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1.
Cell Transplant ; 29: 963689720912690, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32193954

RESUMO

Breastfeeding has been shown to have a protective effect on the occurrence of necrotizing enterocolitis (NEC), but the mechanism remains unclear. In the context of NEC pathogenesis, many of the protective properties of exosomes on the intestinal epithelial compartment make it an ideal therapeutic target. In the present study, our hypothesis was that intestinal stem cells (ISCs) would be protected from injury by human milk-derived exosomes (HMDEs). Human breast milk was collected, and exosomes were isolated using ExoQuick reagent. Magnetic-activated cell sorting isolation of prominin-1+ ISCs was performed from small intestines of neonatal rat. ISCs were treated with or without H2O2, and HMDEs, an equal volume of HMDE-free milk, or a control solution [phosphate-buffered solution (PBS)] was added, respectively. In the absence of HMDEs, exposure of ISCs to H2O2 led to decreased cell viability. However, addition of HMDEs to ISCs exposed to H2O2 led to significantly increased ISC viability. There was a significant upregulation of mRNA expression of Axin2, c-Myc, and Cyclin D1 genes of the Wnt/ß-catenin axis in ISCs treated with HMDEs (6.99 ± 2.34, 4.21 ± 1.68, 6.17 ± 2.22, respectively, P < 0.05 for all), as compared to control. In the presence of carnosic acid (a specific Wnt/ß-catenin signaling inhibitor), the cell viability was significantly decreased. Thus, HMDEs protect ISCs from oxidative stress injury in vitro, which were possibly mediated via the Wnt/ß-catenin signaling pathway. Our findings indicate that oral administration of HMDEs might be a promising measure in treating NEC or in preventing the development of NEC in high-risk infants when breast milk is not available.

2.
Proteomics ; 16(1): 12-28, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26435169

RESUMO

Menopause is one of the crucial physiological events during the life of a woman. Transition of menopause status is accompanied by increased risks of various health problems such as osteoporosis. Peripheral blood monocytes can differentiate into osteoclasts and produce cytokines important for osteoclast activity. With quantitative proteomics LC-nano-ESI-MS(E) (where MS(E) is elevated-energy MS), we performed protein expression profiling of peripheral blood monocytes in 42 postmenopausal women with discordant bone mineral density (BMD) levels. Traditional comparative analysis showed proteins encoded by four genes (LOC654188, PPIA, TAGLN2, YWHAB) and three genes (LMNB1, ANXA2P2, ANXA2) were significantly down- and upregulated, respectively, in extremely low- versus high-BMD subjects. To study functionally orchestrating groups of detected proteins in the form of networks, we performed weighted gene coexpression network analysis and gene set enrichment analysis. Weighted gene coexpression network analysis showed that the module including the annexin gene family was most significantly correlated with low BMD, and the lipid-binding related GO terms were enriched in this identified module. Gene set enrichment analysis revealed that two significantly enriched gene sets may be involved in postmenopausal BMD variation by regulating pro-inflammatory cytokines activities. To gain more insights into the proteomics data generated, we performed integrative analyses of the datasets available to us at the genome (DNA level), transcriptome (RNA level), and proteome levels jointly.


Assuntos
Redes Reguladoras de Genes , Leucócitos Mononucleares/patologia , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/patologia , Proteínas/genética , Proteômica/métodos , Idoso , Anexinas/genética , Anexinas/metabolismo , Densidade Óssea , Proteína de Capeamento de Actina CapZ/genética , Proteína de Capeamento de Actina CapZ/metabolismo , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/metabolismo , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas , Proteínas/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Transcriptoma , Ubiquitina/genética , Ubiquitina/metabolismo
3.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(9): 2544-7, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26669164

RESUMO

As a common spectral characterization technique, Raman spectroscopy is widely used and has a specified calibration procedure. Based on laser confocal micro-Raman spectrometer, in this paper, we briefly introduced the principle, configuration and main components of Raman spectrometer. In addition, the calibration procedures were also presented, with an emphasis on the calibration of spectrometer (spectrograph) and that of excitation laser wavelength. On the basis of conventional calibration method, a novel and more accurate method was proposed to obtain the actual excitation wavelength, that is, calibration at the point of Raman shift Δν=0. Using this novel calibration method of excitation wavelength, Raman frequency shift values of sulfur were measured, and compared with the standard values from American Society Testing and Materials (ASTM). As a result, the measured values after calibration were consistent with those ASTM values, which indicated that the calibration method is accurate. Thus, a more reasonable calibration procedure of the laser confocal micro-Raman spectrometer was provided.

4.
Neurologist ; 20(2): 23-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26280286

RESUMO

BACKGROUND AND PURPOSE: Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (eGFR) and carotid plaques, stenosis and occlusions, and to assess whether CKD and its severity affect carotid atherosclerosis in a cohort of unselected patients with acute stroke. METHODS: A total of 249 consecutive patients with acute stroke (ischemic or hemorrhagic) were included in this study and baseline eGFR, carotid intima-media thickness (cIMT), and carotid stenosis were evaluated. The eGFR was calculated using the modified Modification of Diet in Renal Disease equation, which was adjusted for data from Chinese CKD patients. An eGFR rate of <60 mL/min/1.73 m was defined as CKD. The cIMT and carotid plaques were detected by carotid ultrasound. RESULTS: CKD, defined as eGFR<60 mL/min/1.73 m, was found in 66 individuals (26.50%). Among the 5 subtypes, the level of low-density lipoprotein cholesterol was significantly higher in the moderate and severe stenosis groups compared with the normal, elevated cIMT and mild stenosis groups (P<0.01). The value of eGFR gradually decreased with increasing degree of carotid stenosis, and the differences between the groups were statistically significant (P<0.01). On linear regression analysis, eGFR was negatively correlated with the degree of carotid stenosis (r=0.03; P<0.05). On ordinal logistic regression analysis, eGFR was an independent risk factor associated with carotid atherosclerosis (1.05; 95% confidence interval, 0.47-1.63). CONCLUSIONS: There was a significant burden of atherosclerosis among individuals with CKD. CKD is an independent predictor of carotid plaques, stenoses, and occlusions in patients with acute stroke.


Assuntos
Doenças das Artérias Carótidas/etiologia , Insuficiência Renal Crônica/etiologia , Acidente Vascular Cerebral/complicações , Idoso , Doenças das Artérias Carótidas/diagnóstico , Espessura Intima-Media Carotídea , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler
5.
Mol Med Rep ; 11(5): 3511-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25572489

RESUMO

The present study aimed to evaluate whether the ­A930G polymorphism of the nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase p22phox gene is involved in intracerebral hemorrhage (ICH) in the Chinese Han population. In the present case­control investigation, the subjects included 118 patients with ICH and 147 healthy controls. The ­A930G polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. Furthermore, the correlation between the ­A930G gene polymorphism and ICH was evaluated using statistical analyses. The distribution of p22phox ­A930G genotypes differed significantly between the two groups (P=0.003), with the AA, AG and GG genotype frequencies being 61.9, 29.3 and 8.8% in the control group and 40.7, 45.8 and 13.6% in the ICH group, respectively. The G allele frequency was significantly higher in patients with ICH compared with healthy controls (36.4 vs. 23.5%; P<0.05), however, the opposite was observed in the frequency of the A allele (63.6 vs. 76.5%; P<0.05). Binary logistic regression analysis revealed that genetic mutations of the p22phox ­A930G gene were independent risk factors of ICH (odds ratio, 2.196; 95% confidence interval, 1.003­4.586; P=0.009). In addition, certain conventional factors were associated with increased risk of ICH, including elevated blood pressure, increased levels of glucose and triglycerides in the blood, a history of hypertension and smoking. The ­A930G polymorphism of the p22phox gene may affect the susceptibility to ICH and certain haplotypes of the gene may be associated with a higher susceptibility to ICH.


Assuntos
Hemorragia Cerebral/genética , Estudos de Associação Genética , Predisposição Genética para Doença , NADPH Oxidases/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Estudos de Casos e Controles , Hemorragia Cerebral/metabolismo , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sequência de DNA
6.
Pharmacology ; 94(3-4): 115-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247335

RESUMO

BACKGROUND: Genome-wide association studies identified that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) genetic polymorphisms are related to type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and pioglitazone efficacy in Chinese T2DM patients. METHODS: A total of 281 T2DM patients and 111 healthy volunteers were enrolled to identify the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms; 86 patients were randomly selected and given a 12-week pioglitazone treatment (30 mg/day). Fasting plasma glucose, postprandial plasma glucose (PPG), glycated hemoglobin, serum triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-C) were determined before and after pioglitazone treatment. RESULTS: The results showed that the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM in a Chinese population (OR = 2.002, 95% CI 1.170-3.426, p < 0.05; OR = 1.879, 95% CI 1.110-3.182, p < 0.05). The effect of pioglitazone on PPG (p < 0.05), TG (p < 0.01) and HDL-C (p < 0.05) was lower in patients with the rs1470579 AC+CC genotypes than in AA genotype carriers. Its effect on PPG level was also lower in patients with the GT+TT genotypes of rs4402960 than in patients with the GG genotype (p < 0.05). CONCLUSIONS: The IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and therapeutic efficacy of pioglitazone in this Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Hipoglicemiantes/uso terapêutico , Proteínas de Ligação a RNA/genética , Tiazolidinedionas/uso terapêutico , Glicemia/análise , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Pioglitazona , Polimorfismo Genético , Tiazolidinedionas/farmacologia , Triglicerídeos/sangue
7.
N Engl J Med ; 370(13): 1220-6, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24670168

RESUMO

The human zona pellucida is composed of four glycoproteins (ZP1, ZP2, ZP3, and ZP4) and has an important role in reproduction. Here we describe a form of infertility with an autosomal recessive mode of inheritance, characterized by abnormal eggs that lack a zona pellucida. We identified a homozygous frameshift mutation in ZP1 in six family members. In vitro studies showed that defective ZP1 proteins and normal ZP3 proteins colocalized throughout the cells and were not expressed at the cell surface, suggesting that the aberrant ZP1 results in the sequestration of ZP3 in the cytoplasm, thereby preventing the formation of the zona pellucida around the oocyte.


Assuntos
Proteínas do Ovo/genética , Proteínas do Ovo/metabolismo , Genes Recessivos , Infertilidade Feminina/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Óvulo/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Adulto , China , Análise Mutacional de DNA , Proteínas do Ovo/química , Feminino , Mutação da Fase de Leitura , Heterozigoto , Homozigoto , Humanos , Infertilidade Feminina/patologia , Glicoproteínas de Membrana/química , Óvulo/patologia , Linhagem , Receptores de Superfície Celular/química , Glicoproteínas da Zona Pelúcida
8.
J Stroke Cerebrovasc Dis ; 23(6): 1275-81, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24462462

RESUMO

BACKGROUND: To investigate the relationship between the HindIII polymorphism and hypertensive intracerebral hemorrhage (HIH) and lipid metabolism. METHODS: A polymerase chain reaction-restriction fragment length polymorphism assay and the chain termination DNA sequencing method were used to determine the HindIII genotypes of 267 subjects, which included 120 cerebral hemorrhagic patients and 147 controls. The fasting levels of lipids and glucose in the plasma were used to measure the effect of genotype on HIH risk factors. RESULTS: The frequency of the T allele of the HindIII polymorphism in the HIH group was 90.8%. The frequency of the G allele was 9.2%. In the control group, the frequencies were 82.3% T and 17.7% G, which indicated that the proportion of the G allele in the HIH patient group was significantly lower than in the control group (P<.05). The frequency of GG+GT genotypes in HIH patients (P<.05) and the plasma triglyceride (TG) levels in these patients (P<.05) were also lower than in the control group. The levels of plasma TG, low-density lipoprotein cholesterol, glucose, systolic blood pressure, and diastolic blood pressure in the HIH group were higher than in the controls (P<.05). After controlling for risk factors related to HIH, the HindIII G allele was negatively correlated with the incidence of HIH (odds ratio=.417, 95% confidence interval: .193-.901). CONCLUSIONS: The HindIII G allele may be a protective factor against the development of HIH among the Han Chinese population.


Assuntos
Predisposição Genética para Doença , Hemorragia Intracraniana Hipertensiva/genética , Lipase Lipoproteica/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Grupo com Ancestrais do Continente Asiático/genética , Glicemia , China , HDL-Colesterol/sangue , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Hemorragia Intracraniana Hipertensiva/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
9.
Mol Med Rep ; 9(2): 614-20, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24317109

RESUMO

The second mitochondria­derived activator of caspases (Smac), an antagonist of the inhibitor of apoptosis protein (IAP), increases chemosensitivity in vitro. Survivin, an IAP family member, mediates cancer cell survival and chemoresistance. The present study investigated the correlation between Smac and survivin expression in primary breast cancer, and the sensitivity to anthracycline during neoadjuvant chemotherapy (NAC). Pre­treatment biopsies and post­anthracycline treatment tumor sections were analyzed from 98 cases. Biomarker expression was evaluated by immunohistochemistry in tumor samples from clinical stage II and III anthracycline­based NAC­treated breast cancer. A univariate analysis indicated that the estrogen receptor (ER), Smac and survivin were significantly predictive of a pathological complete response (pCR) (P=0.004, 0.001 and 0.037, respectively) in pre­chemotherapy samples. ER, Smac and survivin expression was also significant for pCR on the multivariate analysis (P=0.001, 0.031 and 0.012, respectively). An inverse association was identified between survivin and Smac expression (r=­0.217, P=0.032; and r=­0.335, P=0.003, respectively) prior to and following NAC. The patients with low survivin expression or high Smac expression had significantly longer disease­free survival (DFS; P=0.012 and P=0.020, respectively) and overall survival (OS; P=0.01 and P=0.033, respectively) compared with the patients with high survivin or low Smac expression. Cox regression analyses demonstrated that survivin, Smac and clinical stage were independent predictors for DFS and OS. The present study indicated the significance of Smac and survivin in determining the breast cancer response to anthracycline­based chemotherapy, and may permit further stratifying of pre­chemotherapy patients to undertake more tailored treatments.


Assuntos
Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas Inibidoras de Apoptose/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas Mitocondriais/biossíntese , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proteínas Reguladoras de Apoptose , Biópsia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Receptores Estrogênicos/genética , Survivina
10.
Clin Chem Lab Med ; 51(9): 1755-60, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23729572

RESUMO

BACKGROUND: ß3-Adrenergic receptor (ß3-AR) gene is associated with insulin resistance and may affect serum uric acid levels. Our aim was to determine the possible association between ß3-AR gene Trp64Arg polymorphism (rs4994) and hyperuricemia in a Chinese male population. METHODS: A total of 410 hyperuricemic and 420 normouricemic male subjects were genotyped in this study. The genotypic and allelic frequencies were compared between the two groups. Body mass index (BMI), waist to hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum uric acid, urea nitrogen, creatinine, triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and fasting plasma glucose (FPG) were determined. RESULTS: The frequencies of CC genotype and C allele for Trp64Arg polymorphism were higher in hyperuricemic group than in normouricemic group (p<0.01 and p<0.05, respectively). In both hyperuricemic and normouricemic groups, subjects with mutated C allele of Trp64Arg polymorphism showed significantly higher average uric acid levels than TT genotype carriers (p<0.01 and p<0.01, respectively). Univariate and multivariate logistic regression showed that carrier of mutated C allele of Trp64Arg polymorphism was significantly associated with hyperuricemia occurrence (p=0.003, OR=1.587, 95% CI 1.175-2.145 and p=0.003, OR=1.676, 95% CI 1.051-3.617). CONCLUSIONS: Trp64Arg polymorphism was associated with hyperuricemia in a Chinese male population and should be an independent risk factor for hyperuricemia.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hiperuricemia/genética , Receptores Adrenérgicos beta 3/genética , Adulto , Idoso , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Hiperuricemia/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Ácido Úrico/sangue , Adulto Jovem
11.
Acta Pharmacol Sin ; 34(2): 255-61, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23147557

RESUMO

AIM: To investigate the influence of peroxisome proliferator-activated receptor γ2 (PPAR-γ2) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population. METHODS: One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled. Among them, 67 type 2 diabetes patients were administered pioglitazone (30 mg/d, po) for 3 months. All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry. Fasting plasma glucose, postprandial plasma glucose, glycated hemoglobin, serum triglyceride, total cholesterol, low-density and high-density lipoprotein-cholesterol were determined. RESULTS: The PPAR-γ2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility (OR=0.515, 95% CI 0.268-0.990) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes (OR=1.984, 95% CI 1.135-3.469) in a dominant model adjusted for age, gender and BMI. After pioglitazone treatment for 3 months, the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postprandial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype. The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with rs17584499 CC genotype. CONCLUSION: Diabetes risk alleles in PPAR-γ2 (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic efficacy.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Hipoglicemiantes/uso terapêutico , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Tiazolidinedionas/uso terapêutico , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pioglitazona
12.
Acta Pharmacol Sin ; 33(12): 1563-70, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23085740

RESUMO

AIM: To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients. METHODS: One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clinical indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4*1G, CYP3A5*3C, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T polymorphisms. Whole blood trough concentrations of CsA at time zero (C(0)) were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted C(0) (C(0)/dose) based on several clinical indices. RESULTS: The CYP3A5*3C polymorphism influenced the C(0) and C(0)/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs (CYP3A4*1G, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T). In a univariate analysis using Pearson's correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA C(0)/dose. In the multiple regression model, CYP3A5*3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA C(0)/dose. CONCLUSION: CYP3A5*3C correlates with the C(0)/dose of CsA on the seventh day after renal transplantation. The allele is a putative indicator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Grupo com Ancestrais do Continente Asiático/genética , Ciclosporina/farmacocinética , Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Transplante de Rim , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adolescente , Adulto , China , Ciclosporina/sangue , Feminino , Haplótipos , Humanos , Imunossupressores/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
Asian Pac J Cancer Prev ; 13(8): 3917-25, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23098493

RESUMO

BACKGROUND: The relationship between postmenopausal hormone therapy (HT) and invasive breast cancer has been extensively investigated, but that with breast carcinoma in situ (BCIS) has received relatively little attention. The aim of our present study was to review and summarize the evidence provided by longitudinal studies on the association between postmenopausal HT use and BCIS risk. METHODS: A comprehensive literature search for articles published up to May 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risk (RR) or odds ratio (OR) values were calculated using 14 reports (8 case-control studies and 6 cohort studies), published between 1986 and 2012. RESULTS: There was evidence of an association between ever postmenopausal estrogen use and BCIS based on a random-effects model (RR = 1.25, 95% confidence interval (CI) = 1.01, 1.55). However, we found no strong evidence of an association between ever postmenopausal estrogen combined with progesterone use and BCIS using a random- effects model (RR = 1.55, 95% CI = 0.95, 2.51). Furthermore, our analysis showed a strong association between " > 5 years duration" of estrogen or estrogen combined with progesterone use and BCIS. Furthermore, current use of any HT is associated with increased risk of BCIS in cohort studies. Additional well-designed large studies are now required to validate this association in different populations.


Assuntos
Neoplasias da Mama/etiologia , Carcinoma Ductal de Mama/etiologia , Carcinoma Intraductal não Infiltrante/etiologia , Terapia de Reposição de Estrogênios/efeitos adversos , Pós-Menopausa , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Fatores de Risco
14.
World J Surg Oncol ; 10: 165, 2012 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22906075

RESUMO

BACKGROUND: Mounting clinical and experimental data suggest that the migration of tumor cells into lymph nodes is greatly facilitated by lymphangiogenesis. Vascular endothelial growth factor (VEGF)-C and D have been identified as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis. The purpose of this study was to investigate the location of lymphangiogenesis driven by tumor-derived VEGF-C/D in breast cancer, and to determine the role of intratumoral and peritumoral lymphatic vessel density (LVD) in lymphangiogenesis in breast cancer. METHODS: The expression levels of VEGF-C/D were determined by immunohistochemistry, and intratumoral LVD and peritumoral LVD were assessed using immunohistochemistry and the D2-40 antibody in 73 patients with primary breast cancer. The associations of intratumoral LVD and peritumoral LVD with VEGF-C/D expression, clinicopathological features and prognosis were assessed. RESULTS: VEGF-C and D expression were significantly higher in breast cancer than benign disease (P < 0.01). VEGF-C (P < 0.001) and VEGF-D (P = 0.005) expression were significantly associated with peritumoral LVD, but not intratumoral LVD. Intratumoral LVD was associated with tumor size (P = 0.01). Peritumoral LVD was significantly associated with lymph node metastasis (LNM; P = 0.005), lymphatic vessel invasion (LVI; P = 0.017) and late tumor,node, metastasis (TNM) stage (P = 0.011). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, overall survival and disease-free survival in multivariate analysis. CONCLUSIONS: This study suggests that tumor-derived VEGF-C/D induce peritumoral lymphangiogenesis, which may be one mechanism that leads to lymphatic invasion and metastatic spread. Peritumoral LVD has potential as an independent prognostic factor in breast cancer patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Linfangiogênese , Vasos Linfáticos/patologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator D de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Vasos Linfáticos/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
15.
PLoS One ; 7(6): e38150, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22761669

RESUMO

AIM: To determine the pharmacogenetics of platinum-based chemotherapy in Non Small Cell Lung Cancer (NSCLC) patients. METHODS: Publications were selected from PubMed, Cochrane Library and ISI Web of Knowledge. A meta-analysis was conducted to determine the association between genetic polymorphisms and platinum-based chemotherapy by checking odds ratio (OR) and 95% confidence interval (CI). RESULTS: Data were extracted from 24 publications, which included 11 polymorphisms in 8 genes for meta-analysis. MDR1 C3435T (OR = 1.97, 95% CI: 1.11-3.50, P = 0.02), G2677A/T (OR = 2.61, 95% CI: 1.44-4.74, P = 0.002) and GSTP1 A313G (OR = 0.32, 95% CI: 0.17-0.58, P = 0.0002) were significantly correlated with platinum-based chemotherapy in Asian NSCLC patients. CONCLUSION: Attention should be paid to MDR1 C3435T, G2677A/T and GSTP1 A313G for personalized chemotherapy treatment for NSCLC patients in Asian population in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Farmacogenética , Platina/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética , Prognóstico
16.
CNS Neurosci Ther ; 18(8): 647-51, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22630058

RESUMO

AIMS: Some study found that ATP-binding cassette (ABC) efflux transporters play an important role in antiepileptic drug resistance, especially ABCB1 and ABCC2. The aims of this study were to evaluate the relationship between the genetic polymorphisms of ABCC2 and ABCB1 and the therapeutic efficacy of antiepileptic drugs (AEDs) in Chinese epileptic patients. METHODS: ABCB1 rs1045642 (3435C>T) and ABCC2 rs717620 (-24C>T), rs3740066 (3972C>T), and rs2273697 (1249G>A) polymorphisms loci in 537 Chinese epilepsy patients (217 drug resistant patients and 320 drug responders) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: ABCC2 rs717620 -24TT genotype was significantly associated with drug resistant epilepsy (odds ratio [OR]= 4.06 [1.79-9.20], P= 0.001). The OR values of ABCC2 rs717620 -24 CT+TT genotypes and ABCC2 rs3740066 (3972C>T) CT+TT genotypes were markedly higher in drug resistant patients (OR = 1.57 [1.08-2.29], P= 0.018; OR = 1.49 [1.02-2.18], P= 0.038, respectively) compared with responsive patients. ABCC2 rs2273697 (1249G>A) and ABCB1 rs1045642 (3435C>T) polymorphisms were not associated with drug resistant epilepsy. Linkage disequilibrium (LD) test showed that the ABCC2 rs717620 were in strong LD with rs2273697 (D'= 0.694) and rs3740066 (D'= 0.699). The frequencies of haplotypes TGT (ABCC2 -24C>T/ABCC2 1249G>A/ABCC2 3972C>T) in resistant patients was significantly higher than those in responsive patients (21.0% vs. 14.2%, P < 0.05). CONCLUSION: ABCC2-24C>T, 3972C>T polymorphisms and one ABCC2 haplotype is associated with AED resistance; ABCC2 1249G>A and ABCB1 3435C>T polymorphisms are not associated with AED resistance in our study. These data suggest that ABCC2 polymorphisms and haplotype may affect the response of antiepileptic drugs.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Resistência a Medicamentos , Epilepsia/epidemiologia , Feminino , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Adulto Jovem
17.
Med Oncol ; 29(4): 2594-600, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22562155

RESUMO

Breast cancer usually initially metastases to the sentinel lymph nodes (SLNs). Recent studies have demonstrated that tumor cells induce SLN lymphangiogenesis before metastasis in several malignancies. In addition, tumor-derived VEGF-C or VEGF-D may induce lymphangiogenesis and promote lymph node metastasis. To explore the mechanisms of lymph node metastasis in breast cancer, we investigated whether primary tumors induce SLN lymphangiogenesis before metastasis and determined the function of tumor-derived VEGF-C and VEGF-D in SLN lymphangiogenesis. Expression of VEGF-C and VEGF-D was examined using immunohistochemistry in 63 primary breast tumors. No significant relationships between VEGF-C and VEGF-D (P=0.420), and VEGF-C or VEGF-D expression and clinical parameters (age, tumor size, grade, hormonal receptor status, her-2 status) were observed (P>0.05). Expression of the lymphatic-specific markers VEGFR-3, Prox-1 and LYVE-1 was measured using quantitative real-time RT-PCR in uninvolved SLNs from 63 patients and compared to control lymph nodes from patients with benign breast disease. Expression of Prox-1 and LYVE-1 mRNA was significantly higher in uninvolved SLNs from breast cancer patients than that in control lymph nodes (P<0.01). Interestingly, expression of VEGFR-3, Prox-1 and LYVE-1 was significantly higher in SLNs from patients with high VEGF-C-expressing tumors than low VEGF-C-expressing tumors (P<0.05), but not VEGF-D-high-expressing tumors (P>0.05). This study demonstrates that primary breast tumors induce SLN lymphangiogenesis before metastasis occurs and that tumor-derived VEGF-C, but not VEGF-D, plays an important role in SLN lymphangiogenesis in breast cancer.


Assuntos
Neoplasias da Mama/patologia , Linfangiogênese , Biópsia de Linfonodo Sentinela , Fator C de Crescimento do Endotélio Vascular/fisiologia , Fator D de Crescimento do Endotélio Vascular/fisiologia , Adulto , Idoso , Feminino , Proteínas de Homeodomínio/genética , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Proteínas Supressoras de Tumor/genética , Fator C de Crescimento do Endotélio Vascular/análise , Fator D de Crescimento do Endotélio Vascular/análise , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Proteínas de Transporte Vesicular/genética
18.
Xenobiotica ; 42(8): 784-90, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22381135

RESUMO

Ginkgo biloba extract (GBE) is one of the most widely used herbal medicines in the world. It is often administered in combination with statins to treat diseases, especially some nervous system disorders. We aimed to investigate the influences of GBE on pharmacokinetics and efficacy of atorvastatin, which are currently unclear. Sixteen volunteers received a single oral dose of 40 mg atorvastatin, followed by a wash-out period of at least 5 days. Then the volunteers took 360 mg GBE daily for 14 days, followed by a single dose of 40 mg atorvastatin. Serial blood samples obtained over a period of 48 h after atorvastatin ingestion were subjected to determination of atorvastatin plasma concentrations and markers of cholesterol synthesis (lathosterol) and cholesterol absorption (sitosterol). With GBE administration, AUC0₋48, AUC(0-∞) and C(max) of atorvastatin were reduced by 14.27% (p = 0.005), 10.00% (p = 0.03) and 28.93% (p = 0.002), respectively; Vd/F and CL/F of atorvastatin were increased by 31.95% (p = 0.017) and 6.48% (p = 0.044). After 14 days of treatment, GBE has no significant effects on cholesterol-lowering efficacy of atorvastatin. This study suggests that GBE slightly decreases the plasma atorvastatin concentrations, but has no meaningful effect on the cholesterol-lowering efficacy of atorvastatin.


Assuntos
Ginkgo biloba/química , Ácidos Heptanoicos/sangue , Ácidos Heptanoicos/farmacocinética , Interações Ervas-Drogas , Extratos Vegetais/farmacologia , Pirróis/sangue , Pirróis/farmacocinética , Administração Oral , Adulto , Atorvastatina , Colesterol/sangue , Ácidos Heptanoicos/administração & dosagem , Humanos , Masculino , Pirróis/administração & dosagem , Resultado do Tratamento
19.
Biochem Biophys Res Commun ; 411(1): 32-9, 2011 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-21722625

RESUMO

OBJECTIVES: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H(2)O(2), we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. MATERIALS AND METHODS: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50µmol/L or 100µmol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. CONCLUSIONS: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Depuradores de Radicais Livres/farmacologia , Glucose/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Sequência de Bases , Células HEK293 , Heme Oxigenase-1/biossíntese , Humanos , Peróxido de Hidrogênio/toxicidade , Dados de Sequência Molecular , Fator 2 Relacionado a NF-E2/biossíntese , Espécies Reativas de Oxigênio/metabolismo
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