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1.
Genes (Basel) ; 15(4)2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38674428

RESUMO

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for the genetic elements shared between PCOS and depression. METHODS: Differentially expressed genes (DEGs) were screened out through GEO2R using the PCOS and depression datasets in NCBI. Protein-protein interaction (PPI) network analysis and enrichment analysis were performed to identify the potential hub genes. After verification using other PCOS and depression datasets, the associations between key gene polymorphism and comorbidity were further studied using data from the UK biobank (UKB) database. RESULTS: In this study, three key genes, namely, SNAP23, VTI1A, and PRKAR1A, and their related SNARE interactions in the vesicular transport pathway were identified in the comorbidity of PCOS and depression. The rs112568544 at SNAP23, rs11077579 and rs4458066 at PRKAR1A, and rs10885349 at VTI1A might be the genetic basis of this comorbidity. CONCLUSIONS: Our study suggests that the SNAP23, PRKAR1A, and VTI1A genes can directly or indirectly participate in the imbalanced assembly of SNAREs in the pathogenesis of the comorbidity of PCOS and depression. These findings may provide new strategies in diagnosis and therapy for this comorbidity.


Assuntos
Depressão , Síndrome do Ovário Policístico , Mapas de Interação de Proteínas , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/epidemiologia , Humanos , Feminino , Depressão/genética , Depressão/epidemiologia , Mapas de Interação de Proteínas/genética , Proteínas Qb-SNARE/genética , Comorbidade , Proteínas Qc-SNARE/genética , Polimorfismo de Nucleotídeo Único , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Biologia Computacional/métodos , Predisposição Genética para Doença
2.
Asia Pac J Clin Nutr ; 31(1): 97-107, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35357108

RESUMO

BACKGROUND AND OBJECTIVES: The present study aimed to investigate the hypothesis that dietary amino acid intakes are associated with the risk of sarcopenia through a community-based observational study. METHODS AND STUDY DESIGN: A total of 1,140 participants (72.7±6.3 y) were recruited from an annual health check-up program in Qingdao, China. Skeletal muscle mass, muscle mass functions and biochemical parameters were measured by standard methods. Dietary intake was assessed by 3-day, 24-hour food records. The odds ratios (ORs) and 95% confidence intervals (CIs) of sarcopenic risk across quartiles of amino acid intakes were calculated using a multivariable- adjusted logistic regression model. Generalized linear models were used to assess the associations between dietary amino acid intakes and muscle mass functions. RESULTS: The prevalence of sarcopenia was 4.1%. Compared with the lowest category intake, the highest category of branched chain amino acids (BCAAs) (OR=0.11; 95% CI: 0.01, 0.90; p for trend=0.119), isoleucine (OR=0.11; 95% CI: 0.01, 0.89; p for trend=0.122) and tryptophan (OR=0.10; 95% CI: 0.01, 0.87; p for trend=0.176) was negatively correlated with sarcopenic risk with adjustment for potential confounding factors. Generalized linear model analysis showed that gait speed was positively correlated with dietary intakes of lysine, threonine, leucine, valine, tryptophan, BCAAs and aromatic amino acids (p<0.05). CONCLUSIONS: Higher intakes of BCAAs were associated with a lower risk of sarcopenia, which might beneficially protect against sarcopenia and improve physical function of the elderly.


Assuntos
Sarcopenia , Idoso , Aminoácidos de Cadeia Ramificada/metabolismo , Dieta , Humanos , Razão de Chances , Fatores de Risco , Sarcopenia/epidemiologia , Sarcopenia/prevenção & controle
3.
Nanotoxicology ; 15(3): 366-379, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33455495

RESUMO

Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.


Assuntos
Ferroptose/efeitos dos fármacos , Ferro/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro/química , Morte Celular/efeitos dos fármacos , Citoplasma/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
4.
Mol Cancer ; 18(1): 123, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399034

RESUMO

Piwi interacting RNAs (piRNAs) constitute novel small non-coding RNA molecules of approximately 24-31 nucleotides in length that often bind to members of the piwi protein family to play regulatory roles. Recently, emerging evidence suggests that in addition to the mammalian germline, piRNAs are also expressed in a tissue-specific manner in a variety of human tissues and modulate key signaling pathways at the transcriptional or post-transcriptional level. In addition, a growing number of studies have shown that piRNA and PIWI proteins, which are abnormally expressed in various cancers, may serve as novel biomarkers and therapeutic targets for tumor diagnostics and treatment. However, the functions of piRNAs in cancer and their underlying mechanisms remain incompletely understood. In this review, we discuss current findings regarding piRNA biogenetic processes, functions, and emerging roles in cancer, providing new insights regarding the potential applications of piRNAs and piwi proteins in cancer diagnosis and clinical treatment.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Animais , Biomarcadores Tumorais , Epigênese Genética , Perfilação da Expressão Gênica , Histonas , Humanos , Modelos Biológicos , Neoplasias/metabolismo , RNA Interferente Pequeno/metabolismo
5.
Toxicol In Vitro ; 59: 263-274, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31029784

RESUMO

Oxidative stress is usually considered to be a common mechanism by which particulate matter (PM) exposure induces adverse effects. However, the further biological events such as organelle dysfunction following oxidative stress remain to be explored. In this study, we applied high-content screening (HCS) technique to investigate the toxicological effects of carbon black (CB), diesel exhaust particle (DEP) and PM2.5 on oxidative stress and organelle function in human bronchial epithelial cell (16HBE), human embryo lung fibroblast cell (HELF) and human umbilical vein endothelial cell (HUVEC) which were used to represent distinct regions of the lung, and compared the toxicity impacts of different PMs and the sensitiveness of cell lines. We found three types of PMs induced mitochondrial dysfunction in three cell lines and lysosomal alkalinization in HUVEC while only CB triggered endoplasmic reticulum (ER) stress in 16HBE and HUVEC, and oxidative stress might mediate these processes. Moreover, CB basically exhibited more potent toxicity compared with DEP and PM2.5, which might be attributed to its less oxygen content. Finally, the finding that PMs-induced toxicity impacts exhibited a cell-type dependent manner might provide some information to help to understand the sensitivity of different tissue in the lung.


Assuntos
Retículo Endoplasmático/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Humanos , Organelas/efeitos dos fármacos
6.
Artigo em Inglês | MEDLINE | ID: mdl-28191021

RESUMO

Traditional Chinese Marine Medicine (TCMM) represents one of the medicinal resources for research and development of novel anticancer drugs. In this study, to investigate the presence of anticancer activity (AA) displayed by cold or hot nature of TCMM, we analyzed the association relationship and the distribution regularity of TCMMs with different nature (613 TCMMs originated from 1,091 species of marine organisms) via association rules mining and phylogenetic tree analysis. The screened association rules were collected from three taxonomy groups: (1) Bacteria superkingdom, Phaeophyceae class, Fucales order, Sargassaceae family, and Sargassum genus; (2) Viridiplantae kingdom, Streptophyta phylum, Malpighiales class, and Rhizophoraceae family; (3) Holothuroidea class, Aspidochirotida order, and Holothuria genus. Our analyses showed that TCMMs with closer taxonomic relationship were more likely to possess anticancer bioactivity. We found that the cluster pattern of marine organisms with reported AA tended to cluster with cold nature TCMMs. Moreover, TCMMs with salty-cold nature demonstrated properties for softening hard mass and removing stasis to treat cancers, and species within Metazoa or Viridiplantae kingdom of cold nature were more likely to contain AA properties. We propose that TCMMs from these marine groups may enable focused bioprospecting for discovery of novel anticancer drugs derived from marine bioresources.

7.
J Med Virol ; 89(4): 672-684, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27589693

RESUMO

The prominent feature of human cytomegalovirus (HCMV) is cell tropism specificity for human fetal nervous system, which leads to severe fetal nervous system damage especially in first-trimester gestation. In this study, human astrocytes isolated from fetal brain were infected with HCMV AD169 and whole genome transcriptome profile was performed. The results showed that the gene expression of interferon stimulated genes (ISGs), chemokine and chemokine receptors were significantly up-regulated (P < 0.01). The antiviral replication effects of IFIT1 (Interferon-induced protein with tetratricopeptide repeats 1, Fc = 148.17) was investigated. Lentivirus with IFIT1 overexpression or knockdown was transduced into astrocytes, respectively. The viral mRNA, protein expression and HCMV titers were determined. The results showed that IE1, IE2, pp65, and viral titers were significantly decreased in IFIT1 overexpression group and enhanced in the knockdown group compared with control one (P < 0.01). Taken together, this study revealed IFIT1 played an important antiviral role in HCMV infected fetal astrocytes. The prominent feature of human cytomegalovirus (HCMV) is cellular tropism specificity for human fetal brain nervous system leading to severe fetal nervous damage especially in first-trimester gestation. In this study, human astrocytes isolated from first-trimester fetal brain were infected with HCMV AD169 and IFIT1 was studied for its antiviral replication effects. The results provided insights into the function of IFIT1 as a key factor in antiviral defense contributing to development of targeted therapeutics to fetal brain with HCMV infection. J. Med. Virol. 89:672-684, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Astrócitos/imunologia , Astrócitos/virologia , Proteínas de Transporte/metabolismo , Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Replicação Viral , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/genética , Células Cultivadas , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Gravidez , RNA Viral/análise , Proteínas de Ligação a RNA , Carga Viral , Proteínas Virais/análise
8.
J Zhejiang Univ Sci B ; 16(9): 757-62, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26365117

RESUMO

Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 (ATF5) was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulfite-specific polymerase chain reaction (PCR) sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR (qRT-PCR) was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually decreased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues (P<0.05). There was also a significant difference between well-differentiated glioma and poorly differentiated glioma (P<0.05). ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues (P<0.05). This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma.


Assuntos
Fatores Ativadores da Transcrição/genética , Neoplasias Encefálicas/genética , Metilação de DNA/genética , Epigênese Genética/genética , Glioma/genética , Regiões Promotoras Genéticas/genética , Sequência de Bases , Humanos , Dados de Sequência Molecular , Regulação para Cima/genética
9.
Intractable Rare Dis Res ; 4(2): 98-104, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25984429

RESUMO

Cell therapy is a potential approach for treatment of strokes. Mesenchymal stem cells (MSCs) are a potential cell source for clinical use because they are safe and easy to obtain. A peptide solution can promote neural regeneration. Previously, such a solution was stereotactically injected into the brain of rats with cerebral infarction, resulting in improvement in the animal's neurological function and reduction in the infarction volume, but the injury was relatively severe. The current study established a rat model of cerebral ischemia-reperfusion (I/R) injury. MSCs isolated from Wharton's jelly of human umbilical cords (HUMSCs) were injected intravenously immediately after cerebral I/R injury(3 × 10(6) cells per rat). Twenty-four h and 14 d after surgery, animal behavior was evaluated using the Rogers test and infarct lesion volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining. Fourteen d after surgery, brain tissues were collected at 14 d to study migration/implantation of HUMSCs, cellular proliferation, neural regeneration and astrocyte activation. Compared to cerebral I/R injury alone, HUMSC treatment improved function at 14 d after surgery, with no reduction in infarct volume or migration or implantation of cells into the damaged brain areas. Nevertheless, 14 d after surgery, HUMSC administration increased cellular proliferation and the level of neurofilament 200 level and decreased the level of glial fibrillary acidic protein. After cerebral I/R injury, acute intravenous administration of HUMSCs could promote recovery by activating endogenous neural regeneration and inhibiting astrocyte activation, without migration and implantation directly into lesions.

10.
Neurochem Res ; 39(12): 2407-18, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25293581

RESUMO

Human cytomegalovirus (HCMV) infections are the leading cause of viral induced birth defects, affecting the central nervous system (CNS) primarily. Fetal CNS is especially vulnerable to CMV induced injury. As HCMV permissive cells, astrocytes are responsible for major glutamate transport and regulate extracellular levels of glutamate avoiding its accumulation which is implicated in neurodegenerative disorders. In this study, highly purified astrocytes isolated from human first trimester aborted fetal brain were infected with HCMV AD169, glutamate uptake function was detected by (3)H labeling technic, and the expression level alterations of glutamate transporters (GLAST, GLT-1), glutamine synthetase (GS) and its activity were also investigated. Protein kinases C (PKC) inhibitor treatment was to identify whether PKC signalling involved in regulating glutamate uptake, protein expression of GLAST, GLT-1, GS and GS activity. Results indicated HCMV AD169 infection could modulate glutamate uptake, expression levels of GLAST, GLT-1, GS and it activity through PKC signalling, suggesting a great susceptibility of human fetal astrocytes to HCMV infection, which significantly alters the uptake and metabolism of an important excitatory amino acid, glutamate, may be a potential mechanism for HCMV associated neurological disease, and an effective therapeutic target in neural diseases.


Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Astrócitos/metabolismo , Citomegalovirus/fisiologia , Feto/metabolismo , Ácido Glutâmico/metabolismo , Feto/citologia , Humanos
11.
Protein Expr Purif ; 101: 99-105, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24955549

RESUMO

M-IL-2((88)Arg, (125)Ala) is a fusion protein comprising melittin genetically linked to a mutant human interleukin 2((88)Arg, (125)Ala). In this study, we constructed an expression system of M-IL-2((88)Arg, (125)Ala) in Pichia pastoris: GS115/pPICZα A/M-IL-2((88)Arg, (125)Ala), and achieved the high-level expression of the fusion protein. The maximum yield of the fusion protein M-IL-2((88)Arg, (125)Ala) reached up to 814.5mg/L, higher than the system in Escherichiacoli. The fusion protein was purified by means of ammonium sulfate fractionation, dialysis and nickel ion affinity chromatography. The molecular weight of the fusion protein is about 26kDa, conforming the theoretical value. And M-IL-2((88)Arg, (125)Ala) possesses strong antigen-specificity by Western blot detection. Bioassay results indicated that the fusion protein could directly inhibit the growth of human ovarian cancer SKOV3 cells and Hela cells in vitro. This study provides an alternative strategy for large-scale production of bioactive M-IL-2((88)Arg, (125)Ala) using P. pastoris as an expression host and paves the way to clinical practice.


Assuntos
Interleucina-2/genética , Meliteno/genética , Neoplasias Ovarianas/tratamento farmacológico , Pichia/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia de Afinidade , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Expressão Gênica , Vetores Genéticos/genética , Células HeLa , Humanos , Dados de Sequência Molecular , Pichia/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética
12.
Virol J ; 10: 42, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23369640

RESUMO

BACKGROUND: To understand the prevalence and characteristics of human cytomegalovirus (HCMV) infection in children in the Weifang area, and to provide information for its prevention and treatment. METHODS: A comprehensive survey was performed from 2009 to 2012 in 7582 children from birth to 6 years of age hospitalized in the Maternity and Child Health Hospital of Weifang. ELISA HCMV serology results and survey data were analyzed by age group and socio-economic level. The infection rates were based on IgG and IgM serology. RESULTS AND CONCLUSIONS: The overall infection rate from IgG and IgM in the Weifang area from 2009 to 2012 was 42.5% (3496/7582), among which 34.2% were HCMV-IgG positive, suggesting past infection. Overall, the probability of active HCMV infection showed no gender difference in any age group (P >0.05). Recent infections centered on the first 6 months of life, presumably due to breastfeeding. Among the 654 children hospitalized for active HCMV infection, 379 (57.9%) were from rural areas and 275 (42.1%) from urban areas, showing that active infection in the countryside was higher than that in the city (χ2 = 32.65, p <0.01).


Assuntos
Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus/imunologia , Fatores Etários , Criança , Pré-Escolar , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Estudos Soroepidemiológicos , Fatores Socioeconômicos
13.
Chin J Integr Med ; 19(8): 621-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22610955

RESUMO

OBJECTIVE: To provide the distribution pattern and compatibility laws of the constituent herbs in prescriptions, for doctor's convenience to make decision in choosing correct herbs and prescriptions for treating respiratory disease. METHODS: Classical prescriptions treating respiratory disease were selected from authoritative prescription books. Data mining methods (frequent itemsets and association rules) were used to analyze the regular patterns and compatibility laws of the constituent herbs in the selected prescriptions. RESULTS: A total of 562 prescriptions were selected to be studied. The result exhibited that, Radix glycyrrhizae was the most frequently used in 47.2% prescriptions, other frequently used were Semen armeniacae amarum, Fructus schisandrae Chinese, Herba ephedrae, and Radix ginseng. Herbal ephedrae was always coupled with Semen armeniacae amarum with the confidence of 73.3%, and many herbs were always accompanied by Radix glycyrrhizae with high confidence. More over, Fructus schisandrae Chinese, Herba ephedrae and Rhizoma pinelliae was most commonly used to treat cough, dyspnoea and associated sputum respectively besides Radix glycyrrhizae and Semen armeniacae amarum. The prescriptions treating dyspnoea often used double herb group of Herba ephedrae & Radix glycyrrhizae, while prescriptions treating sputum often used double herb group of Rhizoma pinelliae & Radix glycyrrhizae and Rhizoma pinelliae & Semen armeniacae amarum, triple herb groups of Rhizoma pinelliae & Semen armeniacae amarum & Radix glycyrrhizae and Pericarpium citri reticulatae & Rhizoma pinelliae & Radix glycyrrhizae. CONCLUSIONS: The prescriptions treating respiratory disease showed common compatibility laws in using herbs and special compatibility laws for treating different respiratory symptoms. These principle patterns and special compatibility laws reported here could be useful for doctors to choose correct herbs and prescriptions in treating respiratory disease.


Assuntos
Mineração de Dados/métodos , Prescrições de Medicamentos/classificação , Medicamentos de Ervas Chinesas/classificação , Medicina Tradicional Chinesa/métodos , Doenças Respiratórias/tratamento farmacológico , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Interações Ervas-Drogas/fisiologia , Humanos , Doenças Respiratórias/epidemiologia , Literatura de Revisão como Assunto
14.
Anticancer Res ; 32(10): 4385-94, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23060563

RESUMO

BACKGROUND: Past work has established that human glioblastomas and breast cancer cells invariably express the activating transcription factor 5 (ATF5) and that loss of function of ATF5 caused massive apoptotic death of all cancer cell lines tested. ATF5 expression and function in pancreatic cancer cells have not been investigated. MATERIALS AND METHODS: Quantitative real-time/reverse transcription-polymerase chain reaction (QRT/RT-PCR), western blotting (WB), immunohistochemistry (IHC) and promoter reporter assay were used for gene expression analysis. MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS (fluorescence-activated cell sorting) analysis were used to monitor cell viability/apoptosis. RESULTS: ATF5 is highly expressed in pancreatic cancer cells as compared with non-tumor tissues. Both paclitaxel treatment and loss of function of ATF5 elicited apoptosis of SW1990 cells. Interference with ATF5 function in SW1990 cells resulted in down-regulation of BCL-2 and up-regulation of BAX, resulting in enhanced sensitivity to apoptosis induced by paclitaxel treatment. CONCLUSION: ATF5 is highly expressed in pancreatic cancer cells. Targeting ATF5 significantly enhances paclitaxel-induced apoptosis in human pancreatic cancer cells. ATF5 could be an important therapeutic target for pancreatic cancer treatment.


Assuntos
Fatores Ativadores da Transcrição/biossíntese , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Fatores Ativadores da Transcrição/antagonistas & inibidores , Adulto , Idoso , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/biossíntese
15.
Virol Sin ; 27(1): 19-25, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22270803

RESUMO

To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1(HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRb1, GRb1+HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRb1 on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 µg/mL GRb1 and 400 µg/mL GRb1+HSV-1 groups, MTT values were higher than control group at all times (P<0. 05). Moreover, the apoptosis rate in the 400 µg/mL GRb1+HSV-1 group was lower than the HSV-1 group (P<0. 05). These results confirmed that, at appropriate concentrations, GRb1 could inhibit nerve cell apoptosis in HSV-1 infections.


Assuntos
Apoptose , Ginsenosídeos/metabolismo , Herpesvirus Humano 1/patogenicidade , Neuroglia/efeitos dos fármacos , Neuroglia/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Coloração e Rotulagem/métodos , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo
16.
Biosci Biotechnol Biochem ; 74(7): 1368-72, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20622455

RESUMO

To develop a gene therapeutic method for human cytomegalovirus (HCMV), the IE86 specific short hairpin (sh) RNA expressing vector was constructed and subsequently transfected into MRC-5 cells. After infection of these cells with HCMV AD169, expression of IE86 was reduced strikingly as compared to the control. In addition, the inhibitory effect corresponded to a decrease in viral DNA replication and the virus-induced cytopathic effect. Measurement of the virus yield demonstrated that infection of cells expressing IE86-specific shRNA resulted in suppression of the formation of infectious viral progeny. These observations indicate that IE86 can be used as an effective target against HCMV infection using RNA interference (RNAi) technology, which provides new possibilities for anti-HCMV studies.


Assuntos
Infecções por Citomegalovirus/genética , Citomegalovirus/fisiologia , Proteínas Imediatamente Precoces/deficiência , Proteínas Imediatamente Precoces/genética , Sequências Repetidas Invertidas , Interferência de RNA , RNA Interferente Pequeno/genética , Transativadores/deficiência , Transativadores/genética , Linhagem Celular , Citomegalovirus/metabolismo , Efeito Citopatogênico Viral/genética , Replicação do DNA/genética , DNA Viral/biossíntese , Terapia Genética , Vetores Genéticos/genética , Humanos , RNA Mensageiro/genética , Transfecção , Replicação Viral/genética
17.
Protein Pept Lett ; 17(10): 1280-4, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20518734

RESUMO

In the current study, a mutant recombinant human interleukin-2 (MhIL-2) was generated using site-directed mutagenesis. The bacteria transformed with plasmid pET15b-MhIL-2 were cultured in LB medium containing 0.6mM IPTG for 8 hours at 27°C. Approximately 90% of His-MhIL-2 was efficiently expressed in soluble form. Purification efficiency was optimized using a number of strategies, including nickel ion chelating chromatography, desalting chromatography, thrombin cleavage and Superdex 75 gel filtration chromatography. The final product had >95% purity. PBMCs, CD4+ and CD8+ T cell proliferation assays revealed that one such mutant has identical functional property to the wild-type hIL-2. In summary, we generated a mutant hIL-2 that is functionally identical to wild-type hIL-2.


Assuntos
Interleucina-2 , Proteínas Recombinantes de Fusão , Western Blotting , Linfócitos T CD8-Positivos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Humanos , Interleucina-2/genética , Interleucina-2/isolamento & purificação , Interleucina-2/metabolismo , Interleucina-2/farmacologia , Mutagênese Sítio-Dirigida , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia
18.
Bing Du Xue Bao ; 26(6): 477-82, 2010 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-21344753

RESUMO

Nerve growth factor (NGF) is mainly secreted by the neuroglia cells, which can exert biological effect through its receptors on the specific target cell surface. NGF is closely related to neurocyte growth, differentiation and apoptosis. As a neurotropic virus, HSV-1 an easily lead to neurocyte, neuroglia cells death or apoptosis. In this study, the U251 human glioma cells were chosen as target cells to study the change of NGF and its receptors in the apoptosis process of HSV-1 infection. Our results showed that U251 cells were permissive to HSV-1 replication. In the apoptosis process of HSV-1 infected U251 cells, the expression of both NGF and P75NTR increased and then decreased, while the expression of TrkA decreased gradually. These result indicated that HSV-1 was able to induce the abnormal expression of NGF and its receptors in U251 cells.


Assuntos
Expressão Gênica , Glioma/genética , Herpes Simples/genética , Herpesvirus Humano 1/fisiologia , Fator de Crescimento Neural/genética , Receptor de Fator de Crescimento Neural/genética , Receptor trkA/genética , Apoptose , Linhagem Celular Tumoral , Glioma/metabolismo , Glioma/fisiopatologia , Glioma/virologia , Herpes Simples/metabolismo , Herpes Simples/fisiopatologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Humanos , Fator de Crescimento Neural/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Receptor trkA/metabolismo , Replicação Viral
19.
Biomed Environ Sci ; 22(4): 354-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19950533

RESUMO

OBJECTIVE: To explore the change of endogenic nerve growth factor (NGF) expression in human glioma cells infected with human cytomegalovirus (HCMV). METHODS: U251 cells were cultured in RPMI 1640 culture medium and infected with HCMV AD169 strain in vitro to establish a cell model of viral infection. Morphologic changes of U251 cells were observed under inverted microscope before and after infection with HCMV. Expression of NGF gene and protein of cells was detected by RT-PCR and Western blotting before and after infection with HCMV. RESULTS: The cytopathic effects of HCMV-infected cells appeared on day 5 after infection. However, differential NGF expression was evident on day 7. NGF expression was decreased significantly in U251 cells on day 7 after infection in comparison with control group (P < 0.05). CONCLUSION: HCMV can down-regulate endogenous NGF levels in human glioma cell line U251.


Assuntos
Infecções por Citomegalovirus/complicações , Citomegalovirus/fisiologia , Glioma/complicações , Glioma/virologia , Fator de Crescimento Neural/genética , Actinas/metabolismo , Linhagem Celular Tumoral , Infecções por Citomegalovirus/patologia , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Modelos Biológicos , Fator de Crescimento Neural/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Bing Du Xue Bao ; 25(3): 190-5, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-19634761

RESUMO

During the infection of host cells, IE2 protein is one of the first and most abundantly expressed products of HCMV genome, which plays an important role in the controlling of cell cycle and apoptosis. But the correlation between expression level and anti-apoptotic activity of IE2 protein is still not clear. In this study, we successfully established a HCMV IE2 protein expression cell line that was controlled by Tet-On system. The effect of IE2 protein on cell apoptosis and the expression of p53 was detected under different condition of induction. Our results showed that the IE2 protein could inhibit cell apoptosis induced by TNF-alpha. Additionally, the anti-apoptotic activity of IE2 protein seemed to be relevant to its expression level. However, we failed to detect any difference of p53 expression between the IE2 protein expression and non-expression cells. These data indicated that the IE2 protein might inhibit cell apoptosis through regulating different signal pathways.


Assuntos
Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Transativadores/genética , Transativadores/metabolismo , Antibacterianos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Doxiciclina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Células HeLa , Humanos , Plasmídeos/genética , Proteína Supressora de Tumor p53/metabolismo
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