain RZ26T was most closely related to Maribacter spongiicola DSM 25233T (96.2 % sequence similarity), followed by Maribacter forsetii DSM 18668T (96.1 %) and Maribacter vaceletii DSM 25230T (95.4 %). The average nucleotide identity and the average amino acid identity values between strain RZ26T and M. sedimenticola KCTC 12966T, M. spongiicola DSM 25233T, M. vaceletii DSM 25230T and M. forsetii DSM 18668T were 75.6, 76.2, 76.0, 76.7, 64.3, 63.9, 68.6 and 68.0 %, respectively. The digital DNA-DNAhybridization values based on the draft genomes between strain RZ26T and M. sedimenticola KCTC 12966T, M. spongiicola DSM 25233T and M. vaceletii DSM 25230T were 38.0, 35.1 and 37.1 %, respectively. The major fatty acids in strain RZ26T were iso-C17 : 0 3-OH, iso-C15 : 0 and C16 : 1 ω7c/C16 : 1 ω6c. The major respiratory quinone was MK-6. The dominant polar lipid was phosphatidylethanolamine. The DNA G+C content was 38.0 mol%. Phylogenetic analysis shows strain RZ26T fell within a clade comprising species of the genus Maribacter. Polyphasic taxonomy indicates that the isolate represents a novel species of the genus Maribacter, for which the name Maribacter algarum sp. nov. is proposed, with type strain RZ26T (=KCTC 62992T=MCCC 1H00362T).


Assuntos
Flavobacteriaceae/classificação , Filogenia , Rodófitas/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Drug Des Devel Ther ; 14: 1535-1545, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368012

RESUMO

Background: The efficacy of traditional therapeutic methods for liver cancer is unsatisfying because of the poor targeting, and inefficient drug delivery system. A recent study has proven that aptamers, developed through cell-SELEX, could specifically recognize cancer cells and show great potential in the development of a delivery system for anticancer drugs. Purpose: To develop a hepatocellular carcinoma specific aptamer using two kinds of hepatocellular carcinoma cell lines, HepG2 and SMMC-7721, as double targets and a normal hepatocyte, L02, as a negative control cell. Methods: Hepatocellular carcinoma specific aptamer was developed via cell-SELEX. The enrichment of the library was monitored by flow cytometric analysis. The specificity, affinity, and distribution of the candidate aptamer were explored. Further study was carried to assess its potential in drug delivery. Results: The library was enriched after 14 rounds of screening. Candidate aptamer Apt-07S can recognize four kinds of hepatocellular carcinoma cells and show little cell-binding ability to normal cells and four cell lines of different cancer types, revealing a high specificity of Apt-07S. Confocal imaging showed that Apt-07S distributed both on the surface and in the cytoplasm of the two target cells. Moreover, an anti-sense nucleotide to gene Plk1 (ASO-Plk1) was connected at the 3' end of Apt-07S to form an integrated molecule (Apt-07S-ASO-Plk1); the functional analysis indicated that the structure of Apt-07S may help ASO-Plk1 enter the cancer cells. Conclusion: The study indicates that Apt-07S can specifically target HCC and may have potential in the delivery of anticancer drugs.

6.
Int J Syst Evol Microbiol ; 70(6): 3588-3596, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32453683

RESUMO

A Gram-stain-negative, non-motile, fine rod or short filament shaped, jacinth pigmented bacterium, designated strain WDS2C27T, was isolated from a marine solar saltern in Wendeng, Weihai, PR China (37°31'5″ N, 122°1'47″ E). Growth of WDS2C27T occurred at 20-42 °C (optimum 37 °C) and pH 6.5-8.5 (optimal pH 7.0-8.0). Optimal growth occurred in modified marine broth containing 6 % (w/v) NaCl. The major polar lipids in WDS2C27T were phosphatidylethanolamine, two unidentified aminolipids and one unidentified lipid. The major respiratory quinone of WDS2C27T was MK-6. The dominant fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The DNA G+C content was 35.0 mol%. The nucleotide sequence of the 16S rRNA gene indicated that the most closely related strain was Psychroflexus planctonicus X15M-8T (92.0 % over 1452 bp). WDS2C27T showed 60.7 % average amino acid identity, 55.6 % percentage of conserved proteins, 75.0 % average nucleotide identity and 13.1 % digital DNA-DNA hybridization identity with the type species of the genus Psychroflexus, Psychroflexus torquis ATCC 700755T. The phenotypic and genotypic properties and phylogenetic inference indicated that WDS2C27T could be assigned to a novel species within a novel genus, for which the name Mesohalobacter halotolerans gen. nov., sp. nov. is proposed. Strain WDS2C27T (=MCCC 1H00133T=KCTC 52044T) is the type strain.


Assuntos
Flavobacteriaceae/classificação , Filogenia , Salinidade , Microbiologia da Água , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
7.
Int J Syst Evol Microbiol ; 70(6): 3740-3748, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32441611

RESUMO

A Gram-stain-negative, aerobic, gliding, rod-shaped (0.2-0.5×1.0-13.0 µm) and yellow-pigmented bacterium, designated PLHSN227T, was isolated from seawater collected near the coast of Yantai, PR China. PLHSN227T was found to grow at 15-37 °C (optimum, 28-30 °C) and pH 6.0-8.5 (optimum, 6.5-7.5) in the presence of 2-14 % (w/v) NaCl (optimum, 5.0 %). Phylogenetic analysis of the 16S rRNA gene sequences revealed that PLHSN227T represented a member of the family Flavobacteriaceae and exhibited the highest sequence similarity (94.6 %) to the type strain Salegentibacter holothuriorum NBRC 100249T. The chemotaxonomic analysis revealed that the sole respiratory quinone was menaquinone 6 (MK-6) and the major fatty acids included C19 : 0ω8c cyclo, iso-C15 : 0, anteiso-C15 : 0, C18 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids included phosphatidylethanolamine, one unidentified aminolipid and two unidentified lipids. The DNA G+C content of PLHSN227T was 35.6 mol%. PLHSN227T showed the highest average amino acid identity value of 67.2 %, the average nucleotide identity value of 75.6 and 14.5 % digital DNA-DNA hybridization identity with Mesonia algae DSM 15361T. According to the phylogenetic data, PLHSN227T formed a distinct clade in the phylogenetic tree. On the basis of phenotypic, chemotaxonomic and phylogenetic data, it is considered that PLHSN227T represents a novel genus within the family Flavobacteriaceae, for which the name Haloflavibacter putidus gen. nov., sp. nov. is proposed. The type strain is PLHSN227T (=KCTC 72159T=MCCC 1H00371T).


Assuntos
Flavobacteriaceae/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
8.
Cell Death Dis ; 11(3): 189, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184393

RESUMO

Adrenomedullin (ADM) is a multifunctional peptide that is expressed by many surface epithelial cells, but its relevance to Helicobacter pylori (H. pylori)-induced gastritis is unknown. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice. In H. pylori-infected human gastric mucosa, ADM expression was positively correlated with the degree of gastritis; accordingly, blockade of ADM resulted in decreased inflammation within the gastric mucosa of H. pylori-infected mice. During H. pylori infection, ADM production was promoted via PI3K-AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterized by the increased IFN-γ-producing T cells, whose differentiation was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-γ-producing T-cell responses, thereby contributing to the development of H. pylori-associated gastritis. Accordingly, blockade of IFN-γ or knockout of IFN-γ decreased inflammation within the gastric mucosa of H. pylori-infected mice. This study identifies a novel regulatory network involving H. pylori, gastric epithelial cells, ADM, macrophages, T cells, and IFN-γ, which collectively exert a pro-inflammatory effect within the gastric microenvironment.

9.
FASEB J ; 34(1): 1169-1181, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914631

RESUMO

BHLHE40, a member of the basic helix-loop-helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)-associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori-infected GECs express BHLHE40 via cagA-ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein-activated p-STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA-BHLHE40-CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Quimiocina CXCL12/metabolismo , Células Epiteliais/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/metabolismo , Proteínas de Homeodomínio/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Linfócitos T CD4-Positivos/citologia , Núcleo Celular/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/metabolismo , Regulação da Expressão Gênica , Helicobacter pylori , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Estômago/microbiologia , Regulação para Cima
10.
Int J Syst Evol Microbiol ; 70(3): 1555-1561, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31860427

RESUMO

A Gram-stain-positive, facultatively anaerobic bacterium, strain JDX10T, was isolated from a soil sample of Fildes Peninsula, Antarctica. Cells of the strain were irregular rod-shaped and non-motile. Cells grew at 4-40 °C (optimum, 28 °C), at pH 6.0-9.0 (optimum, 7.5) and with 0.0-3.0 % (w/v) NaCl (optimum, 1.0 %). According to phylogenetic analysis based on 16S rRNA gene sequences, strain JDX10T was associated with the genus Tessaracoccus, and showed highest similarities to Tessaracoccus rhinocerotis CCTCC AB 2013217T (97.2 %), Tessaracoccus flavescens SST-39T (96.9 %) and Tessaracoccus terricola JCM 32157T (96.9 %). The average nucleotide identity scores of strain JDX10T to T. rhinocerotis CCTCC AB 2013217T and T. bendigoensis JCM 13525T were 74.8 and 73.3 %, respectively and the Genome-to-Genome Distance Calculator scores were 19.2 and 18.7 %, respectively. The major (>10.0 %) cellular fatty acid was anteiso-C15 : 0. The predominant isoprenoid quinone was MK-10(H4). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The phylogenetic analysis and physiological and biochemical data showed that strain JDX10T should be classified as representing a novel species in the genus Tessaracoccus, for which the name Tessaracoccus antarcticus sp. nov. is proposed. The type strain is JDX10T (=MCCC 1H00351T=KCTC 49242T).


Assuntos
Filogenia , Propionibacteriaceae/classificação , Rodopsina , Microbiologia do Solo , Regiões Antárticas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Glicolipídeos/química , Fosfolipídeos/química , Propionibacteriaceae/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/análogos & derivados , Ubiquinona/química
11.
Chem Commun (Camb) ; 55(79): 11864-11867, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528888

RESUMO

A switchable regioselectivity in C-H thiolation reaction by simply swapping the counteranions of TMS is reported here for the first time. An exclusive C3-H thiolation of indoles with sodium arylsulfinates was achieved in the presence of TMSCl as a promoter. In contrast, with the use of TMSOTf instead of TMSCl under otherwise identical conditions, a regiospecific C2-H thiolation of indoles was realized with the same set of substrates.

12.
PLoS One ; 14(9): e0222340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509580

RESUMO

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development.


Assuntos
Hormônio do Crescimento/genética , MicroRNAs/genética , Hormônios Adeno-Hipofisários/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular , Expressão Gênica , Regulação da Expressão Gênica/genética , Hormônio do Crescimento/metabolismo , Masculino , Hipófise/metabolismo , Adeno-Hipófise/metabolismo , Hormônios Adeno-Hipofisários/metabolismo , Cultura Primária de Células , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transfecção
13.
Zhongguo Zhong Yao Za Zhi ; 44(10): 1989-2008, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355552

RESUMO

Polygonatum plants are perennial plants of Liliaceae. There are about 60 species reported at home and abroad,32 species in China,mainly distributed in the north temperate zone. Their main chemical components are steroidal saponins,polysaccharides,flavonoids,alkaloids,etc. They have anti-aging,anti-tumor,immunomodulation,antibacterial,antiviral,hypoglycemic and blood lipid effects. With the development of health industry,Polygonati Rhizome used as medicine and food has attracted great attention in recent years,and has become a research hotspot. However,the material basis of its efficacy is unclear and the product quality is uneven,which seriously limited the rapid upgrading of the industry. This review summarizes Polygonatum plants system classification,the chemical composition and pharmacological activity to provide theoretical basis for the development and utilization of Polygonatum plants.


Assuntos
Compostos Fitoquímicos/farmacologia , Polygonatum/química , China , Compostos Fitoquímicos/química , Plantas Medicinais/química , Rizoma/química
14.
Org Biomol Chem ; 17(19): 4789-4800, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31033985

RESUMO

An unexpected time-controlled highly selective C3- or C2-sulfinylation of pyrroles with sulfinamides is reported for the first time. The sulfinylation of indoles with sulfinamides using this protocol is oxidant-free and can be performed under obviously more feasible conditions (1.2 equiv. of indoles, 10 min) in comparison with the precedent procedure (3-20 equiv. of indoles, 16-18 h, ammonium persulfate as oxidant, hv). A variety of functional groups were tolerated, and various C2-thioindoles and C2/3-thiopyrroles were obtained in moderate to excellent yields.

15.
Sci Adv ; 5(4): eaau6547, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30949574

RESUMO

The interaction between gastric epithelium and immune response plays key roles in H. pylori-associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in H. pylori infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by H. pylori and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with H. pylori colonization and the severity of gastritis, and mouse MMP-10 from non-BM-derived cells promoted bacteria colonization and inflammation. H. pylori colonization and inflammation were attenuated in IL-22-/-, MMP-10-/-, and IL-22-/-MMP-10-/- mice. MMP-10-associated inflammation is characterized by the influx of CD8+ T cells, whose migration is induced via MMP-10-CXCL16 axis by gastric epithelial cells. Under the influence of MMP-10, Reg3a, E-cadherin, and zonula occludens-1 proteins decrease, resulting in impaired host defense and increased H. pylori colonization. Our results suggest that MMP-10 facilitates H. pylori persistence and promotes gastritis.


Assuntos
Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Metaloproteinase 10 da Matriz/metabolismo , Animais , Biomarcadores , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Quimiocina CXCL16/metabolismo , Modelos Animais de Doenças , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Expressão Gênica , Infecções por Helicobacter/genética , Humanos , Interleucinas/metabolismo , Metaloproteinase 10 da Matriz/genética , Camundongos , Camundongos Knockout , Modelos Biológicos
16.
FASEB J ; 33(4): 5018-5033, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30596522

RESUMO

Cathepsin C (CtsC) functions as a central coordinator for activation of many serine proteases in immune cells. However, CtsC expression in gastric epithelial cells and its role in Helicobacter pylori infection remain unclear. Real-time PCR, Western blot, and immunohistochemistry analyses identified that CtsC was decreased in gastric mucosa of H. pylori-infected patients and mice. Isolated gastric epithelial cells and cell lines were stimulated with H. pylori and/or TGF-ß1 showed that down-regulation of CtsC in gastric epithelial cells largely depended on H. pylori cagA via Src/ERK and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways, and the effect could be synergistically augmented by TGF-ß1 in an autocrine manner. In human gastric mucosa, CtsC expression was negatively correlated with bacteria colonization; accordingly, provision of exogenous active CtsC overwhelmed H. pylori persistence in gastric mucosa of mice. In the presence of active CtsC, isolated human neutrophils activated via NF-κB pathway with augmented bactericidal capacity in vitro. We also found that neutrophils activated and cleared bacteria in active CtsC-injected mice and that there was no bactericidal capacity in mice that were simultaneously neutrophil-depleted by Ly6G antibody. Our findings identified a mechanism that H. pylori abrogate CtsC to impair neutrophil activation and to ensure persistence in gastric mucosa. Efforts to enable and boost this neutrophil activation pathway by active CtsC may therefore become valuable strategies in treating H. pylori infection.-Liu, Y. G., Teng, Y. S., Cheng, P., Kong, H., Lv, Y. P., Mao, F. Y., Wu, X. L., Hao, C. J., Chen, W., Yang, S. M., Zhang, J. Y., Peng, L. S., Wang, T. T., Han, B., Ma, Q., Zou, Q. M., Zhuang, Y. Abrogation of cathepsin C by Helicobacter pylori impairs neutrophil activation to promote gastric infection.


Assuntos
Catepsina C/metabolismo , Mucosa Gástrica/microbiologia , Helicobacter pylori/patogenicidade , Ativação de Neutrófilo/fisiologia , Animais , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Infecções por Helicobacter/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Fagocitose/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
17.
Cell Death Dis ; 10(2): 79, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30692510

RESUMO

Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found that gastric IL-17RB mRNA and protein were decreased in gastric mucosa of both patients and mice infected with H. pylori. In vitro experiments show that IL-17RB expression was down regulated via PI3K/AKT pathway on gastric epithelial cells (GECs) stimulated with H. pylori in a cagA-involved manner, while in vivo studies showed that the effect was partially dependent on cagA expression. IL-17E was also decreased during the early-phase of H. pylori infection, and provision of exogenous IL-17E resulted in increased CD11b+CD11c- myeloid cells accumulation and decreased bacteria colonization within the gastric mucosa. In the early-phase of H. pylori infection, IL-17E-IL-17RB promoted gastric epithelial cell-derived CXCL1/2/5/6 to attract CD11b+CD11c- myeloid cells, and also contributed to host defense by promoting the production of antibacterial protein Reg3a. This study defines a negative regulatory network involving IL-17E, GECs, IL-17RB, CD11b+CD11c- myeloid cells, and Reg3a in the early-phase of H. pylori infection, which results in an impaired host defense within the gastric microenvironment, suggesting IL-17RB as a potential early intervening target in H. pylori infection.


Assuntos
Antígeno CD11b/imunologia , Antígeno CD11c/imunologia , Mucosa Gástrica/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/isolamento & purificação , Células Mieloides/imunologia , Receptores de Interleucina-17/imunologia , Animais , Antígenos CD11/biossíntese , Antígenos CD11/imunologia , Antígeno CD11b/biossíntese , Antígeno CD11b/sangue , Antígeno CD11c/biossíntese , Infecções por Helicobacter/sangue , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Receptores de Interleucina-17/biossíntese , Receptores de Interleucina-17/genética
18.
Cell Death Dis ; 9(10): 1034, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305610

RESUMO

Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mast cell levels increased with tumor progression and independently predicted reduced overall survival. Tumor-derived adrenomedullin (ADM) induced mast cell degranulation via PI3K-AKT signaling pathway, which effectively promoted the proliferation and inhibited the apoptosis of GC cells in vitro and contributed to the growth and progression of GC tumors in vivo, and the effect could be reversed by blocking interleukin (IL)-17A production from these mast cells. Our results illuminate a novel protumorigenic role and associated mechanism of mast cells in GC, and also provide functional evidence for these mast cells to prevent, and to treat this immunopathogenesis feature of GC.


Assuntos
Adrenomedulina/metabolismo , Mastócitos/metabolismo , Mastócitos/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Exocitose/fisiologia , Feminino , Humanos , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Estômago/patologia , Microambiente Tumoral/fisiologia
19.
J Immunol Res ; 2018: 6248590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30255106

RESUMO

Natural killer (NK) cell activity is influenced by a complex integration of signaling pathways activated downstream of both activating and inhibitory surface receptors. The tumor microenvironment can suppress NK cell activity, and there is a great clinical interest in understanding whether modulating tumor-mediated NK cell suppression and/or boosting preexisting NK cell numbers in cancer patients is therapeutically viable. To this light, we characterized the surface receptor phenotypes of peripheral blood NK cells and examined their clinical relevance to human gastric cancer (GC). We found that the proportion of peripheral blood NK cells which expressed the activating receptors NKp30, NKp46, NKG2D, and DNAM-1 was significantly decreased in GC patients compared to healthy donors, and that this decrease was positively associated with tumor progression. At the same time, plasma TGF-ß1 concentrations were significantly increased in GC patients and negatively correlated with the proportion of NKp30, NKp46, NKG2D, and DNAM-1 expressing NK cells. Furthermore, TGF-ß1 significantly downregulated the expression of NKp30, NKp46, NKG2D, and DNAM-1 on NK cells in vitro, and the addition of galunisertib, an inhibitor of the TGF-ß receptor subunit I, reversed this downregulation. Altogether, our data suggest that the decreased expression of activating receptors NKp30, NKp46, NKG2D, and DNAM-1 on peripheral blood NK cells is positively associated with GC progression, and that TGF-ß1-mediated NK cell suppression may be a therapeutically targetable characteristic of GC.


Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo , Neoplasias Gástricas/imunologia , Adulto , Idoso , Carcinogênese , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Fator de Crescimento Transformador beta1/metabolismo , Evasão Tumoral
20.
Cell Death Dis ; 9(7): 763, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29988030

RESUMO

Myeloid-derived suppressor cells (MDSCs) are a prominent component of the pro-tumoral response. The phenotype of and mechanisms used by MDSCs is heterogeneous and requires more precise characterization in gastric cancer (GC) patients. Here, we have identified a novel subset of CD45+CD33lowCD11bdim MDSCs in the peripheral blood of GC patients compared to healthy individuals. CD45+CD33lowCD11bdim MDSCs morphologically resembled neutrophils and expressed high levels of the neutrophil marker CD66b. Circulating CD45+CD33lowCD11bdim MDSCs effectively suppressed CD8+ T cells activity through the inhibition of CD8+ T cell proliferation and interferon-γ (IFN-γ) and granzyme B (GrB) production. The proportion of CD45+CD33lowCD11bdim MDSCs also negatively correlated with the proportion of IFN-γ+CD8+ T cell in the peripheral blood of GC patients. GC patient serum-derived IL-6 and IL-8 activated and induced CD45+CD33lowCD11bdim MDSCs to express arginase I via the PI3K-AKT signaling pathway. This pathway contributed to CD8+ T cell suppression as it was partially rescued by the blockade of the IL-6/IL-8-arginase I axis. Peripheral blood CD45+CD33lowCD11bdim MDSCs, as well as IL-6, IL-8, and arginase I serum levels, positively correlated with GC progression and negatively correlated with overall patient survival. Altogether, our results highlight that a subset of neutrophilic CD45+CD33lowCD11bdim MDSCs is functionally immunosuppressive and activated via the IL-6/IL-8-arginase I axis in GC patients.


Assuntos
Arginase/metabolismo , Antígeno CD11b/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Células Supressoras Mieloides/metabolismo , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Arginase/genética , Western Blotting , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
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