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2.
Oncogene ; 39(21): 4183-4197, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32291412

RESUMO

CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a transmembrane glycoprotein that is highly expressed in tumor cells, particularly melanoma cells, and plays critical roles in tumor cell metastasis through the regulation of matrix metalloprotease (MMP) expression. In this study, we identified Fyn as a novel interacting protein of CD147. Fyn is a member of the Src family of nonreceptor tyrosine kinases that regulates diverse physiological processes, such as T lymphocyte differentiation, through the TCR signaling pathway. Our findings demonstrated that Fyn directly phosphorylates CD147 at Y140 and Y183. Two phosphospecific antibodies against Y140 and Y183 were developed to validate the phosphorylation of CD147 by Fyn. Moreover, the CD147-FF (Y140F/Y183F) mutation impaired the interaction between CD147 and GnT-V, leading to decreased CD147 glycosylation and membrane recruitment. In addition, CD147-FF significantly blocked MMP-9 expression as well as cell migration. Moreover, we found that Fyn is overexpressed in clinical melanoma tissues as well as in melanoma cell lines. Knockdown of Fyn expression markedly attenuated the malignant phenotype of melanoma cells in vitro and in vivo through downregulation of CD147 phosphorylation, indicating that Fyn/CD147 is a potential target molecule in melanoma treatment. Finally, through virtual screening, we identified amodiaquine as a potential inhibitor targeting the Fyn/CD147 axis. Amodiaquine treatment dramatically inhibited the phosphorylation of CD147 by Fyn, thus attenuating melanoma cell growth and invasion in vitro and in vivo, suggesting that amodiaquine is a promising inhibitor for melanoma treatment.


Assuntos
Basigina/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Transdução de Sinais , Substituição de Aminoácidos , Basigina/genética , Linhagem Celular Tumoral , Glicosilação , Humanos , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Melanoma/genética , Melanoma/patologia , Mutação de Sentido Incorreto , Metástase Neoplásica , Fosforilação/genética , Proteínas Proto-Oncogênicas c-fyn/genética
3.
J Nanosci Nanotechnol ; 20(2): 1260-1268, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383127

RESUMO

Nickel-cobalt layered double hydroxide nanosheets intercalated with sulfate anion were fabricated via a facile hydrothermal method and investigated as high-performance electrode materials for supercapacitors. The morphology and electrochemical properties of the obtained samples could be controlled by changing molar ratios of the Ni and Co precursors. NiCo-LDHs with Ni/Co molar ratio of 0.35:0.65 exhibited high specific capacitance of 1551.1 F/g at the current density of 1 A/g and good cycling stability of 84.0% retention after 1000 charge/discharge cycles. On this basic, aqueous asymmetric supercapacitor (AAS) was successfully constructed by using the Ni0.35Co0.65-LDHs as the positive electrode and the activated carbon as the negative electrode. The as-built AAS was able to work in a working voltage window of 0~1.4 V and exhibited outstanding electrochemical performance. The Ni0.35Co0.65-LDHs//KOH activated cotton-derived carbon (ACDC) AAS showed the highest specific capacitance of 157.5 F/g, the satisfactory capacitance retention of 78.62% after 5000 cycles, the maximum energy density of 42.88 Wh/kg, and preferable combination of energy density of 30.63 Wh/kg with power density of 4.9 kW/kg at a current density of 7 A/g.

5.
Front Chem ; 6: 138, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868550

RESUMO

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget, and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB, and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and grasp the types of calculations used in protein target fishing. In addition, we review the main features of these methods, programs and databases and provide a variety of examples illustrating the application of one or a combination of reverse screening methods for accurate target prediction.

6.
Cell Physiol Biochem ; 46(2): 442-450, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29614499

RESUMO

BACKGROUND/AIMS: Growing evidence has shown that miR-330-3p is closely related to the biological behavior of cancer, including proliferation, metastasis, and prognosis. However, there have been no reports on miR-330-3p expression and function in osteosarcoma. METHODS: Expression of miR-330-3p in osteosarcoma tissues and cell lines was examined by quantitative PCR. Effects of miR-330-3p on osteosarcoma cell proliferation were investigated in vitro with the Cell Counting Kit-8 colorimetric assay. Targets of miR-330-3p were identified by dual-luciferase reporter assay. RESULTS: The results showed that expression of miR-330 decreased in osteosarcoma tissues and cell lines. Prognosis of patients with high miR-330-3p expression was much better than that of those with low expression (P=0.001), and multivariate analysis suggested that miR-330-3p is an independent prognostic factor for osteosarcoma. In addition, miR-330-3p overexpression significantly inhibited the growth of MG-63 and U2OS osteosarcoma cells. Dual-luciferase reporter assay demonstrated that Bmi-1 was a direct target gene of miR-330-3p, and in a recovery experiment, miR-330-3p suppressed osteosarcoma cell proliferation by directly targeting Bmi-1. CONCLUSION: Our results suggest that miR-330-3p acts as a tumor suppressor by regulating Bmi-1 expression in osteosarcoma. Thus, miR-330-3p may represent a novel therapeutic target for the treatment of osteosarcoma.


Assuntos
Neoplasias Ósseas/patologia , MicroRNAs/metabolismo , Osteossarcoma/patologia , Complexo Repressor Polycomb 1/metabolismo , Regiões 3' não Traduzidas , Adulto , Antagomirs/metabolismo , Sequência de Bases , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Mutagênese Sítio-Dirigida , Osteossarcoma/genética , Osteossarcoma/mortalidade , Complexo Repressor Polycomb 1/química , Complexo Repressor Polycomb 1/genética , Prognóstico , Modelos de Riscos Proporcionais , Alinhamento de Sequência , Taxa de Sobrevida , Adulto Jovem
7.
Mol Cancer ; 16(1): 87, 2017 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-28476123

RESUMO

BACKGROUND: Estrogenic signals are suggested to have protection roles in the development of colorectal cancer (CRC). The G protein-coupled estrogen receptor (GPER) has been reported to mediate non-genomic effects of estrogen in hormone related cancers except CRC. Its expression and functions in CRC were investigated. METHODS: The expression of GPER and its associations with clinicopathological features were examined. The mechanisms were further investigated using cells, mouse xenograft models, and clinical human samples. RESULTS: GPER was significantly (p < 0.01) down regulated in CRC tissues compared with their matched adjacent normal tissues in our two cohorts and three independent investigations from Oncomine database. Patients whose tumors expressing less (n = 36) GPER showed significant (p < 0.01) poorer survival rate as compared with those with greater levels of GPER (n = 54). Promoter methylation and histone H3 deacetylation were involved in the down regulation of GPER in CRC cell lines and clinical tissues. Activation of GPER by its specific agonist G-1 inhibited proliferation, induced cell cycle arrest, mitochondrial-related apoptosis and endoplasmic reticulum (ER) stress of CRC cells. The upregulation of reactive oxygen species (ROS) induced sustained ERK1/2 activation participated in G-1 induced cell growth arrest. Further, G-1 can inhibit the phosphorylation, nuclear localization, and transcriptional activities of NF-κB via both canonical IKKα/ IκBα pathways and phosphorylation of GSK-3ß. Xenograft model based on HCT-116 cells confirmed that G-1 can suppress the in vivo progression of CRC. CONCLUSIONS: Epigenetic down regulation of GPER acts as a tumor suppressor in colorectal cancer and its specific activation might be a potential approach for CRC treatment.


Assuntos
Neoplasias Colorretais/genética , Epigênese Genética/genética , Neoplasias Hormônio-Dependentes/genética , Receptores Estrogênicos/genética , Receptores Acoplados a Proteínas-G/genética , Idoso , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Ciclopentanos/administração & dosagem , Estrogênios/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/patologia , Quinolinas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
8.
PLoS One ; 12(2): e0172323, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28245222

RESUMO

Heterogeneous information networks (e.g. bibliographic networks and social media networks) that consist of multiple interconnected objects are ubiquitous. Clustering analysis is an effective method to understand the semantic information and interpretable structure of the heterogeneous information networks, and it has attracted the attention of many researchers in recent years. However, most studies assume that heterogeneous information networks usually follow some simple schemas, such as bi-typed networks or star network schema, and they can only cluster one type of object in the network each time. In this paper, a novel clustering framework is proposed based on sparse tensor factorization for heterogeneous information networks, which can cluster multiple types of objects simultaneously in a single pass without any network schema information. The types of objects and the relations between them in the heterogeneous information networks are modeled as a sparse tensor. The clustering issue is modeled as an optimization problem, which is similar to the well-known Tucker decomposition. Then, an Alternating Least Squares (ALS) algorithm and a feasible initialization method are proposed to solve the optimization problem. Based on the tensor factorization, we simultaneously partition different types of objects into different clusters. The experimental results on both synthetic and real-world datasets have demonstrated that our proposed clustering framework, STFClus, can model heterogeneous information networks efficiently and can outperform state-of-the-art clustering algorithms as a generally applicable single-pass clustering method for heterogeneous network which is network schema agnostic.


Assuntos
Análise por Conglomerados , Biologia Computacional/métodos , Mapeamento de Interação de Proteínas/métodos , Algoritmos , Congressos como Assunto , Coleta de Dados , Mineração de Dados , Serviços de Informação , Análise dos Mínimos Quadrados , Aprendizado de Máquina , Filmes Cinematográficos , Estatística como Assunto
9.
Medicine (Baltimore) ; 95(40): e4982, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27749554

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Previous publications have investigated the association of NOS1 and ABCB1 polymorphisms with PD risk. However, those studies have provided some contradictory results. METHODS: Literature searches were performed using PubMed, Embase, PDgene, China National Knowledge Infrastructure database, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to evaluate the strength of association. RESULTS: The analysis results indicated that NOS1 exon18 polymorphism was associated with developing PD in 4 genetic models (allelic: OR = 1.25, 95%CI 1.09-1.44, P = 0.001; homozygous: OR = 1.79, 95%CI 1.32-2.45, P < 0.001; recessive: OR = 1.70, 95%CI 1.26-2.28, P < 0.001; dominant: OR = 1.22, 95%CI 1.02-1.46, P = 0.03), whereas exon29 polymorphism was not correlated to PD susceptibility. In addition, ABCB1 1236C/T polymorphism was related to PD in the recessive (OR = 0.80, 95%CI 0.66-0.97, P = 0.025) and overdominant (OR = 1.21, 95%CI 1.03-1.43, P = 0.02) models, which might indicate the opposite effects of 2 minor variants of this locus on Parkinson's disease. However, this associated result was not robust enough to withstand statistically significant correction. On the other hand, no association was found between ABCB1 3435C/T polymorphism and the predisposition to PD in 5 genetic models, and such an absence of relationship was further confirmed by subgroup analysis in Caucasians and Asians. Whether the polymorphisms of these 4 loci were linked to PD or not, our study provided some interesting findings that differ from the previous results with regard to their genetic susceptibility. CONCLUSION: The NOS1 exon18 and ABCB1 1236C/T variants might play a role in the risk of Parkinson's disease, whereas NOS1 exon29 and ABCB1 3435C/T polymorphisms might not contribute to PD susceptibility.


Assuntos
Óxido Nítrico Sintase Tipo I/genética , Doença de Parkinson/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Alelos , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Predisposição Genética para Doença , Humanos , Polimorfismo Genético
10.
Meta Gene ; 9: 97-103, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27331013

RESUMO

PURPOSE: Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system with a strong genetic component. Previous studies have reported that the association of EVI5 rs11808092, CD58 rs2300747, and CIITA rs3087456 polymorphisms with the susceptibility to MS. However, the results were inconsistent. Thus, we conducted this meta-analysis to provide a more accurate estimation of the association between any of these polymorphisms and MS risk. METHODS: The PubMed, Embase, Chinese National Knowledge Infrastructure, Wan Fang databases and MSGene were used to search all potentially relevant studies. The odds ratio (OR) with 95% confidence interval (CI) was used to investigate the associations between these three polymorphisms and MS risk. RESULTS: 16 independent case-control studies from 12 publications were finally included into this meta-analysis. The results showed that EVI5 rs11808092 polymorphism was related with increasing the development of MS under five genetic models (allelic: OR = 1.17, 95% CI = 1.10-1.24, P < 0.01; homozygous: OR = 1.37, 95% CI = 1.18-1.59, P < 0.01; heterozygous: OR = 1.16, 95% CI = 1.07-1.26, P < 0.01; recessive: OR = 1.28, 95% CI = 1.11-1.48, P < 0.01; and dominant: OR = 1.19, 95% CI = 1.11-1.48, P < 0.01). CD58 rs2300747 polymorphism was found to be associated with decreasing MS risk in three genetic models (allelic: OR = 0.86, 95% CI = 0.78-0.94, P < 0.01; heterozygous: OR = 0.85, 95% CI = 0.76-0.94, P < 0.01, and dominant: OR = 0.84, 95% CI = 0.76-0.93, P < 0.01). However, this meta-analysis indicated that CIITA rs3087456 polymorphism was not related to multiple sclerosis. CONCLUSIONS: The mutant alleles of EVI5 rs11808092 polymorphism may increase the susceptibility to MS while those of CD58 rs2300747 polymorphism may decrease MS risk. In addition, CIITA rs3087456 polymorphism might not be associated with MS.

11.
Environ Res ; 148: 72-78, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27035923

RESUMO

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are attracting more and more attention for the neurodevelopment toxicity effects. We evaluated the concentrations of 15 individual OH-PBDEs and 3 bromophenol (BRP) congeners in 30 mother-newborn paired placenta, breast milk, fetal cord blood, and neonatal urine samples collected from South China. The geometric mean (GM) concentrations of ∑OH-PBDEs were 37.6, 61.3, and 76.8pgg(-1) ww in placenta, breast milk, and cord blood, respectively. The GM concentrations of ∑BRPs were 47.6, 119, and 30.2pgg(-1) ww in placenta, breast milk, and cord blood, respectively. The GM concentrations of ∑OH-PBDEs and ∑BRPs in neonatal urine were 72.0 and 79.8pgml(-1), respectively. Of the 15 OH-PBDE congeners analyzed, the three most frequently detected congeners were 2'-OH-BDE-68 (72.1%), 6-OH-BDE-47 (67.6%), and 2'-OH-BDE-28 (65.8%). The estimated daily intake (EDI) of OH-PBDEs for the breast-fed infants was 9.31±4.00ngkg(-1) bw day. The accumulation of OH-PBDEs in newborns was much lower than the estimated lowest observed-effect concentration (LOEC) of neurotoxicity. The present study provided the first systematic fundamental data that exposure to OH-PBDEs for newborn and their mothers in South China.


Assuntos
Poluentes Ambientais/análise , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Troca Materno-Fetal , Adulto , China , Monitoramento Ambiental , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Feminino , Sangue Fetal/química , Éteres Difenil Halogenados/sangue , Éteres Difenil Halogenados/urina , Humanos , Hidroxilação , Recém-Nascido , Exposição Materna , Leite Humano/química , Fenóis/análise , Fenóis/sangue , Fenóis/urina , Placenta/química , Gravidez , Medição de Risco , Adulto Jovem
12.
Oncotarget ; 7(11): 12568-81, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26871469

RESUMO

There is an urgent clinical need for targeted therapy approaches for triple-negative breast cancer (TNBC) patients. Increasing evidences suggested that the expression of estrogen-related receptor alpha (ERRα) was correlate with unfavorable clinical outcomes of breast cancer patients. We here show that inhibition of ERRα by its inverse agonist XCT-790 can suppress the proliferation, decrease G2/M phases, and induce mitochondrial-related apoptosis of TNBC cells. XCT-790 elevates the proteins related to endoplasmic reticulum (ER) stress such as ATF4/6, XBT-1 and CHOP. It also increases the expression of growth inhibition related proteins such as p53 and p21. Further, XCT-790 can increase the generation of reactive oxygen species (ROS) in TNBC cells mainly through inhibition of SOD1/2. While ROS scavenger NAC abolishes XCT-790 induced ER-stress and growth arrest. XCT-790 treatment can rapidly activate the signal molecules including ERK1/2, p38-MAPK, JNK, Akt, p65, and IκBα, while NAC attenuates effects of XCT-790 induced phosphorylation of ERK1/2, p38-MAPK and Akt. Further, the inhibitors of ERK1/2, JNK, Akt, and NF-κB attenuate XCT-790 induced ROS generation. These data suggest that AKT/ROS and ERK/ROS positive feedback loops, NF-κB/ROS, and ROS/p38-MAPK, are activated in XCT-790 treated TNBC cells. In vivo experiments show that XCT-790 significantly suppresses the growth of MDA-MB-231 xenograft tumors, which is associated with up regulation of p53, p21, ER-stress related proteins while down regulation of bcl-2. The present discovery makes XCT-790 a promising candidate drug and lays the foundation for future development of ERRα-based therapies for TNBC patients.


Assuntos
Antineoplásicos/farmacologia , Nitrilos/farmacologia , Receptores Estrogênicos/antagonistas & inibidores , Tiazóis/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Espécies Reativas de Oxigênio , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Arch Toxicol ; 89(8): 1371-81, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25119493

RESUMO

More and more evidences indicate that endocrine disruptor chemicals such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis. Although the gut is in direct contact with orally ingested BPA, effects of BPA on occurrence and development of colorectal cancer remain an unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8) M) or greater (10(-5) M) concentrations of BPA were compared with responses of a control group. Proteomic study revealed that more than 56 proteins were modulated following exposure to BPA, which are relevant to structure, motility and proliferation of cells, production of ATP, oxidative stress, and protein metabolism. Further studies revealed that BPA increased migration and invasion and triggered transformations from epithelial to mesenchymal transitions (EMTs) of colorectal cancer cells, which was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin with a concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the expression of transcription factor Snail. Furthermore, signal AKT/GSK-3ß-mediated stabilization of Snail is involved during BPA-induced EMT of colon cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar and greater concentrations modulates the protein profiles and promotes the metastasis of colorectal cancer cells via induction of EMT.


Assuntos
Compostos Benzidrílicos/toxicidade , Neoplasias Colorretais/patologia , Disruptores Endócrinos/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fenóis/toxicidade , Proteoma/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Metástase Neoplásica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
14.
Rev Sci Instrum ; 85(11): 113701, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25430114

RESUMO

To date, rotating mirror (RM) cameras still serve as indispensable imaging equipment for the diagnosis of microsecond transient processes due to their excellent characteristics. This paper, for upgrading the optical information capacity of the cameras, presents the new optical acceleration principle to increase the framing frequency or scanning velocity, the new design theory without principle errors instead of the classical theories with some flaws in principle to have applied to design our simultaneous streak and framing rotating mirror camera with continuous access, and the new rotating mirror with novel structure, made of an aluminum alloy, to have considerably reduced lateral deformation of the RM and improved the performance of the camera.

15.
Biochim Biophys Acta ; 1840(9): 2663-73, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24909818

RESUMO

BACKGROUND: Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study. METHODS: We utilized proteomic study to identify the protein expression changes of Sertoli TM4 cells treated with 10(-8)M and 10(-5)M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis. RESULTS: Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10(-8)M and 10(-5)M BPA, respectively, for 24h. Exposure to 10(-5)M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10(-8)M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages. CONCLUSIONS: Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism. GENERAL SIGNIFICANCE: Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.


Assuntos
Poluentes Ocupacionais do Ar/farmacologia , Compostos Benzidrílicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Fenóis/farmacologia , Proteoma/biossíntese , Células de Sertoli/metabolismo , Animais , Linhagem Celular , Metabolismo Energético/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Células de Sertoli/citologia
16.
Sci China Life Sci ; 57(3): 315-326, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24532457

RESUMO

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) tumorigenesis. However, the mechanism(s) connecting EBV infection and NPC remain unclear. Recently, a new class of EBV microRNAs (miRNAs) has been described. To determine how EBV miRNAs control the expression of host genes, and to understand their potential role in NPC tumorigenesis, we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues. We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC. Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC. A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated, suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis. An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.


Assuntos
Redes Reguladoras de Genes , Herpesvirus Humano 4/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Transcriptoma , Regiões 3' não Traduzidas/genética , Animais , Western Blotting , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Epitélio/metabolismo , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Células HEK293 , Herpesvirus Humano 4/fisiologia , Interações Hospedeiro-Patógeno/genética , Humanos , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/virologia , Nasofaringe/metabolismo , Nasofaringe/patologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Contendo Repetições de beta-Transducina/genética , Proteínas Contendo Repetições de beta-Transducina/metabolismo
17.
Toxicol Lett ; 226(1): 81-9, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24495410

RESUMO

Sertoli cells play a pivotal role in supporting proliferation of germ cells and differentiation during spermatogenesis in mammals. Nanomolar concentrations of Bisphenol A (BPA) can significantly stimulate the proliferation of mouse immature Sertoli (TM4) cells. However, mechanisms by which BPA caused these effects were still unclear. In the present study, an inverse U-shaped curve was observed when treating TM4 cells with increasing doses of BPA: 1 to 10nM BPA significantly stimulated the proliferation of TM4 cells and increased the proportion of cells in S phase; >1 µM BPA caused lesser proliferation of cells. Exposure of TM4 cells to G15 or ICI 182,780, which are specific antagonists of GPR30 and estrogen receptor α/ß (ERα/ß), respectively, abolished BPA-induced proliferation of cells, which suggests that both GPR30 and ERα/ß were involved in the observed effects of BPA. Furthermore, exposure to BPA caused rapid (5 min) activation of ERK1/2 via both GPR30 and ERα/ß. Blocking the GPR30/EGFR signal transduction pathway by antagonists suppressed both phosphorylation of ERK and BPA-induced cell proliferation. BPA up-regulated mRNA and protein expression of GPR30 in a concentration-dependent manner. In summary, the results reported here indicated that activating ERK1/2 through GPR30 and ERα/ß is involved in low doses of BPA that promoted growth of Sertoli TM4 cells. The GPR30/EGFR/ERK signal is the downstream transduction pathway in BPA-induced proliferation of TM4 Sertoli cells.


Assuntos
Compostos Benzidrílicos/toxicidade , Proliferação de Células/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Receptor alfa de Estrogênio/efeitos dos fármacos , Receptor beta de Estrogênio/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fenóis/toxicidade , Receptores Acoplados a Proteínas-G/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Ativação Enzimática , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/metabolismo , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Masculino , Camundongos , Fosforilação , RNA Mensageiro/metabolismo , Receptores Estrogênicos , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/metabolismo , Fase S/efeitos dos fármacos , Células de Sertoli/enzimologia , Células de Sertoli/patologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Regulação para Cima
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 39(1): 91-5, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24473392

RESUMO

Long non-coding RNAs (lncRNAs) are a group of endogenous RNA molecules which exceed 200 nt in length, lack complete specific open reading frame, and completely lack or possessvery limited protein-coding capacity. Recent studies have revealed that lncRNAs participate in critical processes such as genomic imprinting, cell differentiation, and immune reaction, etc. lncRNAs regulate gene expression at the epigenetic, transcriptional and post-transcriptional levels by modulating chromatin remodeling and histone modifications, interfering the transcription, regulating patterns of alternative splicing, generating small RNAs, and modulating protein activation and localization. Through their numerous functions, lncRNAs play critical roles in the growth, development, senescence, death, and other important physiological and pathological processes. Further investigation into the regulation of gene expression mediated by lncRNAs will be of great value in the thorough understanding of pathogenies and provide new molecular markers and drug targets of diseases.


Assuntos
Expressão Gênica , RNA Longo não Codificante , Processamento Alternativo , Montagem e Desmontagem da Cromatina , Fases de Leitura Aberta , Proteínas
19.
Zhongguo Gu Shang ; 26(2): 158-61, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23678767

RESUMO

OBJECTIVE: To investigate the effect of operative treatment for anteromedial facet fracture of the coronoid process of ulna,and to study its surgical exposures and fixation techniques. METHODS: From March 2005 to March 2010,18 patients with anteromedial facet fracture of the coronoid process of ulna were treated with open reduction and internal fixation. There were 12 males and 6 females with an average age of 37.8 years. A single midline posterior incision was used to expose the entire elbow joint. After elevating the full-thickness skin flaps, a lateral incision was made to expose and repair the lateral collateral ligament. Three intervals in the flexor-pronator musculature were used to gain access to the coronoid,depending on the size of the fracture fragment and the planned fixation technique. Fractures were fixed by using mini-plate or with screws. The therapeutic effects were evaluated by Mayo Elbow Performance Score (MEPS) and system of Broberg & Morrey. RESULTS: Seventeen patients were followed up, no patient complained pain and elbow unstable at a mean follow-up period of 38 months(1 to 6 years). The fractures were clinically healed at an average time of 11.6 weeks(ranged from 8 to 16 weeks). The average MEPS was 95.4+/-4.6 (ranged, 82 to 100). The average functional rating of system of Broberg & Morrey was 92.3+/-5.8 (ranged,75 to 100). CONCLUSION: Open reduction and internal fixation is effective to reach anatomical reduction and strong fixation for the treatment of anteromedial facet fracture of the coronoid process of ulna.


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas da Ulna/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas da Ulna/fisiopatologia
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