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1.
Reproduction ; 150(1): 65-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25926693

RESUMO

Although the relationship between polymorphisms in microRNAs (miRNAs) and recurrent pregnancy loss (RPL) has been studied, there is very little data available in the literature. In the present study, we scanned 55 potentially functional polymorphisms in the miRNA coding region in Chinese women with unexplained RPL (URPL; no. 2011-10). The rs6505162 C>A in the MIR423 coding region was found to be significantly associated with the occurrence of human URPL. The rare A allele contributed to an increase in the expression of mature MIR423. C to A substitution in the polymorphism rs6505162 in pre-MIR423 repressed cell proliferation and migratory capacity. Further investigations showed that MIR423 could inversely regulate the expression of proliferation-associated 2 group 4 (PA2G4) by binding the 3'-UTR of PA2G4. Dual-luciferase assay indicated that the A allele in the polymorphism rs6505162 could more effectively suppress the expression of PA2G4 than the C allele could. Collectively, the present data suggest that rs6505162 C>A in pre-MIR423 may contribute to the genetic predisposition to RPL by disrupting the production of mature MIR423 and its target gene, which consequently interferes with MIR423 functioning.


Assuntos
Aborto Habitual/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Alelos , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Gravidez
2.
Reproduction ; 147(1): 91-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24149516

RESUMO

MiR199a was found to be differentially expressed in rat uteri between the prereceptive and receptive phase via microRNA (miRNA) microarray analysis in our previous study. However, the role of miR199a in rat embryo implantation remained unknown. In the study, northern blot results showed that the expression levels of miR199a were higher on gestation days 5 and 6 (g.d.5-6) in rat uteri than on g.d.3-4 and g.d.7-8. In situ localization of miR199a in rat uteri showed that miR199a was mainly localized in the stroma or decidua. The expression of miR199a was not significantly different in the uteri of pseudopregnant rats and evidently increased in the uteri of rats subjected to activation of delayed implantation and experimentally induced decidualization. Treatment with 17ß-estradiol or both 17ß-estradiol and progesterone significantly diminished miR199a levels. Gain of function of miR199a in endometrial stromal cells isolated from rat uteri inhibited cell proliferation and promoted cell apoptosis. Loss of function of miR199a displayed opposite roles on cell proliferation and apoptosis. Further investigation uncovered a significant inverse association between the expression of miR199a and growth factor receptor-bound protein 10 (Grb10), an imprinted gene, and miR199a could bind to the 3'UTR of Grb10 to inhibit Grb10 translation. In addition, in vivo analysis found that the immunostaining of GRB10 was attenuated in the stroma or decidua from g.d.4 to 6, contrary to the enhancement of miR199a. Collectively, upregulation of miR199a in rat uterus during the receptive phase is regulated by blastocyst activation and uterine decidualization. Enforced miR199a expression suppresses cell proliferation partially through targeting Grb10.


Assuntos
Implantação do Embrião/fisiologia , Proteína Adaptadora GRB10/metabolismo , MicroRNAs/metabolismo , Útero/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Proteína Adaptadora GRB10/genética , MicroRNAs/genética , Progesterona/farmacologia , Ratos , Ratos Sprague-Dawley , Útero/efeitos dos fármacos
3.
Front Endocrinol (Lausanne) ; 13: 917386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909537

RESUMO

Gestational diabetes mellitus (GDM), the most common medical pregnancy complication, has become a growing problem. More and more studies have shown that microRNAs are closely related to metabolic processes. The purpose of this paper is to investigate the role of up-regulation of miR-199a-5p expression in GDM. We found that miR-199a-5p was significantly up-regulated in the placenta of GDM patients compared with normal pregnant women, and expressed in placental villi. miR-199a-5p can regulate the glucose pathway by inhibiting the expression of methyl CpG-binding protein 2 (MeCP2) and down-regulating canonical transient receptor potential 3 (Trpc3). This suggests that miR-199a-5p may regulate the glucose pathway by regulating methylation levels, leading to the occurrence of GDM.


Assuntos
Diabetes Gestacional , MicroRNAs , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Feminino , Glucose/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta/metabolismo , Gravidez , Regulação para Cima
4.
J Asian Nat Prod Res ; 13(6): 492-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21623511

RESUMO

Two new neolignans, schilancifolignans D and E (1 and 2), together with eight known ones, were isolated from the leaves and stems of Schisandra lancifolia. The structures of 1 and 2 were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were tested for their anti-HIV-1 activities and cytotoxicity. Both showed significant potential cytotoxic ability and weak anti-HIV-1 activities.


Assuntos
Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Lignanas/isolamento & purificação , Schisandra/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , HIV-1/efeitos dos fármacos , Células HL-60 , Humanos , Células KB , Lignanas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
5.
Chem Pharm Bull (Tokyo) ; 58(5): 734-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20460806

RESUMO

Three new dibenzocyclooctadiene lignans, schilancifolignans A-C (1-3), together with thirteen known ones, were isolated from the leaves and stems of Schisandra lancifolia. The structures of 1-3 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compounds 1-3 were tested for their anti-human immunodeficiency virus-1 activities and showed weak bioactivities.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , HIV-1/efeitos dos fármacos , Lignanas/química , Lignanas/farmacologia , Schisandra/química , Fármacos Anti-HIV/isolamento & purificação , Ciclo-Octanos/isolamento & purificação , Humanos , Lignanas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química
6.
Diabetes Metab Syndr Obes ; 13: 3009-3034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32943895

RESUMO

PURPOSE: This study aimed to investigate the role of miR-21 expression in the reduction of placental function in GDM patients. MATERIALS AND METHODS: qRT-PCR was used to detect the differential expression of miR-21 in the serum of gestational diabetes mellitus (GDM) and normal pregnant women, and to verify the functional target gene PPAR-α of miR-21 by double fluorescence experiments. Cellular experiments were performed to verify the effect of PPAR-α on cell function. RESULTS: miR-21 is down-regulated in the serum and placenta of GDM patients compared to normal pregnant women. In the case of insulin resistance, miR-21-5p knockdown promoted glucose uptake, but no significant effect was found under physiological condition. Functional studies have shown that reduced PPAR-α expression can restore miR-21 knockdown-mediated cell growth and metastasis inhibition. Additionally, decreased expression of miR-21 but increased expression of -PPAR-α was observed in patients with GDM and GDM rats. CONCLUSION: The expression of the placental miR-21-5p, which inhibits cell growth and infiltration by up-regulating PPAR-α, is downregulated in pregnant GDM patients, which in turn may affect the placental function.

7.
Medicine (Baltimore) ; 98(43): e17438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651847

RESUMO

Recent genome-wide association studies (GWAS) indicated that polymorphisms in ADAMTS7 were associated with artery disease caused by atherosclerosis. However, the correlation between the ADAMTS7 polymorphism and plaque stability remains unclear. The objective of this study was to evaluate the association between 2 ADAMTS7 variants rs3825807 and rs7173743 and ischemic stroke or atherosclerotic plaque vulnerability.This research is an observational study. Patients with ischemic stroke and normal control individuals admitted to Beijing Tiantan Hospital from May 2014 to October 2017 were enrolled. High-resolution magnetic resonance imaging was used to distinguish vulnerable and stable carotid plaques. The ADAMTS7 SNPs were genotyped using TaqMan assays on real-time PCR system. The multivariate logistic regression analyses were used to adjust for multiple risk factors between groups.Three hundred twenty-six patients with ischemic stroke (189 patients with vulnerable plaque and 81 patients with stable plaque) and 432 normal controls were included. ADAMTS7 polymorphisms of both rs7173743 and rs3825807 were associated with carotid plaque vulnerability but not the prevalence of ischemic stroke. The T/T genotype of rs7173743 [odds ratio (OR) = 1.885, 95% confidence interval (CI) = 1.067-3.328, P = .028] and A/A genotype of rs3825807 (OR = 2.146, 95% CI = 1.163-3.961, P = .013) were considered as risk genotypes for vulnerable plaque susceptibility.In conclusion, ADAMTS7 variants rs3825807 and rs7173743 are associated with the risk for carotid plaque vulnerability.


Assuntos
Estenose das Carótidas/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Proteína ADAMTS7/sangue , Estenose das Carótidas/epidemiologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
8.
Am J Transl Res ; 8(2): 827-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27158372

RESUMO

BACKGROUND: Recent studies show inflammation-associated lymphangiogenesis (IAL) induced by vascular endothelial growth factor receptor 3 (VEGFR-3) pathway has a close relationship with chronic intestinal inflammation, and antilymphatic signaling pathways may repress IAL. However, whether the biologic function of lymphatic vessel is the same in severe acute intestinal inflammation still remain unknown. METHODS: C57BL/6 mice were administered with 5% of dextran sodium sulfate (DSS) in drinking water for 7 days to establish severe acute colitis (SAC) model. Chronic colitis (CC) model was established by three cycles of 2% DSS for 5 days following water for 5 days. Mice were treated with VEGFR-3 antibody once daily in SAC group, or once every 3 days in CC group. The colon inflammation, submucosal edema, lymphatic vessel (LV) density, LV size, lymph flow, cytokines and immune cells infiltration were detected. RESULTS: Both acute and chronic colitis resulted in a significant aggravation of colon inflammation in anti-VEGFR-3-treated mice, compared with PBS-treated colitis mice. Meanwhile, this was accompanied with decreased lymph drainage, increased submucosal edema, inflammatory cells infiltration and cytokines levels. In acute intestinal inflammation, significantly distorted and enlarged lymphatics were found but the LV number remained unchanged; not only significantly distorted and enlarged lymphatics but reduced LV number were found in chronic colitis. CONCLUSION: Blocking VEGFR-3 in acute and chronic colitis leads to deterioration of colon inflammation with impaired lymphatic function and different changes in LVs. In the therapy targeting VEGF-C/VEGFR-3 pathway for lymphangiogenesis, the phrase and severity of intestinal inflammation should be taken into account.

9.
Sci Rep ; 6: 32268, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27573367

RESUMO

MiR-98 expression was up-regulated in kidney in response to early diabetic nephropathy in mouse and down-regulated in muscle in type 2 diabetes in human. However, the expression prolife and functional role of miR-98 in human gestational diabetes mellitus (GDM) remained unclear. Here, we investigated its expression and function in placental tissues from GDM patients and the possible molecular mechanisms. The results showed that miR-98 was up-regulated in placentas from GDM patients compared with normal placentas. MiR-98 over-expression increased global DNA methylational level and miR-98 knockdown reduced global DNA methylational level. Further investigation revealed that miR-98 could inhibit Mecp2 expression by binding the 3'-untranslated region (UTR) of methyl CpG binding protein 2 (Mecp2), and then led to the expression dysregulation of canonical transient receptor potential 3 (Trpc3), a glucose uptake related gene. More importantly, in vivo analysis found that the expression level of Mecp2 and Trpc3 in placental tissues from GDM patients, relative to the increase of miR-98, was diminished, especially for GDM patients over the age of 35 years. Collectively, up-regulation of miR-98 in the placental tissues of human GDM is linked to the global DNA methylation via targeting Mecp2, which may imply a novel regulatory mechanism in GDM.


Assuntos
Diabetes Gestacional/genética , Regulação da Expressão Gênica , Proteína 2 de Ligação a Metil-CpG/genética , MicroRNAs/genética , Regulação para Cima , Regiões 3' não Traduzidas/genética , Adulto , Metilação de DNA , Feminino , Humanos , Recém-Nascido , Placenta/metabolismo , Gravidez , Canais de Cátion TRPC/genética
10.
FEBS Lett ; 588(23): 4438-47, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25448984

RESUMO

MiR-185 expression has been associated with many cancers. However, the roles of miR-185 in human breast cancer remain elusive. Here, we found that miR-185 expression was decreased in human breast cancer tissues compared with healthy tissue controls. Up-regulation of miR-185 inhibited breast cancer cell proliferation and invasion and vice versa. MiR-185 was shown to bind to the 3'-untranslated region (UTR) of vascular endothelial growth factor a (Vegfa), and a significant inverse correlation was found between miR-185 and Vegfa. Vegfa overexpression partially restored the inhibition of cell proliferation and invasion that was induced by miR-185, and vice versa. Additionally, Vegfa expression was found to be high in human breast cancer tissues. Thus, miR-185-mediated Vegfa targeting may be involved in breast cancer formation.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/genética , Apoptose/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica , Metástase Neoplásica
11.
Int J Dev Neurosci ; 31(7): 487-95, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23727134

RESUMO

Polycomb group (PcG) proteins are transcription regulatory proteins that control the expression of a variety of genes and the antero-posterior neural patterning from early embryogenesis. Although expression of PcG genes in the nervous system has been noticed, but the expression pattern of PcG proteins in early embryonic nervous system is still unclear. In this study, we analyzed the expression pattern of PRC1 complex members (BMI-1 and RING1B) and PRC2 complex members (EED, SUZ12 and EZH2) in early embryonic nervous system in mouse and human by Western blot and Immunohistochemistry. The results of Western blot showed that EED protein was significantly up-regulated with the increase of the day of pregnancy during the early embryogenesis in mouse. BMI-1 protein level was significantly increased from the day 10 of pregnancy, when compared with the day 9 of pregnancy. But the SUZ12, EZH2 and RING1B protein level did not change significantly. From the results of Immunohistochemistry, we found that the four PcG proteins were all expressed in the fetal brain and fetal spinal cord in mouse. In human, the expression of EED, SUZ12, and EZH2 was not significantly different in cerebral cortex and sacral spinal cord, but BMI-1 and RING1B expression was enhanced with the development of embryos in early pregnancy. Collectively, our findings showed that PRC1 and PRC2 were spatiotemporally expressed in brain and spinal cord of early embryos.


Assuntos
Padronização Corporal/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Sistema Nervoso/embriologia , Sistema Nervoso/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Fatores Etários , Animais , Proteínas de Ciclo Celular/metabolismo , Embrião de Mamíferos , Feminino , Feto , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Complexo Repressor Polycomb 1/metabolismo , Gravidez
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