RESUMO
Down syndrome cell adhesion molecule (DSCAM) is located within the Down syndrome critical region of chromosome 21. DSCAM is a broadly expressed neurodevelopmental protein involved in synaptogenesis, neurite outgrowth, and axon guidance. We previously demonstrated DSCAM overexpression in the cortex of amyloid precursor protein (APP) transgenic mice, suggesting possible regulatory interactions between APP and DSCAM. APP mice exhibit deficits in hippocampus-dependent learning and memory. In this preliminary study, we examined age-related changes in DSCAM expression within the hippocampus in 16 APP transgenic mice (1, 3, 6 and 12 months old). Hippocampus-dependent spatial memory was assessed in APP mice and age-matched wild type littermates (WTs) using the Morris water maze (MWM). The cellular distribution of hippocampal DSCAM and total expression at both mRNA and protein levels were measured by immunohistochemistry, qRT-PCR, and western blotting, respectively. APP mice exhibited spatial memory deficits in the MWM. Intense DSCAM immunoreactivity was observed in the dentate gyrus granule cell layer and hippocampal stratum pyramidale. Total hippocampal DSCAM mRNA and protein expression levels were substantially higher in APP mice than WTs at 1 and 3 months of age. Expression decreased with age in both groups but remained higher in APP mice. DSCAM is overexpressed in the hippocampus over the first 12 months of life in APP mice, but especially during maturation to adulthood. In conclusion, these results suggest an association between DSCAM and APP mice, which is characterized by neuropathology and behavioral deficits. These results provide some clues for future studies on the role of DSCAM overexpression in the precocious cognitive decline observed in APP transgenic mice.
Assuntos
Precursor de Proteína beta-Amiloide/genética , Moléculas de Adesão Celular/metabolismo , Hipocampo/metabolismo , Fatores Etários , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Síndrome de Down/metabolismo , Genótipo , Deficiências da Aprendizagem/metabolismo , Transtornos da Memória/metabolismo , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
We aimed to analyze gastric signet ring cell (SRC) carcinoma subtypes by investigating gastric and intestinal phenotypic marker expression, and explore the relationship between phenotype and K-ras mutation. Immunohistochemistry was performed on 163 SRC carcinoma patient specimens to detect gastric (MUC1, MUC5AC, and MUC6) and intestinal (MUC2 and CDX2) phenotypic markers, and tumors were classified into gastric (G), intestinal (I), and gastrointestinal (GI) phenotypes. DNA was extracted from the formalin-fixed, paraffin-embedded tumor samples, and K-ras mutations in codons 12, 13, and 61 were identified using polymerase chain reaction-based direct DNA sequencing. G, GI, and I phenotypes were observed in 63 (38.6%), 71 (43.5%), and 29 cases (17.8%), respectively. Expression of MUC2 was significantly associated with invasion depth and lymph node metastasis (P = 0.001 and 0.002, respectively), whereas that of CDX2 significantly corresponded to tumor size and submucosal invasion (P = 0.004 and 0.001, respectively). MUC5AC expression was inversely associated with gastric wall invasion (P = 0.001). Intestinal phenotypic marker expression was positively associated with gastric wall invasion and lymph node metastasis. K-ras mutations, all of which were in codon 12, were detected in 20 (12.27%) tumors, were significantly associated with the I phenotype, and exhibited an inverse relationship with MUC5AC and MUC6 expression. I-phenotype SRC carcinomas should be distinguished from those of the G phenotype because of their increased malignancy regarding invasion and metastasis, and higher K-ras aberration rate. The different K-ras mutation frequencies observed imply distinct genetic mechanisms in the carcinogenesis of I- and G-phenotype gastric SRC carcinomas.
Assuntos
Carcinoma de Células em Anel de Sinete/genética , Genes ras , Mutação , Fenótipo , Neoplasias Gástricas/genética , Biomarcadores Tumorais , Fator de Transcrição CDX2/genética , Fator de Transcrição CDX2/metabolismo , Carcinoma de Células em Anel de Sinete/classificação , Carcinoma de Células em Anel de Sinete/patologia , Códon/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/genética , Mucinas/metabolismo , Taxa de Mutação , Metástase Neoplásica , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologiaRESUMO
We investigate the relationship between IL-18 -607C/A and -137G/C genetic polymorphisms and development of acute pancreatitis in a Chinese population. A total of 153 patients were consecutively recruited from the First Affiliated Hospital of Chongqing Medical University between January 2013 and November 2014. Genotyping of IL-18 -607C/A and -137G/C variants was performed using the polymerase chain reaction-restriction fragment length polymorphism method. We observed a significant difference between acute pancreatitis patients and control subjects with respect to age (t = 2.15, P = 0.02), gender (chi-square = 3.95, P = 0.04), body mass index (t = 5.85, P < 0.001), and alcohol consumption (chi-square = 9.74, P = 0.002). Using chi-square tests, we found that the genotype distributions of IL-18 -607C/A (chi-square = 0.81, P = 0.67) and -137G/C (chi-square = 1.16, P = 0.56) polymorphisms did not differ between the acute pancreatitis and control groups. Genotype frequencies of these variants were consistent with Hardy-Weinberg equilibrium in both patient and control groups. In addition, logistic regression analysis failed to identify a significant association between these polymorphisms and acute pancreatitis risk. Our study firstly examined their association in a Chinese population, and we suggest that the IL-18 -607C/A and -137G/ C polymorphisms do not influence susceptibility to acute pancreatitis in the Chinese population studied in the present study.
Assuntos
Genótipo , Interleucina-18/genética , Pancreatite/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Doença Aguda , Fatores Etários , Idoso , Alelos , Povo Asiático , Índice de Massa Corporal , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Frequência do Gene , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/etnologia , Pancreatite/patologia , Fatores SexuaisRESUMO
In this study, a software tool (IFGFA) for identification of featured genes from gene expression data based on latent factor analysis was developed. Despite the availability of computational methods and statistical models appropriate for analyzing special genomic data, IFGFA provides a platform for predicting colon cancer-related genes and can be applied to other cancer types. The computational framework behind IFGFA is based on the well-established Bayesian factor and regression model and prior knowledge about the gene from OMIM. We validated the predicted genes by analyzing somatic mutations in patients. An interface was developed to enable users to run the computational framework efficiently through visual programming. IFGFA is executable in a Windows system and does not require other dependent software packages. This program can be freely downloaded at http://www.fupage.org/downloads/ifgfa.zip.
Assuntos
Análise Fatorial , Perfilação da Expressão Gênica/métodos , Software , Algoritmos , Teorema de Bayes , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Biologia Computacional/métodos , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência de DNA/métodos , TranscriptomaRESUMO
Sex hormones play important roles in breast cancer (BC) development. This study investigated associations between BC risk and hormone-related gene variants in Chinese women. In a cohort of 336 patients with histopathologically confirmed BC and 390 age-matched controls, we genotyped seven single nucleotide polymorphisms (SNPs) in five hormone-related genes: estrogen receptor-α (ESR1), aromatase (CYP19), catechol-O-methyl transferase (COMT), sex hormone-binding globulin (SHBG), and glutathione S-transferase (GSTP1). Among these seven SNPs, the SNPs in GSTP1 rs1695 [A/G; odds ratio (OR): 1.68; 95% confidence interval (CI): 1.23-2.30] and ESR1 rs2046210 (C/T; OR: 1.39; 95%CI = 1.02-1.91) were associated with an increased risk among heterozygote carriers. Homozygotes of minor alleles of CYP19 rs10046 (CC) were associated with a reduced risk of BC with OR: 0.61 (95%CI = 0.39-0.95). In addition, a stratified analysis by menopausal status indicated that the association of the CYP19 polymorphisms (rs10046 and rs700519) with BC risk was mainly evident in premenopausal women, and the association of CYP19 rs700519 with BC risk was significant in women less than 50 years old. Haplotype analysis identified 15 common haplotypes (>1%). The haplotype TGGGGTC was significantly associated with BC risk compared with the reference haplotype CGAGGTC (OR > 1000, P < 0.0001). Our data demonstrate that these ESR1, GSTP1, and CYP19 polymorphisms are associated with risk of BC, and the risk haplotype TGGGGTC could help to identify populations with high susceptibility to BC in Chinese women.
Assuntos
Aromatase/genética , Neoplasias da Mama/genética , Catecol O-Metiltransferase/genética , Receptor alfa de Estrogênio/genética , Glutationa S-Transferase pi/genética , Globulina de Ligação a Hormônio Sexual/genética , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.
Assuntos
Humanos , Caderinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/diagnóstico , Intervalos de Confiança , Metástase Linfática , Invasividade Neoplásica , Prognóstico , Análise de Regressão , Taxa de Sobrevida , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with intestinal-type GC. Moreover, the tumor depth of invasion differed significantly between patients with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were no significant differences between CDH17+ and CDH17- GC patients with respect to tumor node metastasis clinical stages, histological grades, or lymph node metastasis. Despite the differences in invasive depth, there was no significant difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our meta-analysis provides evidence that CDH17 protein expression may be associated with the development of GC, suggesting that CDH17 is an important biomarker that could be useful for the early diagnosis of GC. However, CDH17 levels do not appear to impact overall survival.
Assuntos
Caderinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/diagnóstico , Intervalos de Confiança , Humanos , Metástase Linfática , Invasividade Neoplásica , Prognóstico , Análise de Regressão , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
The aim of this study was to observe the effects of re-combinant human endostatin on the proliferation and apoptosis of mouse gastric cancer cells, and explore some possible mechanisms of recom-binant human endostatin inhibition of cancer. A murine gastric cancer xenograft model was established. A total of 20 mice were divided into two groups (control and experimental groups). The expression of c-Myc and basic fibroblast growth factor (bFGF) was determined by reverse transcription-polymerase chain reaction, Western blotting, and immu-nohistochemical staining methods. Tumor volume was measured and a growth curve was calculated. The tumor diameter in the experimental group was significantly smaller than that in the control group after treat-ment with endostatin for 21 days. The expression levels of c-Myc and bFGF in the experimental group were significantly lower than those of the control group (P < 0.05). There was a positive correlation between the expression of c-Myc and bFGF in the experimental group. Microvessel density was significantly inhibited in the experimental group (P < 0.05). These results demonstrated that recombinant human endostatin could in-hibit tumor metastasis by inhibition of the expression of c-Myc and bFGF in gastric cancer tissue as well as by inhibition of angiogenesis.
Assuntos
Endostatinas/administração & dosagem , Fator 2 de Crescimento de Fibroblastos/biossíntese , Neovascularização Patológica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-myc/biossíntese , Proteínas Recombinantes/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Endostatinas/genética , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Proteínas Proto-Oncogênicas c-myc/genética , RNA Mensageiro/biossíntese , Proteínas Recombinantes/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This study investigated the curative and toxic effects of three-dimensional conformal radiotherapy (3D-CRT), using repeated CT scans for field reduction in older non-small-cell lung cancer (NSCLC) patients. 3D-CRT was administered to 36 older patients with NSCLC, and irradiation fields included the primary lesion and metastatic lymph nodes. After CT localization scanning, images were fed into a treatment planning system to delineate the gross tumor volume (GTV)1 and prepare Plan 1. After the DT50 (dose of the tumor is 50 Gy) increased from 50 Gy in 25 fractions to 54 Gy in 27 fractions, secondary CT localization scanning was performed to delineate GTV2 and prepare Plan 2; radiotherapy was administered continuously. When the DT increased to 60-65 Gy, tertiary CT scanning was performed to prepare another plan. The field was reduced to boost irradiation to the residual target volume until the total DT increased to 68-74 Gy. Compared with GTV1, the median absolute volume regression and median relative regression amounts for GTV2 were 68.85 cm(3) and 31.17%, respectively (Z = -2.673, P = 0.021). There were 8 cases of complete remission (22.2%), 20 of partial remission (55.6%), 7 of stable disease (19.4%), and 1 of progressive disease (2.8%). The total effectiveness rate was 77.8% and the 1- and 2-year survival rates were 63.9 and 27.8%, respectively. Radiation esophagitis and radiation pneumonia, the main toxic side effects, were tolerable. 3D-CRT, using repeated CT scans for field reduction in older NSCLC patients, could increase the local control and survival rates and relieve the toxic radiotherapy side effects.
Assuntos
Adenocarcinoma/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Raios gama/uso terapêutico , Neoplasias Pulmonares/radioterapia , Radioterapia Conformacional/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Relação Dose-Resposta à Radiação , Esofagite/etiologia , Esofagite/mortalidade , Esofagite/patologia , Feminino , Raios gama/efeitos adversos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/mortalidade , Pneumonite por Radiação/patologia , Radiometria , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Carga Tumoral/efeitos da radiaçãoRESUMO
The association of the single nucleotide polymorphism 301T>C in the coding region of the acylation-stimulating protein (ASP) gene with coronary heart disease (CHD) was investigated in the Uygur (385 CHD patients and 483 control subjects) and Han (390 CHD patients and 439 control subjects) populations of China. The frequency of the CC and CT genotypes was significantly higher in patients with CHD compared to the control group (55.3 vs 46.2%, P = 0.001) in the Uygur population, but in the Han population, the frequency was significantly higher in the control group (51.7 vs 24.4%, P < 0.001). In addition, the C allele was significantly associated with CHD in the Uygur population (C allele: 33.8 vs 26.2%, T allele: 66.2 vs 73.8%; P = 0.004) and in the Han population (C allele: 14.5 vs 30.3%, T allele: 85.5 vs 69.7%; P < 0.001). The CC genotype was independently associated with increased risk of coronary artery disease when adjusted for other cardiovascular risk factors [odds ratio (OR) = 2.189, 95% confidence interval (CI) = 1.251-3.830, P = 0.001] in the Uygur population, but was a protective factor for CHD in the Han population (OR = 0.373, 95%CI = 0.187-0.745, P = 0.005). In conclusion, the 301T>C polymorphism of the ASP gene that influences the serum triglycerides level in the Uygur population, is associated with the development of CHD, and the CC genotype might be a risk factor of CHD.
Assuntos
Complemento C3a/genética , Doença das Coronárias/genética , Predisposição Genética para Doença , Triglicerídeos/sangue , Acilação/genética , Idoso , Povo Asiático/genética , China , Doença das Coronárias/sangue , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Cauda equina syndrome (CES) is characterized by varying patterns of low back pain, sciatica, lower extremity sensorimotor loss, and bowel and bladder dysfunction. The prognosis for complete recovery of CES is dependent on not only the time before surgical intervention with decompression but also the severity of the nerve damage. Delayed or severe nerve compression impairs the capability of nerve regeneration. Transplantation of neural stem cells (NSCs) may facilitate axon regeneration and functional recovery in a spectrum of neurological disorders. Our study shows that the NSCs derived from early postnatal dorsal root ganglion (DRG) are able to proliferate to form neurospheres and differentiate into O4(+) oligodendrocytes but not glial fibrillary acidic protein (GFAP(+)) astrocytes or ßIII-tubulin(+) neurons in vitro. After intrathecal transplantation into the lumbar spinal canal stenosis animal model, most of the GFP-expressing NSCs were induced to differentiate into oligodendrocytes in vivo. Although the recovery of sensorimotor function was not significantly improved in rats with transplantation therapy, our results implied that subarachnoid microinjection of NSCs may promote axon regeneration of DRG neurons in the cauda equina model after nerve injury.
Assuntos
Diferenciação Celular , Gânglios Espinais/patologia , Células-Tronco Neurais/fisiologia , Oligodendroglia/metabolismo , Polirradiculopatia/terapia , Animais , Cauda Equina/patologia , Cauda Equina/fisiopatologia , Células Cultivadas , Masculino , Regeneração Nervosa , Células-Tronco Neurais/transplante , Nociceptividade , Polirradiculopatia/fisiopatologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Esferoides Celulares/metabolismoRESUMO
This study was designed to estimate the prevalence of diabetes and impaired fasting glucose (IFG) in Xinjiang children in western China. Data were obtained from the Chun-Miao Project, a community-based, cross-sectional study designed to investigate the prevalence and risk factors of diabetes in children of the Chinese Uygur population in Xinjiang from February 2010 to May 2012. A total of 3644 children completed the survey and measurements of fasting glucose. Diabetes and IFG were defined using American Diabetes Association 2009 criteria. Overall, 0.7% of the 3644 Uygur children had IFG and 0.1% had diabetes. In the newborn to 8-year-old group, the prevalence of diabetes and IFG was 0.6 and 1.1%, respectively. In the 9-13-year-old group, the prevalence of diabetes and IFG was 0.1 and 0.7%, respectively. There was no evidence of IFG or diabetes in the 14-17-year-old group. Logistic regression analysis suggested that overweight and obesity were independent risk factors of diabetes in Uygur children of Xinjiang. The prevalence of diabetes and IFG in Uygur children was lower than that reported previously in children of other ethnicities in China.
Assuntos
Glicemia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , China/etnologia , Estudos Transversais , Etnicidade , Jejum , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Vigilância em Saúde Pública , Fatores de RiscoRESUMO
Single nucleotide polymorphism (SNP)-based genome-wide association studies have revealed that polymorphisms of the ORM1-like 3 (ORMDL3) gene are associated with childhood asthma. We investigated genetic associations of SNPs in and around the ORMDL3 gene with childhood asthma in a Chinese population. Genomic DNA was extracted from peripheral venous blood drawn from 152 subjects with childhood asthma and from 190 control subjects. SNP genotyping was performed with the MassARRAY system (Sequenom) by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among the six SNPs, only the genotype frequencies of rs7216389 were significantly different between asthmatic children and controls. Asthmatic children had a significantly higher frequency of T alleles [odds ratio (OR) = 1.653, 95% confidence interval (95%CI) = 1.170-2.333] in rs7216389, than controls. The TT genotype of rs7216389 was found to be a significant risk factor for childhood asthma by logistic regression analysis (OR = 1.704, 95%CI = 1.105-2.628). There was no significant association between the TT genotype of rs7216389 and clinical features of childhood asthma. We conclude that the ORMDL3 gene influences childhood asthma and that the TT genotype of the rs7216389 polymorphism is associated with childhood asthma in the Chinese population.
Assuntos
Asma/genética , Povo Asiático , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Proteínas de Membrana , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Análise de Sequência de DNARESUMO
C5L2, a G protein-coupled receptor, is known to be a functional receptor of acylation-stimulating protein, which is a stimulator of triglyceride synthesis and glucose transport. A novel C5L2 variant (S323I) was identified and its association with familial combined hyperlipidemia (FCH) was recently reported. We looked for this SNP in three Chinese ethnic groups, including Han, Uygur, and Kazakh controls and patients with FCH and type 2 diabetes. One hundred and eighty-two unrelated subjects (77 of Han, 57 of Uygur, and 48 of Kazakh) with FCH were genotyped by direct sequencing, and 852 subjects (342 of Han, 338 of Uygur, 172 of Kazakh) with type 2 diabetes and 200 healthy controls (67 of Han, 72 of Uygur, and 61 of Kazakh) chosen from a cardiovascular risk survey study were genotyped with PCR-RFLP analysis. All 182 subjects with FCH, 99.5% of the type 2 diabetes patients and 100% of the healthy controls were successfully genotyped. Neither the FCH subjects nor the type 2 diabetes patients were found to have the S323I variant. This variant was also not identified in the healthy controls. We found no evidence to demonstrate that the S323I polymorphism contributes to familial combined hyperlipidemia or type 2 diabetes in the Chinese population.
Assuntos
Povo Asiático , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Hiperlipidemia Familiar Combinada/genética , Polimorfismo de Nucleotídeo Único , Receptores de Quimiocinas/genética , Adulto , Idoso , Alelos , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , China/epidemiologia , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Hiperlipidemia Familiar Combinada/complicações , Hiperlipidemia Familiar Combinada/etnologia , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Receptor da Anafilatoxina C5a , Fatores de Risco , Serina/genéticaRESUMO
Lipopolysaccharide exerts many effects on many cell lines, including cytokine secretion, and cell apoptosis and necrosis. We investigated the in vitro effects of lipopolysaccharide on apoptosis of cultured human dental pulp cells and the expression of Bcl-2 and Bax. Dental pulp cells showed morphologies typical of apoptosis after exposure to lipopolysaccharide. Flow cytometry showed that the rate of apoptosis of human dental pulp cells increased with increasing lipopolysaccharide concentration. Compared with controls, lipopolysaccharide promoted pulp cell apoptosis (P < 0.05) from 0.1 to 100 μg/mL but not at 0.01 μg/mL. Cell apoptosis was statistically higher after exposure to lipopolysaccharide for 3 days compared with 1 day, but no difference was observed between 3 and 5 days. Immunohistochemistry showed that expression of Bax and Bcl-2 was enhanced by lipopolysaccharide at high concentrations, but no evident expression was observed at low concentrations (0.01 and 0.1 μg/mL) or in the control groups. In conclusion, lipopolysaccharide induced dental pulp cell apoptosis in a dose-dependent manner, but apoptosis did not increase with treatment duration. The expression of the apoptosis regulatory proteins Bax and Bcl-2 was also up-regulated in pulp cells after exposure to a high concentration of lipopolysaccharide.
Assuntos
Adulto , Humanos , Adulto Jovem , Apoptose , Polpa Dentária/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , /metabolismo , /metabolismo , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Citometria de Fluxo , Imuno-Histoquímica , Fatores de TempoRESUMO
Lipopolysaccharide exerts many effects on many cell lines, including cytokine secretion, and cell apoptosis and necrosis. We investigated the in vitro effects of lipopolysaccharide on apoptosis of cultured human dental pulp cells and the expression of Bcl-2 and Bax. Dental pulp cells showed morphologies typical of apoptosis after exposure to lipopolysaccharide. Flow cytometry showed that the rate of apoptosis of human dental pulp cells increased with increasing lipopolysaccharide concentration. Compared with controls, lipopolysaccharide promoted pulp cell apoptosis (P < 0.05) from 0.1 to 100 µg/mL but not at 0.01 µg/mL. Cell apoptosis was statistically higher after exposure to lipopolysaccharide for 3 days compared with 1 day, but no difference was observed between 3 and 5 days. Immunohistochemistry showed that expression of Bax and Bcl-2 was enhanced by lipopolysaccharide at high concentrations, but no evident expression was observed at low concentrations (0.01 and 0.1 µg/mL) or in the control groups. In conclusion, lipopolysaccharide induced dental pulp cell apoptosis in a dose-dependent manner, but apoptosis did not increase with treatment duration. The expression of the apoptosis regulatory proteins Bax and Bcl-2 was also up-regulated in pulp cells after exposure to a high concentration of lipopolysaccharide.