RESUMO
Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.
Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus/etiologia , Rejeição de Enxerto/etiologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Philadelphia/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
MiR-200b, a member of the microRNA-200 family, has been identified to be capable of suppressing glioma cell growth through targeting CREB1 or CD133. However, whether miR-200b affects the biological behavior (proliferation, invasion, and migration) of glioma cells is poorly understood. The aim of this study was to evaluate the effect of miR-200b on the biological behavior of glioma cells in vitro. MiRNA-200b mimics, miRNA-200b inhibitor, and mimic control were transfected into conventionally cultured glioma U251 cells, followed by measuring the expression of miR-200b and CD133 in transfected cells by RT-PCR; effect of miR-200b on CD133 mRNA 3'-UTR luciferase activity by luciferase reporter assay; proliferation activity of transfected U251 cells by MTT method; and changes in U251 cell invasion and migration by Transwell method after transfection. Compared to that in the miRNA-200b inhibitor, mimic control, and blank control groups, miRNA-200b expression was significantly increased and CD133 mRNA expression was significantly decreased in the mimic miRNA-200b group in a time-dependent manner (P < 0.05). Meanwhile, dual luciferase reporter assay showed that miR-200b could inhibit CD133 activity through binding to the 3'-UTR of CD133 mRNA (P < 0.05). Furthermore, the proliferation activity and invasion and migration abilities of U251 cells transfected with miRNA-200b mimic were significantly decreased (P < 0.05). In conclusion, overexpression of miR-200b inhibited the proliferation, invasion, and migration of glioma cells possibly through targeting CD133.
Assuntos
Antígeno AC133/genética , Glioma/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Antígeno AC133/metabolismo , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , MicroRNAs/biossíntese , MicroRNAs/metabolismo , Neoplasias do Sistema Nervoso/genética , Neoplasias do Sistema Nervoso/metabolismo , Neoplasias do Sistema Nervoso/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , TransfecçãoRESUMO
We conducted a case-control study to assess the association between single nucleotide polymorphisms in the ERCC5 promoter (rs2094258 and rs751402) and development of gastric cancer in a Chinese population. This investigation included 184 patients with pathologically diagnosed gastric cancer and 206 healthy subjects recruited between October 2012 and December 2014. The genotyping of ERCC5 rs2094258 and rs751402 variants was performed by polymerase chain reaction coupled with restriction fragment length polymorphism. Genotype distributions of these polymorphisms conformed to Hardy-Weinberg equilibrium in both patient (P = 0.25 for rs2094258 and P = 0.61 for rs751402) and control groups (P = 0.48 for rs2094258 and P = 0.42 for rs751402). Using unconditional logistic regression analysis, we found that neither of these ERCC5 variants was associated with increased risk of gastric cancer under co-dominant, dominant, or recessive models (P < 0.05). In conclusion, we suggest that the rs2094258 and rs751402 polymorphisms are not connected to the development of this disease under codominant, dominant, and recessive models.
Assuntos
Proteínas de Ligação a DNA/genética , Endonucleases/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Adulto , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Gástricas/patologiaRESUMO
Tail fat content affects meat quality, and it varies in different sheep breeds. Theoretically, lipid metabolism contributes to variation in tail fat content. Tail length, tail width, and tail girth were measured in live Tong sheep (with both short fat tail and long fat tail), Shaanbei fine wool sheep (long thin tail), Tan sheep (short fat tail), Kazakh sheep (hip fat tail), and Tibetan sheep (short thin tail). The expression levels of genes related to tail adipose tissue lipid metabolism were investigated, which included lipogenetic genes (PPARγ and FAS) and lipolytic gene (HSL). Differences were observed (P < 0.05) in PPARγ mRNA expression levels in the different breeds; FAS mRNA expression levels did not differ (P > 0.05) in Tong sheep with short fat tail, Tong sheep with long fat tail, Shaanbei fine wool sheep, and Tibetan sheep; HSL mRNA expression levels were not different (P > 0.05) in Tong sheep. PPARγ and HSL protein expression levels differed (P < 0.05) between the different breeds; FAS protein expression levels were different (P < 0.05) in Tong sheep with long fat tails, Tan sheep, Kazakh sheep, and Tibetan sheep, but did not differ (P > 0.05) in Tong sheep with short fat tails and Shaanbei fine wool sheep. These results provide useful information to further understand the function of PPARγ, FAS, and HSL in sheep tail lipid metabolism, which should be applicable to studies on the regulation of fat deposition and improvement of meat quality.
Assuntos
Ácido Graxo Sintases/genética , Regulação Enzimológica da Expressão Gênica , PPAR gama/genética , Fenótipo , Ovinos/genética , Esterol Esterase/genética , Cauda/anatomia & histologia , Animais , Ácido Graxo Sintases/metabolismo , Metabolismo dos Lipídeos , PPAR gama/metabolismo , Ovinos/classificação , Ovinos/metabolismo , Esterol Esterase/metabolismoRESUMO
We investigated the role of bacterial biofilms in stimulating T helper 17 (Th17) cells in infected organisms. The formation of bacterial biofilms isolated from clinical lavage fluid samples was measured. Th17 cells and interleukin 17 (IL-17) levels in the peripheral blood of healthy individuals, people infected by biofilm bacteria, people infected by non-biofilm bacteria, and in the lavage fluid from people infected by bacteria were determined. Differences in those data were tested using the SPSS 17.0 statistical software. Th17 cells and IL-17 levels in the peripheral blood of biofilm bacteria-infected people, non-biofilm bacteria-infected people, and healthy controls were 0.59 ± 0.18% and 108.8 ± 20.5 pg/mL; 0.58 ± 0.18% and 100.1 ± 20.7 pg/mL; and 0.55 ± 0.17% and 100.0 ± 21.4 pg/mL, respectively; there were no statistically significant differences (P > 0.05). Th17 cells and IL-17 levels in the lavage fluid of biofilm bacteria-infected people and non-biofilm bacteria-infected people were 1.37 ± 0.34% and 157.4 ± 30.8 pg/mL; and 1.11 ± 0.21% and 136.2 ± 24.3 mg/mL, respectively; the differences were statistically significant (P < 0.05). Bacterial biofilms can increase the expression levels of Th17 cells and IL-17 in local infections; this may be the mechanism by which chronic injuries are caused by biofilm infections.
Assuntos
Acinetobacter/fisiologia , Biofilmes/crescimento & desenvolvimento , Pseudomonas aeruginosa/fisiologia , Células Th17/imunologia , Líquido da Lavagem Broncoalveolar , Humanos , Interleucina-17/sangueRESUMO
Congenital cataract is caused by reduced transparency of the lens resulting from metabolic disorders during the fetal period. The disease shows great heterogeneity both clinically and genetically. We identified a 4-generation ethnic Han Chinese family affected by autosomal dominant congenital perinuclear cataract. The patients underwent full clinical and ophthalmologic examinations to rule out any concomitant disorders. Blood samples were collected and genomic DNA was extracted. Potential mutations in the candidate gene alpha A crystallin (CRYAA) were screened. Prenatal diagnosis was then provided for a fetus of the affected proband by chorionic villus sampling. In all patients, DNA sequencing of the CRYAA gene revealed a novel 3-bp deletion mutation in exon 3 (c.246_248delCGC), which led to deletion of codon 117 encoding arginine (p.117delR) in the peptide chain. The same mutation was not found among unaffected and healthy individuals. Bioinformatic analysis revealed that although the c.246_248delCGC is an 'in-frame' mutation, removal of arginine resulted in a significant change in the protein structure. The fetus did not possess this mutation and was confirmed to be healthy at 1-year follow-up. A novel disease-causing mutation, c.246_248delCGC (p.117delR), of the CRYAA gene has been identified in a Chinese family with autosomal-type perinuclear congenital cataracts. This is also the first report of prenatal diagnosis of this type of congenital cataract.
Assuntos
Povo Asiático/genética , Pareamento de Bases/genética , Catarata/congênito , Catarata/genética , Cristalinas/genética , Genes Dominantes , Deleção de Sequência/genética , Adulto , Sequência de Bases , China , Biologia Computacional , Feminino , Seguimentos , Heterozigoto , Humanos , Recém-Nascido , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
To find Epstein-Barr virus (EBV) strains with genetic variations of EBV latent membrane protein 1 (EBV-LMP1) from nasopharyngeal carcinoma (NPC), the full-length DNA of LMP1 genes from 21 NPC biopsies obtained in Hunan province in southern China was amplified and sequenced. Our sequences were compared to those previously reported by the Clustal V method. Results showed that all 21 sequences displayed two amino acid changes most frequently in LMP1 of CD4+ T cell epitopes at codons 144 (F-->I, 21/21) and 212 (G-->S, 19/21) or (G-->N, 2/21). We also show that type A EBV strain is prevalent in the cases of NPC from Hunan province with a 30-bp 18/21 deletion, and we highlight that this deletion resulted in loss of one of the CD4+ T cell-restricted epitopes. The other 3 sequences without this deletion all had a change at codon 344 (G-->D). Furthermore, in the major epitope sequence of CD8+ T cells restricted by HLA-A2, all 21 sequences showed changes at codons 126 (L-->F) and 129 (M-->I). Our study discovered that one of the 21 sequence variations harbored a new change at codon 131 (W-->C), and 5/21 specimens showed another novel change at codon 115 (G-->A) in the major epitope sequence of CD8+ T cells restricted by HLA-A2. Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.
Assuntos
Epitopos de Linfócito T/genética , Variação Genética , Antígeno HLA-A2/genética , Neoplasias Nasofaríngeas/virologia , Proteínas da Matriz Viral/genética , Adulto , Sequência de Aminoácidos , Biópsia , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Epitopos de Linfócito T/análise , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
To find Epstein-Barr virus (EBV) strains with genetic variations of EBV latent membrane protein 1 (EBV-LMP1) from nasopharyngeal carcinoma (NPC), the full-length DNA of LMP1 genes from 21 NPC biopsies obtained in Hunan province in southern China was amplified and sequenced. Our sequences were compared to those previously reported by the Clustal V method. Results showed that all 21 sequences displayed two amino acid changes most frequently in LMP1 of CD4+ T cell epitopes at codons 144 (F arrow right I, 21/21) and 212 (G arrow right S, 19/21) or (G arrow right N, 2/21). We also show that type A EBV strain is prevalent in the cases of NPC from Hunan province with a 30-bp 18/21 deletion, and we highlight that this deletion resulted in loss of one of the CD4+ T cell-restricted epitopes. The other 3 sequences without this deletion all had a change at codon 344 (G arrow right D). Furthermore, in the major epitope sequence of CD8+ T cells restricted by HLA-A2, all 21 sequences showed changes at codons 126 (L arrow right F) and 129 (M arrow right I). Our study discovered that one of the 21 sequence variations harbored a new change at codon 131 (W arrow right C), and 5/21 specimens showed another novel change at codon 115 (G arrow right A) in the major epitope sequence of CD8+ T cells restricted by HLA-A2. Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.