Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Arterioscler Thromb Vasc Biol ; 41(12): 2961-2973, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34670409

RESUMO

OBJECTIVE: Vascular smooth muscle cell (SMC) proliferation contributes to neointima formation following vascular injury. Circular RNA-a novel type of noncoding RNA with closed-loop structure-exhibits cell- and tissue-specific expression patterns. However, the role of circular RNA in SMC proliferation and neointima formation is largely unknown. The objective of this study is to investigate the role and mechanism of circSOD2 in SMC proliferation and neointima formation. Approach and Results: Circular RNA profiling of human aortic SMCs revealed that PDGF (platelet-derived growth factor)-BB up- and downregulated numerous circular RNAs. Among them, circSOD2, derived from back-splicing event of SOD2 (superoxide dismutase 2), was significantly enriched. Knockdown of circSOD2 by short hairpin RNA blocked PDGF-BB-induced SMC proliferation. Inversely, circSOD2 ectopic expression promoted SMC proliferation. Mechanistically, circSOD2 acted as a sponge for miR-206, leading to upregulation of NOTCH3 (notch receptor 3) and NOTCH3 signaling, which regulates cyclin D1 and CDK (cyclin-dependent kinase) 4/6. In vivo studies showed that circSOD2 was induced in neointima SMCs in balloon-injured rat carotid arteries. Importantly, knockdown of circSOD2 attenuated injury-induced neointima formation along with decreased neointimal SMC proliferation. CONCLUSIONS: CircSOD2 is a novel regulator mediating SMC proliferation and neointima formation following vascular injury. Therefore, circSOD2 could be a potential therapeutic target for inhibiting the development of proliferative vascular diseases.

2.
Pharmacol Ther ; : 107991, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592203

RESUMO

In eukaryotes, precursor mRNAs (pre-mRNAs) produce a unique class of biologically active molecules namely circular RNAs (circRNAs) with a covalently closed-loop structure via back-splicing. Because of this unconventional circular form, circRNAs exhibit much higher stability than linear RNAs due to the resistance to exonuclease degradation and thereby play exclusive cellular regulatory roles. Recent studies have shown that circRNAs are widely expressed in eukaryotes and display tissue- and disease-specific expression patterns, including in the cardiovascular system. Although numerous circRNAs are discovered by in silico methods, a limited number of circRNAs have been studied. This review intends to summarize the current understanding of the characteristics, biogenesis, and functions of circRNAs and delineate the practical approaches for circRNAs investigation. Moreover, we discuss the emerging roles of circRNAs in cardiovascular diseases.

3.
Int J Gynaecol Obstet ; 153(1): 154-159, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33098114

RESUMO

OBJECTIVE: To examine whether group prenatal care (PNC) increased key services and educational topics women reported receiving, compared with individual PNC in Malawi and Tanzania. METHODS: Data come from a previously published randomized trial (n=218) and were collected using self-report surveys. Late pregnancy surveys asked whether women received all seven services and all 13 topics during PNC. Controlling for sociodemographics, country, and PNC attendance, multivariate logistic regression used forward selection to produce a final model showing predictors of receipt of all key services and topics. RESULTS: In multivariate logistic regression, women in group PNC were 2.49 times more likely to receive all seven services than those in individual care (95% confidence interval [CI] 1.78-3.48) and 5.25 times more likely to have received all 13 topics (95% CI 2.62-10.52). CONCLUSION: This study provides strong evidence that group PNC meets the clinical standard of care for providing basic clinical services and perinatal education for pregnant women in sub-Saharan Africa. The greater number of basic PNC services and educational topics may provide one explanatory mechanism for how group PNC achieves its impact on maternal and neonatal outcomes. ClinicalTrials.gov: NCT03673709, NCT02999334.


Assuntos
Cuidado Pré-Natal/métodos , Educação Pré-Natal/métodos , Adulto , Feminino , Humanos , Modelos Logísticos , Malaui , Projetos Piloto , Gravidez , Gestantes , Tanzânia , Adulto Jovem
4.
Am J Physiol Cell Physiol ; 319(1): C105-C115, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32374674

RESUMO

Transforming growth factor-ß (TGF-ß)-induced fibroblast activation is a key pathological event during tissue fibrosis. Long noncoding RNA (lncRNA) is a class of versatile gene regulators participating in various cellular and molecular processes. However, the function of lncRNA in fibroblast activation is still poorly understood. In this study, we identified growth arrest-specific transcript 5 (GAS5) as a novel regulator for TGF-ß-induced fibroblast activation. GAS5 expression was downregulated in cultured fibroblasts by TGF-ß and in resident fibroblasts from bleomycin-treated skin tissues. Overexpression of GAS5 suppressed TGF-ß-induced fibroblast to myofibroblast differentiation. Mechanistically, GAS5 directly bound mothers against decapentaplegic homolog 3 (Smad3) and promoted Smad3 binding to Protein phosphatase 1A (PPM1A), a Smad3 dephosphatase, and thus accelerated Smad3 dephosphorylation in TGF-ß-treated fibroblasts. In addition, GAS5 inhibited fibroblast proliferation. Importantly, local delivery of GAS5 via adenoviral vector suppressed bleomycin-induced skin fibrosis in mice. Collectively, our data revealed that GAS5 suppresses fibroblast activation and fibrogenesis through inhibiting TGF-ß/Smad3 signaling, which provides a rationale for an lncRNA-based therapy to treat fibrotic diseases.


Assuntos
Fibroblastos/metabolismo , RNA Longo não Codificante/biossíntese , Transdução de Sinais/fisiologia , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Animais , Fibroblastos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , RNA Longo não Codificante/genética , Dermatopatias/genética , Dermatopatias/patologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismo
6.
Biochim Biophys Acta Mol Basis Dis ; 1865(9): 2516-2525, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31167125

RESUMO

Vascular remodeling is a pathological process following cardiovascular intervention. Vascular smooth muscle cells (VSMC) play a critical role in the vascular remodeling. Long noncoding RNAs (lncRNA) are a class of gene regulators functioning through various mechanisms in physiological and pathological conditions. By using cultured VSMC and rat carotid artery balloon injury model, we found that lncRNA growth arrest specific 5 (GAS5) serves as a negative regulator for VSMC survival in vascular remodeling. By manipulating GAS5 expression via adenoviral overexpression or short hairpin RNA knockdown, we found that GAS5 suppresses VSMC proliferation while promoting cell cycle arrest and inducing cell apoptosis. Mechanistically, GAS5 directly binds to p53 and p300, stabilizes p53-p300 interaction, and thus regulates VSMC cell survival via induction of p53-downstream target genes. Importantly, local delivery of GAS5 via adenoviral vector suppresses balloon injury-induced neointima formation along with an increased expression of p53 and apoptosis in neointimal SMCs. Our study demonstrated for the first time that GAS5 negatively impacts VSMC survival via activation the p53 pathway during vascular remodeling.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Lesões das Artérias Carótidas/complicações , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/veterinária , Proliferação de Células , Células Cultivadas , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Neointima/etiologia , Neointima/patologia , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Ubiquitinação
7.
Int J Offender Ther Comp Criminol ; 63(11): 1990-2017, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30938214

RESUMO

Drug courts aim to significantly address drug abuse and drug-related criminality. However, the effectiveness of drug courts varies from court to court. The variation of success demands insights regarding what is going on inside the "black box" of drug court practices. Therefore, it is necessary to evaluate to what extent drug courts are operated in adherence with guiding principles and strategies. Using a national sample and validated measures, the current article examines the "black boxes" of adult and juvenile drug courts across the country. We found that, in general, adult drug courts face less model adherence challenges in comparison with juvenile courts, which may, in part, explain why adult drug courts perform better than juvenile drug courts overall.


Assuntos
Tráfico de Drogas/legislação & jurisprudência , Comunicação Interdisciplinar , Colaboração Intersetorial , Adolescente , Adulto , Fatores Etários , Humanos , Modelos Teóricos , Estados Unidos
8.
FASEB J ; 32(9): 4836-4847, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29579398

RESUMO

Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32-/-) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be determined. In the present study, RGC-32 expression in white adipose tissue (WAT) was suppressed during cold exposure-induced WAT browning. Rgc32-/- significantly increased thermogenic gene expression in the differentiated stromal vascular fraction (SVF) of inguinal (i)WAT and interscapular brown adipose tissue (BAT). Rgc32-/- and cold exposure regulated a common set of genes in iWAT, as shown by RNA sequencing data. Pathway enrichment analyses showed that Rgc32-/- down-regulated PI3K/Akt signaling-related genes. Akt phosphorylation was also consistently decreased in Rgc32-/- iWAT, which led to an increase in ß3-adrenergic receptor (ß3-AR) expression and subsequent activation of mammalian target of rapamycin complex (mTORC)-1. ß3-AR antagonist SR 59230A and mTORC1 inhibitor rapamycin blocked Rgc32-/--induced thermogenic gene expression in both iWAT and interscapular BAT. These results indicate that RGC-32 suppresses adipose tissue thermogenic gene expression through down-regulation of ß3-AR expression and mTORC1 activity via a PI3K/Akt-dependent mechanism.-Chen, S., Mei, X., Yin, A., Yin, H., Cui, X.-B., Chen, S.-Y. Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting ß3-adrenergic receptor/mTORC1 signaling.


Assuntos
Tecido Adiposo Marrom/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Nucleares/deficiência , Receptores Adrenérgicos beta 3/metabolismo , Termogênese/genética , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Diferenciação Celular/genética , Proteínas do Sistema Complemento/metabolismo , Camundongos Knockout , Proteínas Nucleares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/genética
9.
Arch Oral Biol ; 85: 104-112, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29035721

RESUMO

OBJECTIVE: Stem cell-based tissue repair and regeneration require the regulation of cell migration and adhesion. As a regulator of cell polarization, Cdc42 (cell division control protein 42) plays a basic role at the initial stage of cell migration and adhesion. This study explores the effect of Cdc42 on the polarized migration and adhesion of hDPSCs (human dental pulp stem cells). DESIGN: HDPSCs were isolated from extracted third molars and transfected with siRNA targeted against Cdc42. Scratch wound assays and transwell assays were performed to detect the migration of human dental pulp stem cells. Polarization assays were applied to explore the polarized movement of Golgi bodies and nuclei. Western blot was used to examine the expression of related proteins. RESULTS: The expression of Cdc42 was knocked down by siRNA transfection, which inhibited the migration of hDPSCs in both the scratch wound assays and transwell assays. Meanwhile, the proportion of polarized hDPSCs during migration was also decreased, and the adhesion ability of hDPSCs was downregulated. Western blot demonstrated that these effects were dependent on FAK (focal adhesion kinase), ß-catenin and GSK3ß (Glycogen synthase kinase-3ß). CONCLUSION: Our study demonstrates that Cdc42 plays an essential role during the polarized movement and adhesion of hDPSCs.


Assuntos
Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Polpa Dentária/citologia , Proteína cdc42 de Ligação ao GTP/farmacologia , Adolescente , Western Blotting , Células Cultivadas , Citometria de Fluxo , Complexo de Golgi/efeitos dos fármacos , Humanos , Microscopia Confocal , Dente Serotino , Reação em Cadeia da Polimerase em Tempo Real , Transfecção , Adulto Jovem
10.
J Biol Chem ; 292(34): 14270-14278, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28659340

RESUMO

Smooth muscle cell (SMC) differentiation is essential for vascular development, and TGF-ß signaling plays a critical role in this process. Although long non-coding RNAs (lncRNAs) regulate various cellular events, their functions in SMC differentiation remain largely unknown. Here, we demonstrate that the lncRNA growth arrest-specific 5 (GAS5) suppresses TGF-ß/Smad3 signaling in smooth muscle cell differentiation of mesenchymal progenitor cells. We found that forced expression of GAS5 blocked, but knockdown of GAS5 increased, the expression of SMC contractile proteins. Mechanistically, GAS5 competitively bound Smad3 protein via multiple RNA Smad-binding elements (rSBEs), which prevented Smad3 from binding to SBE DNA in TGF-ß-responsive SMC gene promoters, resulting in suppression of SMC marker gene transcription and, consequently, in inhibition of TGF-ß/Smad3-mediated SMC differentiation. Importantly, other lncRNAs or artificially synthesized RNA molecules that contained rSBEs also effectively inhibited TGF-ß/Smad3 signaling, suggesting that lncRNA-rSBE may be a general mechanism used by cells to fine-tune Smad3 activity in both basal and TGF-ß-stimulated states. Taken together, our results have uncovered an lncRNA-based mechanism that modulates TGF-ß/Smad3 signaling during SMC differentiation.


Assuntos
Músculo Liso Vascular/metabolismo , RNA Longo não Codificante/metabolismo , RNA/metabolismo , Elementos de Resposta , Transdução de Sinais , Proteína Smad3/antagonistas & inibidores , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Ligação Competitiva , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Genes Reporter/efeitos dos fármacos , Hibridização in Situ Fluorescente , Isoquinolinas/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Proteínas Musculares/agonistas , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Conformação de Ácido Nucleico , Piridinas/farmacologia , Pirróis/farmacologia , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/química , Elementos de Resposta/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/química , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/química , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
11.
Clin Chim Acta ; 471: 29-37, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28502558

RESUMO

BACKGROUND: The sensitivities and specificities of biomarkers for gastric cancer are insufficient for clinical detection, and new diagnostics are therefore urgently required. METHODS: A discovery set of gastric cancer tissues was labeled with iTRAQ reagents, separated using SCX chromatography, and identified using LC-ESI-MS/MS. A validation set of gastric cancer tissues was used to confirm the expression levels of potential markers. RESULTS: The present study detected metastasis-associated protein 2 (MTA2) and Histone deacetylases 1 (HDAC1) proteins that were overexpressed in gastric cancer tissues compared with that in adjacent gastric tissue. The sensitivity and specificity of MTA2 in detecting 76 cases gastric cancers were 57.9% (95% CI: 46.5%-69.3%) and 55.3% (95% CI: 43.8%-66.7%), respectively. The sensitivity and specificity of HDAC1 were 61.8% (95% CI: 50.7%-73%) and 63.2% (95% CI: 52.1%-74.3%), respectively. The co-expression of MTA2 and HDAC1 in gastric cancer achieved 65.3% sensitivity (95% CI: 51.5%-79.1%) and 65.2% specificity (95% CI: 50.9%-79.5%), which was strongly associated with lymph node metastasis and TNM staging. CONCLUSION: The present findings indicated a tight correlation between the MTA2 and HDAC1 expression level and lymph node metastasis and TNM staging in gastric cancers. Therefore, MTA2 and HDAC1 might be predictors of lymph node metastasis phenotype and possible target molecule for anticancer drug design in human gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteômica , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Transcrição Genética , Sequência de Aminoácidos , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Feminino , Histona Desacetilase 1/química , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo , Histona Desacetilases/química , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sensibilidade e Especificidade , Neoplasias Gástricas/metabolismo
12.
Int J Offender Ther Comp Criminol ; 61(10): 1171-1190, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26472427

RESUMO

The nature of collective perception of prostitution is understudied in Canada. Except some rudimentary reports on the percentages of the key legal options, multivariate analysis has never been used to analyze the details of public opinion on prostitution. The current study explores the trend of public attitude toward prostitution acceptability in Canada over a 25-year span and examines the social determinants of the acceptability of prostitution, using structural equation modeling (SEM), which allows researchers to elaborate both direct and indirect effects (through mediating variables) on the outcome variable. Results show that the public has become more acceptant of prostitution over time. In addition, the less religious, less authoritarian, and more educated are more acceptant of prostitution than the more religious, more authoritarian, and less well educated. The effects of religiosity and authoritarianism mediate out the direct effects of age, gender, gender equality, marriage, marriage as an outdated institution, Quebec, race, and tolerance. The findings may serve as a reference point for the law reform regarding the regulation of prostitution in Canada.


Assuntos
Opinião Pública , Trabalho Sexual , Autoritarismo , Canadá , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Religião
13.
Hereditas ; 151(2-3): 28-37, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25040950

RESUMO

A recombinant inbred line (RIL) population from a cross between 'HH1B' and 'RSB02' (a deep-water rice variety with resistance to sheath blight) was planted in two locations for four different growing seasons. Seven traits were used to evaluate the disease severity, namely disease rating (DR), lesion length (LL), lesion height (LH), relative lesion length (RLL), relative lesion height (RLH), plant height (PH) and heading date (HD). Based on a linkage map of 163 simple sequence repeat (SSR) markers, a total of 37 QTLs were mapped on nine chromosomes. Additionally, 32 epistatic QTLs were identified, distributed on all the 12 chromosomes. The contribution of a single QTL's additive and epistatic effect was of low magnitude for most cases (from 0.39% to 24.62%). Among QTL × environment interaction test, 28 additive QTLs and six pairs of epistatic interactions were involved. Correlation analysis showed that DR had significant positive correlations with LL, RLL and RLH, but had a negative correlation with PH, two of six QTLs controlling DR were mapped in the same chromosome regions as the QTLs controlling PH. The alleles which can enhance disease resistance and increase PH are from the resistant parent 'RSB02', indicating that PH has certain effect on sheath blight resistance in the present study.


Assuntos
Meio Ambiente , Epistasia Genética/genética , Imunidade Inata/genética , Oryza/genética , Doenças das Plantas/genética , Locos de Características Quantitativas , Mapeamento Cromossômico , Cromossomos de Plantas , DNA de Plantas/genética , Ligação Genética , Oryza/crescimento & desenvolvimento , Doenças das Plantas/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...