RESUMO
OBJECTIVE: Increasing evidence demonstrates that immune signature plays an important role in the prognosis of gastric cancer (GC). We aimed to develop and validate a robust immune-related gene pair (IRGP) signature for predicting the prognosis of GC patients. METHODS: RNA-Seq data and corresponding clinical information of GC cohort were downloaded from the TCGA (The Cancer Genome Atlas Program) data portal. GSE84437 and GSE15459 microarray datasets were included as independent external cohorts. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to build the best prognostic signature. All patients were classified into the high immune-risk and low immune-risk groups via the optimal cut-off of the signature scores determined by time-dependent receiver-operating characteristic (ROC) curve analysis. The prognostic role of the signature was measured by a log-rank test and a Cox proportional hazard regression model. RESULTS: 14 immune gene pairs consisting of 25 unique genes were identified to construct the immune prognostic signature. High immune-risk groups showed poor prognosis in the TCGA datasets and GSE84437 datasets as well as in the GSE15459 datasets (all P < 0.001). The 14-IRGP signature was an independent prognostic factor of GC after adjusting for other clinical factors (P < 0.05). Functional analysis revealed that DNA integrity checkpoint, DNA replication, T-cell receptor signaling pathway, and B-cell receptor signaling pathway were enriched in the low immune-risk groups. B cells naive and Monocytes were significantly higher in the high-risk group, and B-cell memory and T-cell CD4 memory activated were significantly higher in the low-risk group. The prognostic signature based on IRGP reflected infiltration by several types of immune cells. CONCLUSION: The novel proposed clinical-immune signature is a promising biomarker for prediction overall survival in patients with GC and providing new insights into the treatment strategies.
Assuntos
Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Replicação do DNA , Bases de Dados Genéticas , Bases de Dados de Ácidos Nucleicos , Conjuntos de Dados como Assunto , Expressão Gênica , Humanos , Memória Imunológica , Linfócitos do Interstício Tumoral , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Regressão , Neoplasias Gástricas/mortalidadeRESUMO
This study was aimed to investigate the effect of green tea extract (GTE) combined with brisk walking on lipid profiles and the liver function in overweight and obese men. Twenty-four participants were randomized to either the GTE group or the placebo group for 12 weeks with a 4-week follow-up. The walking program consisted of four 60-min-sessions/week and all participants were asked to consume two GTE (150mg) or placebo tablets daily. After 12-week intervention, GTE group resulted in a significant difference in the low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels when compared to placebo group (P < 0.01). There was also a significant reduction in the aspartate aminotransferase levels (P < 0.01) in the GTE group, but no change in the placebo group (P >0.05). There was no change in the triglyceride or high-density lipoprotein cholesterol (HDL-C) levels in the placebo group, but a significant reduction was noted in the HDL-C levels in the GTE group (P < 0.05). GTE combined with brisk walking resulted in a significant change in the LDL-C and TC levels, however, a significant reduce in HDL-C in the GTE group. The study has a more positive effect on the liver function than brisk walking alone.
Assuntos
Catequina , Caminhada , Humanos , Lipídeos , Fígado , Masculino , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Extratos Vegetais/farmacologia , CháRESUMO
ABSTRACT A complete linkage disequilibrium between the SNP (SNP B) in BCDO2 gene and the yellow skin phenotype in European domestic chicken has been reported. Here, we genotyped the reported SNPs (SNP A, SNP B, and SNP C) of the BCDO2 gene in 183 Chinese Indigenous chickens from 11 breeds/populations, including 57 yellow, 17 white, and 109 black skin chickens. The frequency of all three SNPs were significantly different between yellow and white skin chickens (p 0.01). In black skin chickens, a high frequency of the heterozygous genotype (AG) in SNP A (0.51) and SNP B (0.48) was observed. A total of three haplotypes (AAA, AGA, and GAA) from these three SNPs were obtained. Frequencies of the proposed yellow skin-associated haplotype AGA in yellow skin, white skin, and black skin chickens were 0.81, 0.35, and 0.56, respectively. The results showed that the yellow skin phenotype of the evaluated birds has not been under selection, and that the BCDO2 gene in black skin chickens, evolutionally may undergo a transition phase from yellow to white skin chicken. We concluded that, the SNPs of BCDO2 gene not only can be used to determine whether the chicken was subjected to selection, but may also be used as a marker when selecting for the preferred skin color in chicken breeding programs.
Assuntos
Animais , Aves Domésticas/anatomia & histologia , Aves Domésticas/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
ABSTRACT A complete linkage disequilibrium between the SNP (SNP B) in BCDO2 gene and the yellow skin phenotype in European domestic chicken has been reported. Here, we genotyped the reported SNPs (SNP A, SNP B, and SNP C) of the BCDO2 gene in 183 Chinese Indigenous chickens from 11 breeds/populations, including 57 yellow, 17 white, and 109 black skin chickens. The frequency of all three SNPs were significantly different between yellow and white skin chickens (p 0.01). In black skin chickens, a high frequency of the heterozygous genotype (AG) in SNP A (0.51) and SNP B (0.48) was observed. A total of three haplotypes (AAA, AGA, and GAA) from these three SNPs were obtained. Frequencies of the proposed yellow skin-associated haplotype AGA in yellow skin, white skin, and black skin chickens were 0.81, 0.35, and 0.56, respectively. The results showed that the yellow skin phenotype of the evaluated birds has not been under selection, and that the BCDO2 gene in black skin chickens, evolutionally may undergo a transition phase from yellow to white skin chicken. We concluded that, the SNPs of BCDO2 gene not only can be used to determine whether the chicken was subjected to selection, but may also be used as a marker when selecting for the preferred skin color in chicken breeding programs.(AU)
Assuntos
Animais , Aves Domésticas/anatomia & histologia , Aves Domésticas/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Increasing evidence suggests that the cerebrospinal ï¬uid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia. The levels of soluble FKN (sFKN) were markedly upregulated along with the increase in FKN mRNA level in rats subjected to chronic constriction injury. In addition, injection of FKN-neutralizing antibody into the lateral ventricle alleviated neuropathic pain-related behavior followed by reduction in microglial activation in the CSF-contacting nucleus. The results indicate that inhibition of FKN release by the CSF-contacting nucleus may ameliorate neuropathic pain clinically.
Assuntos
Núcleo Celular/metabolismo , Líquido Cefalorraquidiano/metabolismo , Quimiocina CX3CL1/metabolismo , Dor Crônica/metabolismo , Neuralgia/metabolismo , Limiar da Dor/fisiologia , Animais , Modelos Animais de Doenças , Injeções Intraventriculares , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para CimaRESUMO
Expressed sequence tags (ETSs) are the sources of microsatellite development. In this study, we isolated and characterized microsatellite markers for Odontobutis potamophila by using Illumina RNA-sequencing. We sequenced a large number of ESTs and screened 200 potential microsatellites. Consequently, a total of 56 novel polymorphic microsatellite repeat markers were identified in thirty-two individuals from a wild population area (Jiande, Zhejiang Province, China). The number of alleles per locus varied from two to eight, the observed heterozygosity (HO) ranged from 0.03571 to 0.9375, and the expected heterozygosity (HE) ranged from 0.14326 to 0.81549. The average number of alleles, HO, and HE were 5.0, 0.4467, and 0.5518, respectively. By the calculation, the range of polymorphism information content (PIC) was 0.1177-0.8492. Most of the loci showed moderate or high polymorphism. These newly developed EST-simple sequence repeat (EST-SSR) markers would serve as an efficient tool for analyzing population connectivity and provide sufficient information for genetic diversity research, parentage, and molecular breeding of O. potamophila and other fishes with similar genetic relationship.
Assuntos
Etiquetas de Sequências Expressas , Repetições de Microssatélites , Perciformes/genética , Transcriptoma , Alelos , Animais , Marcadores Genéticos , Heterozigoto , Polimorfismo GenéticoRESUMO
Root-knot nematodes (Meloidogyne spp) are destructive agricultural pests that reduce the productivity of cultivated vegetables worldwide, especially when vegetables are cropped continuously in greenhouses. Cucumbers (Cucumis sativus L.), in particular, suffer extensive damage due to root-knot nematodes, and only a few wild species are known to be resistant. Grafting of cultivated plants to rootstocks of known resistant germplasms could be an effective method to resolve this problem. In this study, 21 cucumber germplasms and seven rootstocks were evaluated for resistance based on the growth of cucumber seedlings and resistance indexes to Meloidogyne incognita, which were surveyed 25 days after inoculation with M. incognita. Cluster analysis and principal component analysis (PCA) were used to investigate the resistance of 21 cucumber germplasms and seven rootstocks based on their growth and resistance indexes after inoculation with M. incognita. These analyses showed that the 21 germplasms and seven rootstocks could be divided into three groups based upon their resistance levels: moderately resistant, susceptible, and highly susceptible to M. incognita. All 21 cucumber germplasms exhibited susceptibility or high susceptibility to M. incognita and most rootstocks exhibited moderate resistance. The PCA results were consistent with those of the clustering analysis. The Jinyou No.1 cultivar had the highest resistance to M. incognita among the 21 cucumber germplasms, and Huangzhen No.1 cultivar had the highest resistance among the seven rootstock cultivars.
Assuntos
Cucumis/genética , Resistência à Doença/genética , Animais , Cucumis/imunologia , Cucumis/parasitologia , Variação Genética , Raízes de Plantas/genética , Raízes de Plantas/parasitologia , Sementes/genética , Sementes/parasitologia , Tylenchoidea/patogenicidadeRESUMO
Cardiomyocyte apoptosis plays key roles in the pathogenesis of heart diseases such as myocardial infarction. MicroRNAs are important regulators of gene expression, which are also involved in the regulation of cardiomyocyte apoptosis. However, cardiomyocyte apoptosis regulated by microRNA (miR)-122 is largely unexplored. The aim of this study focused on the role of miR-122 in cardiomyocyte apoptosis. Cardiomyocytes were isolated from neonatal mice and primarily cultured. MiR-122 mimic and inhibitor were transfected to cardiomyocytes and verified by qRT-PCR. Cell viability and apoptosis post-transfection were assessed by MTT assay and flow cytometry, respectively. Changes in expression of caspase-8 were quantified by qRT-PCR and western blot. Results showed that miR-122 mimic and inhibitor successfully induced changes in miR-122 levels in cultured cardiomyocytes (P<0.01). MiR-122 overexpression suppressed viability and promoted apoptosis of cardiomyocytes (P<0.05), and miR-122 knockdown promoted cell viability and inhibited apoptosis (P<0.05). The mRNA and protein levels of caspase-8 were elevated by miR-122 overexpression (P<0.01) and reduced by miR-122 knockdown (P<0.001). These results suggest an inductive role of miR-122 in cardiomyocyte apoptosis, which may be related to its regulation on caspase-8.
Assuntos
Apoptose/genética , Caspase 8/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Miócitos Cardíacos/patologia , Animais , Animais Recém-Nascidos , Expressão Gênica/fisiologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
PURPOSE: Changes in EGFR profiles of non small cell lung cancer (NSCLC) patients correlates to clinical outcome. Extracting quality tumor tissue remains a challenge for molecular profiling. Our study aims to ascertain the clinical relevance of urinary cell free DNA as an alternative tumor material source. METHODS: 150 patients with activating EGFR mutation and received EGFR-TKIs were recruited to participate in the serial monitoring study. Matched primary tumor samples were taken together with blood and urine specimens before the initiation of TKIs. The EGFR mutation testing was performed and quantified using ddPCR. For serial time point measurements, urine and blood samples were extracted at 1-month intervals for duration of 9 months. RESULTS: Urinary ctDNA yielded a close agreement of 88 % on EGFR mutation status when compared to primary tissue at baseline. Almost all samples detected via urine specimens were uncovered in plasma samples. Analysis of urinary cell free DNA at different time points showed a strong correlation to treatment efficacy. Interestingly, a secondary EGFR mutation T790M was detected for 53 % of the patients during monitoring. The results were corroborated with the plasma ctDNA analysis. The T790M+ group had a reduced median survival when compared to the wildtype group. CONCLUSION: Urinary cell free DNA may be a potential alternative to conventional primary tissue based EGFR mutation testing. Our findings showed that the assay sensitivity was comparable to results from blood plasma. Urinary samples being noninvasive and readily available have clinical utility for monitoring of EGFR TKI treatment.
Assuntos
Biomarcadores Tumorais/urina , Carcinoma Pulmonar de Células não Pequenas/urina , DNA de Neoplasias/urina , Receptores ErbB/genética , Mutação/genética , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/urina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , DNA de Neoplasias/genética , Receptores ErbB/urina , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/urina , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/metabolismo , Reação em Cadeia da Polimerase , Prognóstico , Taxa de SobrevidaRESUMO
Reciprocal translocation is closely associated with male infertility and recurrent miscarriages. Balanced reciprocal translocations associated with reproductive failures are predominantly observed on chromosome 1. Additionally, infertile male patients present a number of breakpoints throughout chromosome 1. A translocation breakpoint might interrupt the structure of an important gene, leading to male infertility. Here, we report the breakpoints on chromosome 1 translocation and the clinical features presented in carriers, to enable informed genetic counseling of these patients. Balanced reciprocal translocations were found in 1.57% of the tested patients. Among 82 patients, 23 patients (28.05%) were carriers of the chromosome 1 translocation: 12 presented pre-gestational infertility with clinical manifestations of azoospermia or oligozoospermia, while 11 patients presented gestational infertility (able to conceive but with a tendency to miscarry or give birth to a stillborn). The breakpoint at 1p22 was predominantly observed in these patients; additionally, breakpoints at 1p31.2, 1p10, and 1q25 were associated with gestational infertility. Breakpoints at 1p13, 1q12, and 1q21 were associated with pre-gestational infertility. These results suggested that breakpoints at 1p32, 1p13, and 1q21 were predominantly associated with pre-gestational infertility, while that at 1q25 was associated with gestational infertility. Chromosome 1 translocation carriers with infertility presenting as azoospermia or oligospermia should be counseled on chromosomal breakpoints and the different molecular technologies available to facilitate reproduction.