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1.
Adv Exp Med Biol ; 1141: 467-504, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571172

RESUMO

Blood-retinal barrier (BRB) includes inner BRB (iBRB) and outer BRB (oBRB), which are formed by retinal capillary endothelial (RCEC) cells and by retinal pigment epithelial (RPE) cells in collaboration with Bruch's membrane and the choriocapillaris, respectively. Functions of the BRB are to regulate fluids and molecular movement between the ocular vascular beds and retinal tissues and to prevent leakage of macromolecules and other potentially harmful agents into the retina, keeping the microenvironment of the retina and retinal neurons. These functions are mainly attributed to absent fenestrations of RCECs, tight junctions, expression of a great diversity of transporters, and coverage of pericytes and glial cells. BRB existence also becomes a reason that systemic administration for some drugs is not suitable for the treatment of retinal diseases. Some diseases (such as diabetes and ischemia-reperfusion) impair BRB function via altering tight junctions, RCEC death, and transporter expression. This chapter will illustrate function of BRB, expressions and functions of these transporters, and their clinical significances.


Assuntos
Barreira Hematorretiniana , Proteínas de Membrana Transportadoras , Expressão Gênica , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Retina/metabolismo , Doenças Retinianas/fisiopatologia , Junções Íntimas
2.
Anticancer Res ; 39(10): 5715-5720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570472

RESUMO

BACKGROUND/AIM: The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS: PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS: Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION: PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.


Assuntos
Expressão Gênica/genética , Isoenzimas/genética , Proteína Quinase C/genética , Neoplasias Gástricas/genética , Gastrectomia/métodos , Mucosa Gástrica/patologia , Humanos , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/patologia
3.
Medicine (Baltimore) ; 98(39): e17311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574860

RESUMO

Immune infiltration of nasopharyngeal carcinoma (NPC) is closely associated with the patients' prognosis. However, previous studies have not interpreted the difference of infiltrating immune cells in NPC.We comprehensively analyzed the tumor-infiltrating immune cells present in NPC for the first time, which was based on a scientific deconvolution algorithm (CIBERSORT) and the gene expression data of GSE64634. The fractions of 22 immune cells were assessed to reveal the associations between normal samples and NPC samples.Profiles of immune infiltration vary significantly between normal samples and NPC samples, and the variation could characterize the individual differences. NPC samples contained a higher proportion for M1 macrophages, whereas memory B cells and CD4 memory resting T cells were relatively lower.Our data suggest that the differences in the infiltrating immune cells in NPC and these differences would probably facilitate patient consultation and individualized treatment.


Assuntos
Linfócitos do Interstício Tumoral , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adulto , Algoritmos , Linfócitos B/imunologia , Linfócitos B/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , China , Correlação de Dados , Feminino , Expressão Gênica , Humanos , Memória Imunológica , Linfócitos do Interstício Tumoral/classificação , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Prognóstico , Reprodutibilidade dos Testes
4.
Arq. bras. cardiol ; 113(2 supl.1): 106-106, set., 2019.
Artigo em Português | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1017311

RESUMO

INTRODUÇÃO: O processo de senescência do coração e de suas valvas vem sendo correlacionado com a ação do subtipo 1 de endotelina (ET-1) e de seus receptores (ETrA e ETrB). A produção de ET-1 é dependente de cálcio extracelular; estando associada à resposta inflamatória encontrada no envelhecimento, quando ocorre substituição fibrosa e calcificação nas valvas mitral e aórtica. OBJETIVO: Avaliar se há expressão gênica da endotelina-1 no processo de envelhecimento valvar. RESULTADOS: As concentrações médias de ácido nucléico (RNA total) e de cDNA foram respectivamente de 27,21±30,26 ng/ul e de 609,4±80,60ng/ul. Os valores médios de absorbância em 260 e 280nm foram respectivamente de 0,67±0,74 UA (A260) e de 0,33±0,36 UA (A280). Já a proporção A260/A280 foi de 1,91±0,20. Das sete amostras coletadas, observou-se a expressão de ET-1 em todas elas, sendo que, quantitativamente, a expressão gênica média relativa para ET-1 foi de 62,85±25,63%. CONCLUSÃO: A ET-1 está relacionada à vasoconstricção e a processos inflamatórios presentes na senescência valvar, portanto, sua expressão já era esperada, confirmando-se assim, o seu envolvimento na homeostase cardiovascular. (AU)


Assuntos
Humanos , Idoso de 80 Anos ou mais , Expressão Gênica , Endotelinas
5.
J Agric Food Chem ; 67(38): 10595-10603, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31475817

RESUMO

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , beta-Criptoxantina/administração & dosagem , Obesidade/tratamento farmacológico , Receptores do Ácido Retinoico/metabolismo , Proteína Desacopladora 1/genética , Animais , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Receptores do Ácido Retinoico/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
6.
Ann Agric Environ Med ; 26(3): 392-395, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31559791

RESUMO

Existing research for using the protective antigen (PA) of Bacillus anthracis as a vaccine component shows that protection against anthrax may be obtained using fragments of this protein. The aim of the research is to check whether the selected protein fragment of the protective antigen (domain 4) encoded by an appropriate nucleotide sequence of gene pag of B. anthracis, was expressed in the bacterial system of E. coli. In order to examine the selected sequence of the pag gene, a PCR reaction and a highly effective TOPO cloning strategy were used, followed by purification of the recombinant proteins and their detection by a western-blot method. In the planning of the PA4 antigen expression a higher level of effectiveness in production of small protein - domain 4 - was anticipated. As a result, the 139 amino acids protein fragment of B. anthracis PA (domain 4) was isolated. The research may have found the basis for in vivo research aimed at finding potential anthrax vaccine components.


Assuntos
Vacinas contra Antraz/imunologia , Antraz/microbiologia , Antígenos de Bactérias/imunologia , Bacillus anthracis/imunologia , Toxinas Bacterianas/imunologia , Animais , Antraz/imunologia , Antraz/prevenção & controle , Vacinas contra Antraz/administração & dosagem , Vacinas contra Antraz/genética , Vacinas contra Antraz/isolamento & purificação , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/imunologia , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/genética , Antígenos de Bactérias/isolamento & purificação , Bacillus anthracis/química , Bacillus anthracis/genética , Toxinas Bacterianas/administração & dosagem , Toxinas Bacterianas/genética , Toxinas Bacterianas/isolamento & purificação , Western Blotting , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Domínios Proteicos
7.
Zhonghua Yi Xue Za Zhi ; 99(35): 2745-2749, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550796

RESUMO

Objective: To investigatea cellular/molecular mechanism of the CD40/TRAF1 signalling pathway involved in Rheumatoid arthritis (RA). Methods: 16 patients with active RA and 9 patients with Fractures who underwent total knee or hip replacement in The First Affiliated Hospital of Soochow University were included in the study. Synovial tissues (ST) and serum were obtained from each patient. The CD40, TRAF1, NF-κB p65 were detected by ELISA and Immunohistochemistry in serum and tissue respectively. Real time-PCR (RT-PCR) was applied to measure NF-κB-related gene expression. Results: CD40 and TRAF1 positive area (%) in RA patients were 28.7±5.4, 34.3±4.8 respectively, which were significantly higher (P<0.05) than Fracture controls (21.2±9.5, 21.6±8.7 respectively). The expression of total NF-κB p65, and phospho-NF-κB p65 proteins, as well as NF-κB-related gene expression, including cytokines (TNFα, IL-6), chemokines (MCP-1),and adhesion molecules (ICAM-1) were significantly higher in the ST of RA patients compared to Fracture controls. Conclusion: It is thus possible that the CD40/TRAF1 pathway acted as a positive regulator through NF-κB activation and NF-κB-dependent proinflammatory genes in RA.


Assuntos
Artrite Reumatoide/genética , Antígenos CD40/metabolismo , Transdução de Sinais , Fator 1 Associado a Receptor de TNF/metabolismo , Fator de Transcrição RelA/metabolismo , Antígenos CD40/genética , Células Cultivadas , Expressão Gênica , Humanos , Membrana Sinovial , Fator 1 Associado a Receptor de TNF/genética , Fator de Transcrição RelA/genética
8.
Acta Virol ; 63(3): 322-327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507199

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which are rare in western countries but with high incidence in Southern Asia especially South China. NPC is relatively sensitive to radiotherapy, but the prognosis of patients in late stage is poor. The development of NPC is closely related to genetic background, Epstein-Barr virus (EBV) infection and life style. EBV latent membrane protein 1 (LMP1) is an oncoprotein, which plays important roles in the tumorigenesis of NPC. LMP1 was reported to be involved in the regulation of cancer stem cells (CSCs) by immunohistochemistry (IHC) and other surface marker staining methods, but not shown by aldehyde dehydrogenase 1 (ALDH-1) functional assay yet. In this study, we overexpressed LMP1 in two NPC cell lines and found elevated level of cytokeratin 19 (CK19) expression. CK19 is an undifferentiated keratin and a stem cell marker. We also have found an increased number of ALDH positive cells along with LMP1 overexpression in both cell lines. Our data demonstrate that LMP1 regulates the maintenance of ALDH-1 positive NPC cancer stem cells, thus shedding light on target therapy of NPC in clinical application. Keywords: nasopharyngeal carcinoma; latent membrane protein 1; aldehyde dehydrogenase; cancer stem cells.


Assuntos
Aldeído Desidrogenase , Infecções por Vírus Epstein-Barr , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Proteínas da Matriz Viral , Aldeído Desidrogenase/metabolismo , Linhagem Celular Tumoral , China , Infecções por Vírus Epstein-Barr/fisiopatologia , Expressão Gênica , Humanos , Queratina-19/genética , Carcinoma Nasofaríngeo/fisiopatologia , Neoplasias Nasofaríngeas/fisiopatologia , Proteínas da Matriz Viral/metabolismo
10.
Anticancer Res ; 39(9): 4637-4642, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519561

RESUMO

AIM: The aim of this study was to characterize the role of Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis chromosomal region gene 1 (AMMECR1) in human lung cancer cell lines. MATERIALS AND METHODS: AMMECR1 gene expression was evaluated in four lung cell lines, with A549 then selected for further in-depth examination. To characterize the role of AMMECR1, silencing was achieved utilizing lentivirus-mediated RNA interference, and confirmed by quantitative real-time polymerase chain reaction and western blotting. The impact of AMMECR1 silencing on cellular proliferation was assessed using Celigo-based and MTT assays. Apoptosis was determined using the annexin V-allophycocyanin single staining method. Cell-cycle arrest was assessed by flow cytometry. Finally, colony formation was assessed using Giemsa staining. RESULTS: In A549 cells, AMMECR1 silencing was found to significantly suppress cell proliferation, reduce colony formation, promote apoptosis, and arrest cells in the S and G2/M phases. CONCLUSION: AMMECR1 plays a critical role in cell proliferation, cell-cycle progression, and apoptosis of human lung cancer cells, and may serve as a potential therapeutic target for non-small-cell lung cancer.


Assuntos
Apoptose/genética , Ciclo Celular/genética , Neoplasias Pulmonares/genética , Proteínas/genética , Células A549 , Linhagem Celular Tumoral , Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas/metabolismo , RNA Mensageiro/genética
11.
Anticancer Res ; 39(9): 4673-4679, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519566

RESUMO

BACKGROUND/AIM: Rats of the adenomatous polyposis coli (Apc)-mutated female polyposis in rat (PIRC) (F344/NTac-Apcam1137) model exhibit a low level of intestinal tumorigenesis and are thus potentially exploitable as a model for identifying substances increasing colorectal cancer (CRC). MATERIALS AND METHODS: To test this possibility, we treated such rats with the bile acid (BA) cholic acid (CA) (0.3% w/w in the diet), known to promote CRC, and assessed tumorigenesis. RESULTS: Precancerous colonic lesions (mucin-depleted foci) and intestinal tumors were dramatically increased in CA-treated rats compared to controls (p<0.01). Colon mucosa proliferation was higher and apoptosis lower than those in controls. Expression of nuclear receptor 1h4 (Nr1h4) gene [encoding for BA receptor farnesoid X receptor (FXR)], organic solute transporter beta (Ostb) and fatty acid-binding protein 6 (Fabp6), FXR-dependent BA transporters, were dramatically down-regulated in CA-treated rats. CONCLUSION: CA-increased tumorigenesis in female PIRC rats, with mechanisms involving increased proliferation, reduced apoptosis and marked down-regulation of genes controlling BA homeostasis. Since BAs have been implicated in CRC, we suggest that female PIRC rats can be used to identify CRC-promoting agents.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Ácido Cólico/efeitos adversos , Neoplasias Colorretais/etiologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Animais , Apoptose/genética , Proliferação de Células , Modelos Animais de Doenças , Feminino , Expressão Gênica , Genes APC , Mutação , Lesões Pré-Cancerosas , Ratos
12.
Anticancer Res ; 39(9): 4681-4685, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519567

RESUMO

BACKGROUND/AIM: S100A8 is a chemoattractant known to be associated with metastatic niche formation. Herein, we evaluated the prognostic value of S100A8 in patients with clear cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: A total of 152 CCRCC patients who have undergone nephrectomy were enrolled. The expression of S100A8 was assessed immunohistochemically using tissue microarray (TMA) blocks of CCRCC. Using statistical analysis, the relationship between S100A8 expression and clinicopathological factors was evaluated. RESULTS: Among 152 TMA cores, 21 (6.9%) showed higher S100A8 expression. S100A8 expression was significantly increased in cores of patients with higher T stage (≥2, p<0.001) and higher Fuhrman nuclear grade (≥3, p<0.001). Multivariate analysis confirmed that high expression of S100A8 was significantly correlated to poor disease-free survival (hazard ratio, 2.601; 95% confidence interval (CI), 1.020-6.628; p-value=0.045). CONCLUSION: S100A8 expression may have a prognostic value in CCRCC reflecting TNM staging and Fuhrman nuclear grade.


Assuntos
Biomarcadores Tumorais , Calgranulina A/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Calgranulina A/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
13.
Anticancer Res ; 39(9): 4737-4742, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519573

RESUMO

BACKGROUND/AIM: There are several unresolved issues regarding the combined treatment with an immune checkpoint inhibitor and anti-angiogenic agent for renal cell carcinoma (RCC) patients. The purpose of this study was to address the inhibitory effects of programmed death-ligand 1 (PD-L1) expression on growth and sensitivity to sunitinib in the mouse RCC RenCa model. MATERIALS AND METHODS: We established RenCa/sh-PD-L1 by transfecting RenCa cells with a plasmid carrying a short hairpin RNA targeted against PD-L1. The growth pattern of RenCa/sh-PD-L1 with or without sunitinib was compared to that of RenCa cells transfected with control plasmid alone (RenCa/Co). RESULTS: No significant difference in growth or sensitivity to sinitinib was noted between RenCa/sh-PD-L1 and RenCa/Co cells in vitro. The tumor volume in mice subcutaneously injected with RenCa/sh-PD-L1 was significantly smaller than that with RenCa/Co. Treatment of mice bearing each tumor with sunitinib resulted in a significant reduction of the RenCa/sh-PD-L1 tumor compared to the RenCa/Co tumor. Moreover, infiltration by CD8+ T cells of RenCa/sh-PD-L1 tumors was significantly higher than that of RenCa/Co tumors, irrespective of treatment with sunitinib. CONCLUSION: Suppressed expression of PD-L1 could increase tumor-infiltrating CD8+ T cells and result in growth inhibition as well as enhanced sensitivity to sunitinib in the RenCa model.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , RNA Interferente Pequeno/genética , Sunitinibe/farmacologia , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Expressão Gênica , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Camundongos , Carga Tumoral/efeitos dos fármacos
14.
Anticancer Res ; 39(9): 4811-4816, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519583

RESUMO

BACKGROUND/AIM: γ-Glutamylcyclotransferase (GGCT) is highly expressed in many forms of cancer, and is a promising therapeutic target. The present study investigated whether inhibition of GGCT enhanced the antiproliferative effects of the drug docetaxel in prostate cancer cells. MATERIALS AND METHODS: Immunohistochemistry and western blot analysis were conducted to measure GGCT expression in prostate cancer tissue samples and cell lines. GGCT was inhibited using RNAi and a novel enzymatic inhibitor, pro-GA, and cell proliferation was evaluated with single and combination treatments of GGCT inhibitors and docetaxel. RESULTS: GGCT was highly expressed in cultured prostate cancer cells and patient samples. GGCT inhibition alone inhibited prostate cancer cell line proliferation and induced cellular senescence. GGCT inhibition in combination with apoptosis-inducing docetaxel had more potent antiproliferative effects than either drug used alone. CONCLUSION: GGCT inhibition may potentiate anticancer drug efficacy.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Inibidores Enzimáticos/farmacologia , gama-Glutamilciclotransferase/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/genética , gama-Glutamilciclotransferase/genética , gama-Glutamilciclotransferase/metabolismo
15.
Medicine (Baltimore) ; 98(37): e17143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517857

RESUMO

The aim of this study was to investigate the alterations of urinary microRNA (miRNA) expression and explore its clinical significance in patients with chronic hepatitis B (CHB).The expression levels of urinary miRNA were detected by miRNA microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) from 106 CHB and 40 healthy controls (Ctrl) subjects. The correlation between the levels of miRNA expression and clinical characteristics were analyzed. Receiver-operator characteristic (ROC) curves were generated to determine the specificity and sensitivity of each individual miRNA. MiRNAs expression were further measured by PCR from exosomes, which were isolated from urine samples. LX2 cells were transfected with miRNA inhibitor and accumulation of cytoplasmic lipid droplets was analyzed by Oil Red O staining.miRNA expression profile analysis showed that 22 miRNAs were upregulated and 55 miRNAs were downregulated in CHB patients compared with Ctrl subjects (fold-change>1.5 and P < .05). miR-92b-3p, miR-770-5p, miR-5196-5p, and miR-7855-5p were significantly higher (P < .0001) in CHB subjects than in Ctrl subjects. ROC curve analysis showed that these four miRNAs were sensitive and specific enough to distinguish CHB and Ctrl subjects. The levels of miR-92b-3p expression were negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and APOA-1. Moreover, in vitro experiments indicated that inhibition of miR-92b-3p increased lipid droplet formation in LX2 cells.Aberrant expression of miRNAs has been observed in urine of CHB patients. Our findings may provide novel insights into the pathogenesis of CHB and may assist in the diagnosis of patients with CHB.


Assuntos
Hepatite B Crônica/urina , MicroRNAs/urina , Adulto , Biomarcadores/urina , Linhagem Celular , Exossomos/metabolismo , Feminino , Expressão Gênica , Humanos , Gotículas Lipídicas/metabolismo , Masculino , Sensibilidade e Especificidade
16.
Medicine (Baltimore) ; 98(37): e17156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517861

RESUMO

This study aims to screen differentially expressed host miRNAs that could be used as diagnostic markers for liver alveolar echinococcosis (LAE).Differentially expressed miRNAs were first screened by miRNA microarray in liver tissues from2 LAE patients and normal liver tissues from 3 LAE patients, followed by qRT-PCR validation in 15 LAE tissues and 15 normal tissues. Target genes of differentially expressed miRNAs were predicted using Targetscan, PITA and microRNAorg database, and the overlapped predicted target genes were analyzed by GO and KEGG.The hsa-miR-1237-3p, hsa-miR-33b-3p, and hsa-miR-483-3p were up-regulated whereas the hsa-miR-4306 was down-regulated in LAE tissues compared with normal controls (P < .05). The expression change of miR-483-3p was further confirmed in both liver tissues and plasma. Several predicted targets of miR-1237-3p, miR-4306, and miR-483-3p were related to DNA-dependent transcriptional regulation, developmental regulation of multicellular organisms, and biological functions such as cellular immune responses (T cell proliferation). The overlapped predicted target genes of the 4 differentially expressed miRNAs were enriched in mRNA surveillance, cancer signaling pathway, intestinal immune network, and other signal pathways.Our results indicate that miR-483-3p is a potential marker for the diagnosis of LAE, and targets of this miRNA could be the focus of further studies.


Assuntos
Equinococose Hepática/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade
17.
Medicine (Baltimore) ; 98(33): e16711, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415363

RESUMO

BACKGROUND: Multiple myeloma (MM) is a clonal plasma cell malignancy associated with hypercalcemia, bone lesions, and renal failure. The prognostic significance of the mutation of miRNAs, one kind of small noncoding RNA molecules that can modulate gene expression, should be confirmed in non-Hodgkin lymphomas (NHL). This study aimed to identify the prognostic value of miRNAs in patients with MM. METHODS: A meta-analysis was performed to estimate the pooled hazard ratios and their corresponding 95% confidence intervals for the associations between levels of miRNA expression (predictive factors) and outcomes in patients with MM. We systematically searched the PubMed, Web of Science, and China National Knowledge Infrastructure databases (final search conducted January 1, 2018) to identify eligible studies. Eligible studies were included by certain inclusion and exclusion criteria, whose quality was assessed by Newcastle-Ottawa Scale. RESULTS: After performing the literature search and review, 10 relevant studies, including 1214 cases, were identified. The results of our meta-analysis revealed that upregulated miR-92a level and downregulated miR-16, miR-25, miR-744, miR-15a, let-7e, and miR-19b expression were associated with poor prognosis in MM. CONCLUSIONS: This study identified miRNAs could serve as potential prognostic biomarkers in MM. Given the limited research available, the clinical application of these findings has yet to be verified.


Assuntos
MicroRNAs/metabolismo , Mieloma Múltiplo/genética , Biomarcadores Tumorais/metabolismo , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Masculino , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Regulação para Cima
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1026-1032, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418352

RESUMO

OBJECTIVE: To investigate the expression of erythropoietin (EPO) and erythropoietin receptor (EPOR) in patients with acute leukemia (AL) and its clinical significance. METHODS: The levels of EPO and EPOR in plasma were determined by ELISA kit. mRNA expression levels of EPO and EPOR were determined by RT-RCR. The protein expression levels of EPO and EPOR were detected by Western blot. RESULTS: The EPO protein levels in marrow plasma of ALL and AML group were significantly higher than those in the control group (P<0.05), EPOR protein levels in ALL and AML group were significantly lower than those in the control group (P<0.05). The mRNA levels of EPO and EPOR in ALL and AML groups were significantly higher than those in the control group (P<0.05). The mRNA levels of EPO and EPOR in the high risk ALL and AML groups were significantly higher than those in the medium, low risk group and the control group (P<0.05). The protein expression levels of EPO and EPOR in ALL and AML groups were significantly higher than that in control group (P<0.05). The mRNA levels of EPO and EPOR in ALL and AML groups did not correlate with hemoglobin level and erythrocyte count (P>0.05). CONCLUSION: The expressions of EPO and EPOR is higher in ALL and AML patients. The expression levels of EPO and EPOR relate with the risk of ALL and AML. High risk patients have higher expression levels of EPO and EPOR, however, the expression levels of EPO and EPOR do not correlate with hemoglobin level and erythrocyte counting.


Assuntos
Leucemia Mieloide Aguda , Medula Óssea , Eritropoetina , Expressão Gênica , Humanos , Receptores da Eritropoetina
19.
BMC Plant Biol ; 19(1): 372, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438864

RESUMO

BACKGROUND: Correct timing of flowering is critical for plants to produce enough viable offspring. In Arabidopsis thaliana (Arabidopsis), flowering time is regulated by an intricate network of molecular signaling pathways. Arabidopsis srr1-1 mutants lacking SENSITIVITY TO RED LIGHT REDUCED 1 (SRR1) expression flower early, particularly under short day (SD) conditions (1). SRR1 ensures that plants do not flower prematurely in such non-inductive conditions by controlling repression of the key florigen FT. Here, we have examined the role of SRR1 in the closely related crop species Brassica napus. RESULTS: Arabidopsis SRR1 has five homologs in Brassica napus. They can be divided into two groups, where the A02 and C02 copies show high similarity to AtSRR1 on the protein level. The other group, including the A03, A10 and C09 copies all carry a larger deletion in the amino acid sequence. Three of the homologs are expressed at detectable levels: A02, C02 and C09. Notably, the gene copies show a differential expression pattern between spring and winter type accessions of B. napus. When the three expressed gene copies were introduced into the srr1-1 background, only A02 and C02 were able to complement the srr1-1 early flowering phenotype, while C09 could not. Transcriptional analysis of known SRR1 targets in Bna.SRR1-transformed lines showed that CYCLING DOF FACTOR 1 (CDF1) expression is key for flowering time control via SRR1. CONCLUSIONS: We observed subfunctionalization of the B. napus SRR1 gene copies, with differential expression between early and late flowering accessions of some Bna.SRR1 copies. This suggests involvement of Bna.SRR1 in regulation of seasonal flowering in B. napus. The C09 gene copy was unable to complement srr1-1 plants, but is highly expressed in B. napus, suggesting specialization of a particular function. Furthermore, the C09 protein carries a deletion which may pinpoint a key region of the SRR1 protein potentially important for its molecular function. This is important evidence of functional domain annotation in the highly conserved but unique SRR1 amino acid sequence.


Assuntos
Brassica napus/genética , Flores/genética , Genes de Plantas , Proteínas de Plantas/genética , Flores/crescimento & desenvolvimento , Dosagem de Genes , Expressão Gênica , Filogenia , Proteínas de Plantas/fisiologia
20.
World J Microbiol Biotechnol ; 35(8): 127, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375931

RESUMO

Aeromonas hydrophila is a Gram-negative bacterium that causes serious infections in aquaculture and exhibits significant multidrug resistance. The LysR-type transcriptional regulator (LTTR) family proteins are a well-known group of transcriptional regulators involved in diverse physiological functions. However, the role of LTTRs in the regulation of bacterial resistance to antibiotics is still largely unknown. In this study, to further investigate the role of four putative LTTR family proteins (A0KIU1, A0KJ82, A0KPK0, and A0KQ63) in antibiotic resistance in A. hydrophila, their genes were cloned and overexpressed in engineered Escherichia coli. After the optimization of experimental conditions including incubation time, temperature, and IPTG concentration, these proteins were successfully purified, and their specific antibodies against mice were obtained. Using western blot analysis, we found that these LTTR family proteins were downregulated in A. hydrophila following antibiotic treatment, indicating that they may be involved in the regulation of antibiotic resistance. Additionally, minimum inhibitory concentration (MIC) assays of chloramphenicol (CM), chlortetracycline (CTC), ciprofloxacin (CF), furazolidone (FZ), and balofloxacin (BF) in E. coli showed that overexpression of these LTTRs led to increased sensitivity to several antibiotics. To further validate their functional role in antibiotic resistance, we demonstrated that bacteria with loss of A0KQ63 (ΔAHA_3980) exhibited multi-drug resistance properties. Our results indicate that these LTTR family proteins may play an important role in the antibiotic resistance of A. hydrophila, and the that underlying mechanisms controlling antibiotic resistance should be further investigated.


Assuntos
Aeromonas hydrophila/efeitos dos fármacos , Aeromonas hydrophila/genética , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Fatores de Transcrição/metabolismo , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Western Blotting , Clonagem Molecular , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Deleção de Genes , Expressão Gênica , Perfilação da Expressão Gênica , Genes Bacterianos , Camundongos , Testes de Sensibilidade Microbiana , Fatores de Transcrição/análise , Fatores de Transcrição/genética
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