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1.
Arch Virol ; 164(11): 2793-2797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31440811

RESUMO

The DC-SIGN glycoprotein is responsible for the initial adhesion of dengue virus (DENV) to immune cells by the carbohydrate recognition domain (CRD). There are thirteen soluble and membrane-bound DC-SIGN isoforms, but the role of soluble isoforms in the DENV internalization process is not known. Five isoforms with an altered or absent CRD were identified, and three different soluble isoforms were used to confirm the interactions with mannose residues. The results show the loss of binding ability of one soluble isoform and binding ability of two of them. All of them will be used to verify their role in the DENV internalization process.


Assuntos
Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Vírus da Dengue/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Manose/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Ligação Viral , Internalização do Vírus , Sequência de Aminoácidos , Sequência de Bases , Dengue/virologia , Vírus da Dengue/genética , Ligantes , Ligação Proteica/genética , Isoformas de Proteínas/genética
2.
J Biol Regul Homeost Agents ; 33(3): 675-685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189490

RESUMO

Endometrial cells undergo very specific changes associated with reproductive processes. Cells prepare for embryo development by increasing their volume. Then, if fertilization fails, endometrial cells are liable for apoptosis, preparing new cells that are ready for subsequent processes related to the possibility of embryo implantation and the development of pregnancy. PTX3 and TNFAIP6 are absent or reduced in cultured COCs, resulting in a functional change in COC in vitro. In this work, we want to check how PTX3, HAS2 and TNFAIP6 behave in luminal epithelium primary cell culture. Cells obtained during slaughter from porcine specimens were cultured primarily in vitro for 7 days. Their proliferation patterns were then analysed using RTCA, with the expression of genes of interest evaluated with the use of immunofluorescence and RT-qPCR. The results of these changes in the expression of the genes of interest were analysed on each of the seven days of the porcine luminal primary cell culture. Our study showed the increased level of PTX3, HAS2 and TN¬FAIP6 expression at the same hours of primary culture. Rt-qPCR showed a higher level of expression of the PTX3 gene in the first 72 h, at the end of the lag phase (in the phase of stasis in which the cells adapt to the new environment and often die). In contrast, TNFAIP6 expression increases about 96 hours when the cells are in the full log phase (logarithmic phase growth) and continue this trend in the plateau phase. We did not observe such drastic changes in the HAS2 expression pattern, which leads us to hypothesize that PTX3 and TNFAIP6 are designed to maintain a constant level of HAS2 in the cell throughout its lifetime. The obtained results could become a point of reference for further in vivo and clinical research.


Assuntos
Proteína C-Reativa/genética , Moléculas de Adesão Celular/genética , Endométrio/citologia , Células Epiteliais/citologia , Hialuronan Sintases/genética , Componente Amiloide P Sérico/genética , Animais , Proliferação de Células , Feminino , Cultura Primária de Células , Suínos
3.
Adv Clin Exp Med ; 28(7): 899-905, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31066244

RESUMO

BACKGROUND: The relationship of diffusely adherent Escherichia coli (DAEC) with pediatric inflammatory bowel disease (IBD) has not been previously studied. Diffusely adherent E. coli are a common cause of long-lasting childhood diarrhea and we postulated that they may induce inflammation of the intestinal mucosa, contributing to the development of IBD in susceptible children. OBJECTIVES: The aim of the study was to investigate the relationship between DAEC and pediatric IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Diffusely adherent E. coli isolates were also assessed regarding their pathogenicity. MATERIAL AND METHODS: Diffusely adherent E. coli were screened among 130 E. coli strains isolated from intestinal biopsy specimens from 26 children with IBD using polymerase chain reaction (PCR) with primers specific to the pathotype and adherence assays to HEp-2 cells. Diffusely adherent E. coli were further analyzed for their ability to adhere to and invade polarized Caco-2 cells. The immunomodulatory effect of DAEC on the secretion of tumor necrosis factor α (TNF-α) by human monocyte-derived macrophages (MDM) was assessed using an immunoenzymatic assay. RESULTS: Diffusely adherent E. coli were recovered from 18 (69.2%) of the 26 intestinal biopsy specimens from both CD and UC patients. Most DAEC isolates carried AfaE3 adhesin, adhered to and were internalized by Caco-2 cells, and induced secretion of elevated levels of TNF-α. CONCLUSIONS: The study demonstrated the internalization of DAEC by intestinal epithelial cells and their ability to induce secretion of increased level of TNF-α in a Caco-2/macrophage compartmentalized culture. This indicated that the pathovar should be considered a pathobiont inducing inflammation of the intestinal mucosa in pediatric patients with IBD.


Assuntos
Aderência Bacteriana , Moléculas de Adesão Celular/metabolismo , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/isolamento & purificação , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Adesinas de Escherichia coli , Células CACO-2 , Moléculas de Adesão Celular/genética , Criança , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/imunologia , Doença de Crohn/epidemiologia , Doença de Crohn/imunologia , Escherichia coli/genética , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/imunologia , Polônia/epidemiologia , Prevalência
4.
Genes Cells ; 24(7): 496-510, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31124270

RESUMO

In the Drosophila brain, neurons form genetically specified synaptic connections with defined neuronal targets. It is proposed that each central nervous system neuron expresses specific cell surface proteins, which act as identification tags. Through an RNAi screen of cell surface molecules in the Drosophila visual system, we found that the cell adhesion molecule Klingon (Klg) plays an important role in repressing the ectopic formation of extended axons, preventing the formation of excessive synapses. Cell-specific manipulation of klg showed that Klg is required in both photoreceptors and the glia, suggesting that the balanced homophilic interaction between photoreceptor axons and the glia is required for normal synapse formation. Previous studies suggested that Klg binds to cDIP and our genetic analyses indicate that cDIP is required in glia for ectopic synaptic repression. These data suggest that Klg play a critical role together with cDIP in refining synaptic specificity and preventing unnecessary connections in the brain.


Assuntos
Moléculas de Adesão Celular/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Proteínas do Olho/metabolismo , Neuroglia/fisiologia , Células Fotorreceptoras de Invertebrados/fisiologia , Sinapses/fisiologia , Vias Visuais , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/fisiologia , Axônios/fisiologia , Moléculas de Adesão Celular/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas do Olho/genética , Feminino
5.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075901

RESUMO

The alveolar epithelial cells represent an important part of the alveolar barrier, which is maintained by tight junction proteins, particularly JAM-A, occludin, and claudin-18, which regulate paracellular permeability. In this study, we report on a strong increase in epithelial JAM-A expression in P2X7 receptor knockout mice when compared to the wildtype. Precision-cut lung slices of wildtype and knockout lungs and immortal epithelial lung E10 cells were treated with bleomycin, the P2X7 receptor inhibitor oxATP, and the agonist BzATP, respectively, to evaluate early changes in JAM-A expression. Biochemical and immunohistochemical data showed evidence for P2X7 receptor-dependent JAM-A expression in vitro. Inhibition of the P2X7 receptor using oxATP increased JAM-A, whereas activation of the receptor decreased the JAM-A protein level. In order to examine the role of GSK-3ß in the expression of JAM-A in alveolar epithelial cells, we used lithium chloride for GSK-3ß inhibiting experiments, which showed a modulating effect on bleomycin-induced alterations in JAM-A levels. Our data suggest that an increased constitutive JAM-A protein level in P2X7 receptor knockout mice may have a protective effect against bleomycin-induced lung injury. Bleomycin-treated precision-cut lung slices from P2X7 receptor knockout mice responded with a lower increase in mRNA expression of JAM-A than bleomycin-treated precision-cut lung slices from wildtype mice.


Assuntos
Moléculas de Adesão Celular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Células Epiteliais Alveolares/metabolismo , Animais , Bleomicina , Moléculas de Adesão Celular/genética , Camundongos , Agonistas do Receptor Purinérgico P2X/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/genética , Receptores Purinérgicos P2X7/deficiência
6.
Adv Exp Med Biol ; 1132: 7-20, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037620

RESUMO

Although many studies have described the role of periostin in various diseases, the functions of periostin derived from alternative splicing and proteinase cleavage at its C-terminus remain unknown. Further experiments investigating the periostin structures that are relevant to diseases are essential for an in-depth understanding of their functions, which would accelerate their clinical applications by establishing new approaches for curing intractable diseases. Furthermore, this understanding would enhance our knowledge of novel functions of periostin related to stemness and response to mechanical stress .


Assuntos
Processamento Alternativo , Moléculas de Adesão Celular/genética , Humanos
7.
Cancer Biother Radiopharm ; 34(4): 258-263, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31070482

RESUMO

Background: Downregulation of LncRNA LINC-PINT has been observed in different types of cancer cells, indicating its role as a tumor suppressor. Materials and Methods: Expression of LINC-PINT and miRNA-21 in tumor tissues and adjacent healthy tissues of 56 patients with osteosarcoma was detected by real-time quantitative PCR. Correlations between expression levels of LncRNA LINC-PINT and miRNA-21 were analyzed by Pearson's correlation coefficient. Results: In this study, we found that LncRNA LINC-PINT was inhibited, whereas miRNA-21 was promoted in tumor tissues than in adjacent healthy tissues of patients with osteosarcoma. Expression levels of LncRNA LINC-PINT were affected by both tumor size and tumor metastasis. LncRNA LINC-PINT and miRNA-21 were significantly and reversely correlated in both tumor cells and adjacent healthy tissues. LncRNA LINC-PINT overexpression led to downregulated miRNA-21 expression in cancer cells, whereas miRNA-21 overexpression did not significantly affect LINC-PINT expression. Overexpression of LncRNA LINC-PINT inhibited whereas miRNA-21 overexpression promoted cancer cell proliferation, migration, and invasion. In addition, miRNA-21 overexpression partially rescued the inhibited cell proliferation, migration, and invasion mediated by LncRNA LINC-PINT overexpression. Conclusion: Therefore, LncRNA LINC-PINT may inhibit cancer cell proliferation, invasion, and migration in osteosarcoma by downregulating miRNA-21.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/genética , RNA Longo não Codificante/metabolismo , Adolescente , Adulto , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Carga Tumoral/genética , Regulação para Cima , Adulto Jovem
8.
Int J Oncol ; 54(6): 1955-1968, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081051

RESUMO

Studies have rarely been conducted on the role of miRNAs in prostate cancer (PCa) cell progression by directly targeting MTDH, at least to the best of our knowledge. Thus, the present study aimed to identify miRNAs closely related with metadherin (MTDH) and to determine their roles in PCa. For this purpose, the expression levels of MTDH in PCa tissues and cell lines were examined by RT­qPCR, immunohistochemistry and western blot analysis. By cell transfection, MTDH was either overexpressed in the normal prostate epithelial cell lines or silenced in tumor cell lines to determine cell viability, invasion and migration. Bioinformatics analysis, RT­qPCR, western blot analysis, dual­luciferase reporter assay and MTT assay were performed to identify direct the target of MTDH and to examine tumor cell viability. Rescue experiments using the PC­3 and LNCaP cells were carried out by MTT assay, scratch wound assay, Transwell assay, RT­qPCR and western blot analysis. Experiments were also conducted using 46 PCa human cancer and adjacent tissues, as wells as on 501 cases of PCa from the TCGA database. It was confirmed that the overexpression of MTDH was associated with a poor prognosis of patients. The overexpression of MTDH was found to promote the viability, invasion and migration of PCa cells. miR­145­5p and miR­145­3p identified from 16 miRNAs were found to be closely related to PCa and to be the targets of MTDH. Both these miRNAs were found to significantly suppress the growth and metastasis of PCa cells by negatively regulating the expression of MTDH. On the whole, the findings of this study demonstrate that MTDH functions as an oncogene in PCa and the inhibition of MTDH by miR­145­5p or miR­145­3p suppressed the growth and metastasis of PCa cells. The miR­145­5p/MTDH and miR­145­3p/MTDH pathways may thus become novel treatment targets for PCa.


Assuntos
Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , MicroRNAs/genética , Neoplasias da Próstata/metabolismo , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Análise de Sobrevida , Regulação para Cima
9.
Nat Commun ; 10(1): 2246, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113950

RESUMO

Epigenetic control of enhancers alters neuronal functions and may be involved in Alzheimer's disease (AD). Here, we identify enhancers in neurons contributing to AD by comprehensive fine-mapping of DNA methylation at enhancers, genome-wide. We examine 1.2 million CpG and CpH sites in enhancers in prefrontal cortex neurons of individuals with no/mild, moderate, and severe AD pathology (n = 101). We identify 1224 differentially methylated enhancer regions; most of which are hypomethylated at CpH sites in AD neurons. CpH methylation losses occur in normal aging neurons, but are accelerated in AD. Integration of epigenetic and transcriptomic data demonstrates a pro-apoptotic reactivation of the cell cycle in post-mitotic AD neurons. Furthermore, AD neurons have a large cluster of significantly hypomethylated enhancers in the DSCAML1 gene that targets BACE1. Hypomethylation of these enhancers in AD is associated with an upregulation of BACE1 transcripts and an increase in amyloid plaques, neurofibrillary tangles, and cognitive decline.


Assuntos
Doença de Alzheimer/patologia , Disfunção Cognitiva/patologia , Elementos Facilitadores Genéticos , Neurônios/patologia , Córtex Pré-Frontal/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Moléculas de Adesão Celular/genética , Disfunção Cognitiva/genética , Estudos de Coortes , Ilhas de CpG/genética , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/citologia , Regulação para Cima
10.
Pathol Res Pract ; 215(5): 1038-1048, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30975489

RESUMO

BACKGROUND AND OBJECTIVE: The underlying molecular mechanisms of gastric cancer (GC) have yet not been investigated clearly. In this study, we aimed to identify hub genes involved in the pathogenesis and prognosis of GC. METHODS: We integrated five microarray datasets from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between GC and normal samples were analyzed with limma package. Gene ontology (GO) and KEGG enrichment analysis were performed using DAVID. Then we established the protein-protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING). The prognostic analysis of hub genes were performed through Gene Expression Profiling Interactive Analysis (GEPIA). Additionally, we used real-time quantitative PCR to validate the expression of hub genes in 5 pairs of tumor tissues and corresponding adjacent tissues. Finally, the candidate small molecules as potential drugs to treat GC were predicted in CMap database. RESULTS: Through integrating five microarray datasets, a total of 172 overlap DEGs were detected including 79 up-regulated and 93 down-regulated genes. Biological process analysis of functional enrichment showed these DEGs were mainly enriched in digestion, collagen fibril organization and cell adhesion. Signaling pathway analysis indicated that these DEGs played an vital in ECM-receptor interaction, focal adhesion and metabolism of xenobiotics by cytochrome P450. Protein-protein interaction network among the overlap DEGs was established with 124 nodes and 365 interactions. Three DEGs with high degree of connectivity (NID2, COL4A1 and COL4A2) were selected as hub genes. The GEPIA database confirmed that overexpression levels of hub genes were significantly associated with worse survival of patients. Finally, the 20 most significant small molecules were obtained based on CMap database and spiradoline was the most promising small molecule to reverse the GC gene expression. CONCLUSIONS: Our results indicated that NID2, COL4A1 and COL4A2 could be the potential novel biomarkers for GC diagnosis prognosis and the promising therapeutic targets. The present study may be crucial to understanding the molecular mechanism of GC initiation and progression.


Assuntos
Biomarcadores Tumorais/análise , Moléculas de Adesão Celular/genética , Colágeno Tipo IV/genética , Neoplasias Gástricas/genética , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Conjuntos de Dados como Assunto , Progressão da Doença , Descoberta de Drogas/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias Gástricas/patologia , Transcriptoma
11.
PLoS Genet ; 15(4): e1008077, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30969964

RESUMO

The role of ribosomal protein S6 (rpS6) phosphorylation in mRNA translation remains poorly understood. Here, we reveal a potential role in modulating the translation rate of chemokine (C-X-C motif) ligand 8 (CXCL8 or Interleukin 8, IL8). We observed that more CXCL8 protein was being secreted from less CXCL8 mRNA in primary macrophages and macrophage-like HL-60 cells relative to other cell types. This correlated with an increase in CXCL8 polyribosome association, suggesting an increase in the rate of CXCL8 translation in macrophages. The cell type-specific expression levels were replicated by a CXCL8- UTR-reporter (Nanoluc reporter flanked by the 5' and 3' UTR of CXCL8). Mutations of the CXCL8-UTR-reporter revealed that cell type-specific expression required: 1) a 3' UTR of at least three hundred bases; and 2) an AU base content that exceeds fifty percent in the first hundred bases of the 3' UTR immediately after the stop codon, which we dub AU-rich proximal UTR sequences (APS). The 5' UTR of CXCL8 enhanced expression at the protein level and conferred cell type-specific expression when paired with a 3' UTR. A search for other APS-positive mRNAs uncovered TNF alpha induced protein 6 (TNFAIP6), another mRNA that was translationally upregulated in macrophages. The elevated translation of APS-positive mRNAs in macrophages coincided with elevated rpS6 S235/236 phosphorylation. Both were attenuated by the ERK1/2 signaling inhibitors, U0126 and AZD6244. In A549 cells, rpS6 S235/236 phosphorylation was induced by TAK1, Akt or PKA signaling. This enhanced the translation of the CXCL8-UTR-reporters. Thus, we propose that the induction of rpS6 S235/236 phosphorylation enhances the translation of mRNAs that contain APS motifs, such as CXCL8 and TNFAIP6. This may contribute to the role of macrophages as the primary producer of CXCL8, a cytokine that is essential for immune cell recruitment and activation.


Assuntos
Interleucina-8/biossíntese , Interleucina-8/genética , Proteína S6 Ribossômica/metabolismo , Células A549 , Elementos Ricos em Adenilato e Uridilato , Sequência de Bases , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Fator de Iniciação 4E em Eucariotos/metabolismo , Células HL-60 , Humanos , Sistema de Sinalização das MAP Quinases , Macrófagos/imunologia , Macrófagos/metabolismo , Modelos Biológicos , Mutagênese , Fosforilação , Polirribossomos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína S6 Ribossômica/química , Proteína S6 Ribossômica/genética , Regiões não Traduzidas
12.
Biomed Res Int ; 2019: 9845709, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984789

RESUMO

Aims: To investigate whether bone marrow derived mesenchymal stromal cells (BMSC) have ameliorated ischemia/reperfusion injury-induced acute kidney injury (IRI-AKI) via tumor necrosis factor-inducible gene 6 protein (TSG-6) and how TSG-6 exerted this effect. Methods: We used lentiviral vectors of short hairpin RNA (shRNA) targeting TSG-6 gene to silence TSG-6 in BMSC. And TSG-6-silenced BMSC were administrated into IRI-AKI rats. Then we analyzed serum creatinine (Scr) and renal histology of IRI-AKI rats treated with BMSC after different pretreatments. Furthermore, we explored the effect of TSG-6 on renal tubular epithelial cells proliferation in vivo and in vitro assays. Results: The Scr levels of IRI-AKI rats treated with BMSC (73.5±7.8 µmol/L) significantly decreased compared to those of IRI-AKI rats treated without BMSC (392.5±24.8 µmol/L, P<0.05) or with DMEM (314.0±19.8 µmol/L, P<0.05). Meanwhile, the renal tissue injury in IRI-AKI rats treated with BMSC improved markedly. However, the Scr levels of IRI-AKI rats treated with TSG-6-silenced BMSC (265.1±21.2 µmol/L) significantly increased compared to those with BMSC (74.0±8.5 µmol/L, P<0.05). The proportion of Ki67-positive cells was reduced in IRI-AKI rats treated with TSG-6-silenced BMSC compared to that in IRI-AKI rats treated with BMSC (29.7±0.8% versus 43.4±3.0%, P<0.05). In vitro, the cell proliferation rate of TSG-6-stimulated NRK-52E cells under hypoxia (89.2±3.9%) increased significantly compared to that of NRK-52E cells alone under hypoxia (82.4±0.8%, P<0.05). Similarly, the proportion of Ki67-positive cells was significantly elevated in TSG-6-stimulated NRK-52E cells under hypoxia. Furthermore, TSG-6 could inhibit infiltration of neutrophils in kidney tissue of IRI-AKI. Conclusions: TSG-6 plays a key role in the treatment of IRI-AKI with BMSC, which may be due to its effect on promoting renal tubular epithelial cells proliferation by modulating inflammation.


Assuntos
Lesão Renal Aguda/genética , Moléculas de Adesão Celular/genética , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/genética , Lesão Renal Aguda/patologia , Lesão Renal Aguda/terapia , Animais , Apoptose/genética , Células da Medula Óssea/citologia , Hipóxia Celular/genética , Linhagem Celular , Proliferação de Células/genética , Células Epiteliais/patologia , Humanos , Rim/lesões , Rim/metabolismo , Rim/patologia , Túbulos Renais/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Neutrófilos/patologia , Ratos , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia
13.
Dis Markers ; 2019: 5380197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944666

RESUMO

Cervical cancer is one of the most common malignant neoplasms in gynecology. Protein tyrosine kinase 7 (PTK7) with an inactive kinase domain is an important regulator of multiple Wnt pathways under normal and various pathological conditions and overexpressed in various tumors; however, the clinical and biological significance of PTK7 in cervical cancer is still unknown. In the present study, the protein expression level of PTK7 was detected in clinical cervical cancer patient samples, and the relationship between PTK7 expression and clinicopathological features was analyzed. In addition, the Kaplan-Meier method was performed to estimate the overall survival (OS) and progression-free survival (PFS) of patients to investigate the clinicopathological significance of PTK7 expression. Functional assays demonstrated that knocking down PTK7 might inhibit the ability of cancer cells to proliferate and invade or migrate, both in vivo and in vitro. Thus, PTK7 might serve as a potential target for cervical cancer.


Assuntos
Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/genética , Receptores Proteína Tirosina Quinases/genética , Neoplasias do Colo do Útero/genética , Animais , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Receptores Proteína Tirosina Quinases/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
14.
Cardiovasc Pathol ; 41: 11-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31004933

RESUMO

Atherosclerosis is a chronic inflammatory disease with lipid accumulation. Apolipoprotein C3 (APOC3), which is an important regulator of human lipid metabolism, is associated with multiple vascular mechanisms in atherosclerosis and proinflammatory responses. We have previously reported that the expression of inflammatory cytokine TNF-α is elevated in human endothelial cells (HUVECs) after APOC3 treatment. This study investigates the APOC3 signaling pathway involved in TNF-α-mediated expression of JAM-1 in HUVECs. Cultured HUVECs were exposed to APOC3 (50 µg/ml) for 16 h. Mechanistic studies were carried out by silencing TNF-α gene with lentiviral TNF-α-shRNA. Our study was based on the eight signaling pathway inhibitors to block the effect of APOC3 in HUVECs. The expression of JAM-1 was determined by qRT-PCR, Western blotting, and flow cytometry. IKK2 degradation and NF-κB p65 phosphorylation were determined by Western blotting. Our results showed that APOC3 significantly promoted the TNF-α-induced expression of JAM-1 in HUVECs. Inhibiting APOC3 reversed the TNF-α-induced overexpression of JAM-1. Moreover, APOC3 induced the expression of NF-κB p65 and degraded IκB. In conclusion, APOC3 promoted the expression of JAM-1 via the NF-κB, IKK2, and PI3K signaling pathway.


Assuntos
Apolipoproteína C-III/farmacologia , Moléculas de Adesão Celular/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Receptores de Superfície Celular/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Moléculas de Adesão Celular/genética , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Fosforilação , Proteólise , Interferência de RNA , Receptores de Superfície Celular/genética , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/enzimologia , Fator de Necrose Tumoral alfa/genética
15.
Int J Mol Sci ; 20(7)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30935090

RESUMO

BACKGROUND: In pregnancy, excessive inflammation and break down of immunologic tolerance can contribute to miscarriage. Endothelial cells (ECs) are able to orchestrate the inflammatory processes by secreting pro-inflammatory mediators and bactericidal factors by modulating leakiness and leukocyte trafficking, via the expression of adhesion molecules and chemokines. The aim of this study was to analyse the differences in the phenotype between microvascular ECs isolated from decidua (DECs) and ECs isolated from human skin (ADMECs). METHODS: DECs and ADMECs were characterized for their basal expression of angiogenic factors and adhesion molecules. A range of immunological responses was evaluated, such as vessel leakage, reactive oxygen species (ROS) production in response to TNF-α stimulation, adhesion molecules expression and leukocyte migration in response to TNF-α and IFN-γ stimulation. RESULTS: DECs produced higher levels of HGF, VEGF-A and IGFBP3 compared to ADMECs. DECs expressed adhesion molecules, ICAM-2 and ICAM-3, and a mild response to TNF-α was observed. Finally, DECs produced high levels of CXCL9/MIG and CXCL10/IP-10 in response to IFN-γ and selectively recruited Treg lymphocytes. CONCLUSION: DEC phenotype differs considerably from that of ADMECs, suggesting that DECs may play an active role in the control of immune response and angiogenesis at the foetal-maternal interface.


Assuntos
Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Pele/imunologia , Pele/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/genética , Quimiocina CXCL9/metabolismo , Decídua , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Imunofluorescência , Humanos , Técnicas In Vitro , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Molécula 3 de Adesão Intercelular/genética , Molécula 3 de Adesão Intercelular/metabolismo , Interferon gama/farmacologia , Neovascularização Patológica/metabolismo , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
16.
Indian J Pathol Microbiol ; 62(2): 206-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30971541

RESUMO

Context: Thyroid cancers are the most common malignancy of the endocrine system. Over-expression of trophoblast cell-surface antigen 2 (TROP-2) in various tumors has been found to correlate with poor prognosis and aggressive tumor behavior. Aims: The aim of this study was to evaluateTROP-2 expression in thyroid neoplasms. Subjects and Methods: This study contained 152 cases, including 48 follicular nodular disease (FND), 29 follicular adenoma (FA), 57 papillary thyroid carcinoma (PTC), 12 follicular thyroid carcinoma (FTC), 3 medullary thyroid carcinoma (MTC), 2 poorly differentiated thyroid carcinoma (PDTC) and 1 undifferentiated thyroid carcinoma (UDTC). TROP-2 expression was investigated via immunohistochemistry in sections prepared from paraffin blocks of the cases. Results: The cases comprised 32 (21%) males and 120 (79%) females with a mean age of 46.8 years (range, 15-85 years). TROP-2 expression was observed in 74.6% of the malignant lesions of the thyroid except for medullary carcinoma, poorly differentiated and undifferentiated thyroid carcinoma. Immunoreactivity was 3.4% in FA, 41.7% of cases with FTC and 81.8% in PTC follicular variant (PTC fv). The difference between FA/FTC and FA/PTC follicular variant were both significant (P < 0.005, P < 0.001, respectively). There was no difference between FTC/PTC fv (P = 0.089). Conclusion: TROP-2 can be considered a useful marker for distinguishing PTC fv cases from follicular nodular disease and follicular adenoma cases because of its high sensitivity in the identification of papillary carcinomas of the thyroid.


Assuntos
Adenocarcinoma Folicular/diagnóstico , Antígenos de Neoplasias/genética , Moléculas de Adesão Celular/genética , Câncer Papilífero da Tireoide/diagnóstico , Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnóstico , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-31027310

RESUMO

Objective: This study was conducted to identify the association between rs4804803 polymorphism in DC-SIGN with the susceptibility of severe dengue. Methods: A comprehensive search was conducted to identify all eligible papers in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Google Scholar. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to assess the association. Subgroup analyses were performed by ethnicity. Sensitivity analyses were performed through employing different statistical models (fixed versus random effect model). Results: A total of nine papers and 12 studies, with 1520 severe dengue and 1496 clinical dengue infection were included. The overall meta-analysis revealed significant associations between rs4804803 and severe dengue under the recession (GG versus GA/AA: OR = 0.44, 95%CI, 0.23-0.82) and a codominant model (GG versus AA: OR = 0.43, 95%CI, 0.23-0.81), but sensitivity analysis indicated that the significant pooled ORs were not robust. The subgroup analysis suggested that the carrier of G in rs4804803 was a risk factor for severe dengue under dominant (GG/GA versus AA: OR = 1.86,95%CI, 1.01-3.45), superdominant (GA versus GG/AA: OR = 1.81,95%CI, 1.02-3.21) and a codominant (GA versus AA: OR=1.82,95%CI, 1.02-3.26) models in Asians, while it was a protective factor for severe dengue in South-central Americans under recessive (GG versus GA/AA: OR = 0.27,95%CI, 0.10-0.70) and codominant (GG versus AA: OR=0.24,95%CI, 0.09-0.64) models. The results from subgroup analysis were robust. Conclusions: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) promoter-336G/A (rs4804803) polymorphism is association with severe dengue, and it acts in different directions for Asians and South-central Americans.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Moléculas de Adesão Celular/genética , Lectinas Tipo C/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Receptores de Superfície Celular/genética , Dengue Grave/genética , China , Predisposição Genética para Doença , Humanos , Razão de Chances , Fatores de Risco , Dengue Grave/etnologia , América do Sul
18.
J Agric Food Chem ; 67(18): 5240-5249, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31008594

RESUMO

Fluoride is a widespread environmental pollutant that can induce low sperm quality and fertilizing ability; however, the underlying mechanism still remains unclear. Hence, we aimed to investigate the influence of fluoride on the sperm fertilizing ability via some key proteins in the epididymis. For this, 40 adult rats were assigned randomly into four groups. The control group was given distilled water, while the other three groups were given 25, 50, and 100 mg of NaF/L via drinking water for 56 days, respectively. After 1 day, epididymides were processed for sperm-egg binding, RNA extraction, western blot, and immunofluorescence analysis. Fluoride exposure reduced the ability of sperm to break down the egg cumulus cell layer. A further study revealed that fluoride altered the expression levels of genes and proteins related to acrosome reaction in vivo, including SPAM1, ACR, and PRSS21. However, fluoride only affected the expression of the ACR protein only in the epididymis but not in the testis. Fluoride also affected the expression levels of the membrane proteins CD9 and CD81 of epididymosomes in the epididymis. From the results, it can be concluded that fluoride exposure reduced the ability of sperm to break down the egg cumulus cell layer, which could be one of the reasons for decreased fertility ability in males treated with fluoride. These results provide some theoretical guidance and new ideas for treatments of low fertility, infertility, and other reproductive diseases.


Assuntos
Acrosina/metabolismo , Moléculas de Adesão Celular/metabolismo , Epididimo/efeitos dos fármacos , Fluoretos/farmacologia , Hialuronoglucosaminidase/metabolismo , Serina Endopeptidases/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Acrosina/genética , Animais , Moléculas de Adesão Celular/genética , Epididimo/metabolismo , Fertilização/efeitos dos fármacos , Hialuronoglucosaminidase/genética , Masculino , Ratos , Ratos Sprague-Dawley , Serina Endopeptidases/genética , Testículo/efeitos dos fármacos , Testículo/metabolismo
19.
Ticks Tick Borne Dis ; 10(4): 729-741, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30879988

RESUMO

The human Tick-borne encephalitis virus (TBEV) infection is a complex event encompassing factors derived from the virus itself, the vectors, the final host, and the environment as well. Classically, genetic traits stand out among the human factors that modify the susceptibility and progression of infectious diseases. However, and although this is a changing scenario, studies evaluating the genetic factors that affect the susceptibility specifically to TBEV infection and TBEV-related diseases are still scarce. There are already some interesting pieces of evidence showing that some genes and polymorphisms have a real impact on TBEV infection. Also, the inflammatory processes involving tick-human interactions began to be understood in greater detail. This review focuses on the immunogenetic and inflammatory aspects concerning tick-host interactions, TBEV infections, and tick-borne encephalitis. Of note, it has been described that polymorphisms in CD209, GSTM1, IL-10, IL-28B, MMP9, OAS2, OAS3, and TLR3 have a statistically significant impact on TBEV infection. Besides, CCR5, its ligands, and the CCR5Δ32 genetic variant seem to have a very important influence on the infection and its immune responses. Taking this information into consideration, a special discussion regarding the effects of CCR5 on TBEV infection and tick-borne encephalitis will be presented. Emerging topics (such as exosomes, evasins, and CCR5 blockers) involving immunological and inflammatory aspects of TBEV-human interactions will also be addressed. Lastly, the current picture of TBEV infection and the importance to address the TBEV-associated problems through the One Health perspective will be discussed.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/imunologia , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Polimorfismo Genético , Receptores CCR5/genética , Animais , Moléculas de Adesão Celular/genética , Progressão da Doença , Suscetibilidade a Doenças/imunologia , Encefalite Transmitida por Carrapatos/genética , Humanos , Imunogenética , Interleucina-10/genética , Lectinas Tipo C/genética , Camundongos , Saúde Única , Receptores CCR5/imunologia , Receptores de Superfície Celular/genética
20.
Mol Cell Biochem ; 457(1-2): 83-91, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30825051

RESUMO

Epithelial-mesenchymal transition (EMT) leads to tumor dissemination and metastasis. Metadherin (MTDH) is an oncogene that plays an important role in metastasis regulation. This study tries to investigate the effect of MTDH gene up-regulation on the activation of EMT in colorectal cancer (CRC) cells and identify the role of NF-κB p65. The CaCO2 cells were divided into three groups: one control group of cultured CaCO2 cells (C1), and two groups of CaCO2 cells co-transfected using human MTDH expression plasmid with either siRNA targeting human NF-κB p65 or its negative control (C2 and C3 respectively). The gene modification was confirmed by qPCR and the effect of gene modification on CRC aggravation was studied. MTDH up-regulation significantly promoted CRC cell proliferation, activated anaerobic respiration (glucose consumption and lactate production), and increased gene expression of multidrug resistance gene (MDR1), Snail transcription factor and NF-κB p65, but decreased the gene expression of E-cadherin. Moreover, MTDH up-regulation led to a significant increase in the acquisition of surface markers of CRC stem cells. Interference with NF-κB p65 gene expression reversed the action of MTDH gene up-regulation on MDR1 and E-cadherin gene expression and anaerobic respiration. Moreover, NF-κB p65 interference significantly decreased MTDH-induced cell proliferation and acquisition of surface markers of CRC stem cells but didn't affect the Snail transcription factor. MTDH-dependent EMT in CRC is activated via NF-κB p65 and is mediated by up-regulation of Snail. These results identify a pathway by which MTDH regulates NF-κB p65 induced EMT during CRC cell metastasis.


Assuntos
Moléculas de Adesão Celular/biossíntese , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Fator de Transcrição RelA/biossíntese , Células CACO-2 , Moléculas de Adesão Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Metástase Neoplásica , Proteínas de Neoplasias/genética , Fator de Transcrição RelA/genética
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