RESUMO
Deregulation of cardiac miRNA gene-regulatory networks is a feature of different heart diseases, including ischemic (ICM) and nonischemic (NICM) cardiomyopathy. Here, based on the paired miRNA and mRNA expression profiles in ICM and NICM, we identified the differentially expressed miRNAs and mRNAs and the expression signatures distinguishing ICM/NICM from control samples. Furthermore, we constructed a functional miRNA network for each disease. Analysis of the topological features of these networks revealed that the Wnt signaling pathway and cell cycle (de)regulation play critical roles in the development of ICM and NICM. In addition, comparison of the miRNA and mRNA functional profiles revealed that their expression patterns in ICM and NICM differ. These findings revealed hundreds of novel heart-failure-related miRNAs with important regulatory functions. In summary, RNA-seq-based transcriptome profiling in the failing human heart revealed a complex transcriptional regulation associated with the disease. The newly uncovered importance of miRNAs in disease pathogenesis highlights their value as potential diagnostic and therapeutic targets.
Assuntos
Cardiomiopatias/genética , Redes Reguladoras de Genes , MicroRNAs/genética , Isquemia Miocárdica/genética , Transcriptoma , Estudos de Casos e Controles , Humanos , MicroRNAs/metabolismo , Miocárdio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Via de Sinalização WntRESUMO
Tea (Camellia sinensis L.) is a thermophilic evergreen woody plant that has poor cold tolerance. The SAD gene plays a key role in regulating fatty acid synthesis and membrane lipid fluidity in response to temperature change. In this study, full-length SAD cDNA was cloned from tea leaves using rapid amplification of cDNA ends and polymerase chain reaction (PCR)-based methods. Sequence analysis demonstrated that CsSAD had a high similarity to other corresponding cDNAs. At 25°C, the CsSAD transcriptional level was highest in the leaf and lowest in the stem, but there was no obvious difference between the root and stem organs. CsSAD expression was investigated by reverse transcription-PCR, which showed that CsSAD was upregulated at 4° and -5°C. At 25°C, CsSAD was induced by polyethylene glycol, abscisic acid, and wounding, and a similar trend was observed at 4°C, but the mean expression level at 4°C was lower than that at 25°C. Under natural cold acclimation, the 'CsCr05' variety's CsSAD expression level increased before decreasing. The CsSAD expression level in variety 'CsCr06' showed no obvious change at first, but rapidly increased to a maximum when the temperature was very low. Our study demonstrates that CsSAD is upregulated in response to different abiotic conditions, and that it is important to study the stress resistance of the tea plant, particularly in response to low temperature, drought, and wounding.
Assuntos
Adaptação Fisiológica , Camellia sinensis/enzimologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Estearoil-CoA Dessaturase/genética , Sequência de Aminoácidos , Camellia sinensis/genética , Camellia sinensis/fisiologia , Clonagem Molecular , Temperatura Baixa , Secas , Dados de Sequência Molecular , Filogenia , Componentes Aéreos da Planta/enzimologia , Componentes Aéreos da Planta/fisiologia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/fisiologia , Alinhamento de Sequência , Estearoil-CoA Dessaturase/química , Estearoil-CoA Dessaturase/metabolismoRESUMO
Zinc (Zn) is important for male mammalian reproduction. In this study, we sought to clarify the role of Zn in heat-induced testicular damage in mice. Eighteen mice were divided into either control (con), heat (heat) and heat plus Zn (H+Zn) treatment groups, and fed diets containing 60 (con and heat groups) or 300 (H+Zn group) mg/kg Zn sulfate for one month. Mice in the con group were then maintained at 25°C, while mice in heat and H+Zn groups were exposed to 40°C for 2 h daily, for eight days. Mouse testes and serum from each animal were analyzed. Zinc levels in serum and testes were positively correlated to Zn feed concentrations. Mice in the heat group had higher testes index than those in the other two groups (7.22 ± 0.75, heat; 4.92 ± 0.20, con; 4.80 ± 0.30 mg/g, H+Zn; P < 0.05). Testicular antioxidant status showed malondialdehyde levels in heat group mice were increased compared to control mice (2.34 ± 0.15 versus 1.55 ± 0.23 nmol/mg protein; P < 0.05), and Cu-Zn superoxide dismutase (SOD) level differed between heat and H+Zn groups (14.04 ± 0.74 versus 18.27 ± 1.53 U/mg protein; P < 0.05). Testicular Cu-Zn SOD protein expression levels were significantly lower in the heat than in the control group (0.30 ± 0.11 versus 1.22 ± 0.13; P < 0.05). These results suggest that dietary Zn may elevate the activity and protein concentration of Cu-Zn SOD, to attenuate testicular oxidative stress induced by heat exposure.
Assuntos
Estresse Oxidativo , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Zinco/farmacologia , Animais , Suplementos Nutricionais , Temperatura Alta/efeitos adversos , Masculino , Malondialdeído/metabolismo , Camundongos , Superóxido Dismutase/genética , Testículo/metabolismo , Regulação para Cima , Zinco/administração & dosagem , Zinco/sangueRESUMO
Numerous studies have evaluated the relationship between the T241M polymorphism of the X-ray repair cross-complementing group 3 (XRCC3) gene and colorectal cancer (CRC) risk. However, the specific relationship remains controversial. We conducted meta-analysis to investigate the relationship between the XRCC3 T241M polymorphism and CRC risk. The PubMed and Embase databases were searched for relevant studies investigating the relationship between the XRCC3 T241M polymorphism and CRC risk. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the possible relationship. Thirteen individual case-control studies, including 4720 cases and 6104 controls, were identified and included in this meta-analysis. Meta-analyses revealed no relationship between the XRCC3 T241M polymorphism and CRC risk (TT vs MM: OR = 0.85, 95%CI = 0.63-1.14; TT vs MT: OR = 0.87, 95%CI = 0.68-1.10; dominant model: OR = 1.18, 95%CI = 0.92-1.50; recessive model: OR = 0.87, 95%CI = 0.69-1.11). In the further subgroup analysis by ethnicity, we found no direct relationship between the polymorphism and CRC risk in either Asians or Europeans. Our findings demonstrated that the T241M polymorphism in the XRCC3 gene may not be a risk factor for CRC development.
Assuntos
Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Povo Asiático , Neoplasias Colorretais/patologia , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População BrancaRESUMO
The aims of this study were to explore the effects of Astragaloside IV on diabetic nephropathy (DN) rats. A total of 38 male Sprague-Dawley (SD) rats were divided into three groups: 10 in the normal (control) group, 14 in the DN model group, and 14 in the AS-IV group. Treatment began one week after the streptozotocin DN model was successfully established. Blood glucose and urine micro-albumin levels were measured every four weeks. After being treated for 12 weeks, all SD rats were sacrificed for blood and renal specimen collec-tion. Renal cortex specimens were observed after hematoxylin and eo-sin and Masson staining. Expression levels of protein ß1, ß1-integrin-linked protein kinase (ILK) and α-actinin-4 were also measured. After eight weeks of intervention, blood glucose levels in the AS-IV group decreased significantly when compared with those of the model group (P < 0.01). By the end of the twelfth week, the urine micro-albumin levels showed significant differences (P < 0.01) between the AS-IV and model groups, and the expression levels of integrin ß1, ILK, and α-actinin-4 also showed significant differences (P < 0.05, respectively). Concomitantly, expression levels of integrin ß1, ILK, and α-actinin-4 in the model group were significantly different from those of normal group (P < 0.05). These results suggest that AS-IV can be quite effective in decreasing blood glucose levels, reducing urine albumin excretion, and improving the adhesion function of potocytes, and can thus delay the development of DN.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Saponinas/administração & dosagem , Triterpenos/administração & dosagem , Actinina/genética , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Regulação da Expressão Gênica , Humanos , Integrina beta1/genética , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Proteínas Serina-Treonina Quinases/genética , RatosRESUMO
PURPOSE: To explore the altered different expression of miRNAs and the mechanisms underlying the relapse and metastasis of pancreatic cancer. MATERIALS AND METHODS: The most differentially expressed miRNAs were analyzed by gene ontology (GO) term analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein interaction analysis. The potentially regulated target genes of the most differentially expressed miRNAs were also analyzed further by GO term analysis and KEGG pathway analysis, and quantitated by qRT-PCR. RESULTS: In total, we found 12 miRNAs displayed at least a 30-fold increase or decrease in expression of carcinoma and relapse vs. para-carcinoma human pancreatic cancer (C/R vs. P). In addition, our study found that pancreatic cancer was related to pathways in cancer, including Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway. CONCLUSIONS: The differential expressed miRNAs and their predicted target genes that involved in Jak-STAT signaling pathway, MAPK signaling pathway and PPAR signaling pathway indicating their potential roles in pancreatic carcinogenesis and progress.
Assuntos
Carcinoma/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Neoplasias Pancreáticas/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Janus Quinases/genética , Sistema de Sinalização das MAP Quinases , Análise de Sequência com Séries de Oligonucleotídeos , Pâncreas/química , Receptores Ativados por Proliferador de Peroxissomo/genética , Fatores de Transcrição STAT/genética , Transcriptoma , Regulação para CimaRESUMO
More than 40 oncogenes associated with non-small cell lung cancer (NSCLC) have been identified with varied gene expression. The correlations between specific clinical characteristics and oncogene expression in NSCLC patients were examined. From October 2011 to September 2012, a total of 60 patients with NSCLC (male:female, 34:24; mean age, 59.5 ± 10.6 years; age range, 31-81 years) were diagnosed and evaluated for treatment with radical resection at a single facility. Eligible patients exhibiting tumor node metastasis (TNM) stage I-III NSCLC confirmed by post-surgical pathology were included. mRNA expression was detected by branched DNA-liquidchip technology (bDNA-LCT) and mutations were detected at EGFR exons 18, 19, 20, and 21, KRAS exons 2 and 3, BRAF and PIK3CA exons 9 and 20. Correlations between gene expression at mutations and clinical characteristics of gender, age, histological type, degree of differentiation, smoking status, immunohistochemical (IHC) evaluation of TTF-1, TNM staging, and discrete age ("nage") were examined. Significant associations were observed between IHC staining for TTF-1 and histological type (P = 0.00001) and with BRAC1, TYMS, RRM1, and TUBB3 expression (P = 0.0187, 0.0051, 0.024, and 0.0238, respectively). Significant cross-correlations were observed between TYMS, BRAC1, TOP2A, STMN1, TUBB3, and RRM1 expression (P < 0.05), but not between EGFR exon 21, KRAS exon 2, and PIK3CA exon 9 expression and any other mutation expression (P > 0.05). Relationships between clinical characteristics and oncogene expression in NSCLC, particularly those of TTF-1 level and smoking status, may be useful indicators of prognosis and development of anti-cancer drug resistance.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Classe I de Fosfatidilinositol 3-Quinases , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Éxons/genética , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Proteínas Nucleares/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fumar , Fator Nuclear 1 de Tireoide , Fatores de Transcrição/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismoRESUMO
To investigate the effect of tert-butylhydroquinone (tBHQ) on scrotal heat-induced damage in mice testes, 8-week-old mice were divided into 6 groups and administered with or without tBHQ through diet (10 mg/g), intraperitoneal injection (100 mg/kg body weight), or intratestis injection (12.5 mg/kg body weight), respectively. After single scrotal heat exposure (42 °C for 25 min), trunk blood and testes were collected 48 h later. The testes from diet and intraperitoneal tBHQ-treated mice showed more compact interstitial cells and less germ cell loss in the seminiferous epithelium compared with their corresponding non-tBHQ groups. However, intratestis tBHQ treatment showed no marked difference relative to the non-treatment group. In addition, pre-treatment of tBHQ caused lower testosterone concentrations and reduced expression of cytochrome P450 17α-hydroxylase/17,20-lyase (CYP 17) compared to the corresponding non-tBHQ groups. The results indicated that scrotal heat-induced structural damage was partly prevented by pre-treatment of tBHQ, which could be used as an effective antioxidant for preventing scrotal heat-mediated male infertility.
Assuntos
Antioxidantes/farmacologia , Temperatura Alta/efeitos adversos , Hidroquinonas/farmacologia , Infertilidade Masculina/prevenção & controle , Testículo/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Hidroquinonas/uso terapêutico , Infertilidade Masculina/etiologia , Masculino , Camundongos , Espermatozoides/efeitos dos fármacos , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/metabolismo , Testículo/patologia , Testosterona/sangueRESUMO
MicroRNAs (miRNAs) are an important class of small noncoding RNAs that are highly conserved in plants and animals. Many miRNAs are known to mediate a myriad of cell processes, including proliferation and differentiation, via the regulation of some transcription and signaling factors, which are closely related to muscle development and disease. In this study, small RNA cDNA libraries of Boer goats were constructed. In addition, we obtained the goat muscle miRNAs by using Solexa deep-sequencing technology and analyzed these miRNA characteristics by combining it with the bioinformatics technology. Based on Solexa sequencing and bioinformatics analysis, 562 species-conserved and 5 goat genome-specific miRNAs were identified, 322 of which exceeded 100 in the expression levels. The results of real-time quantitative polymerase chain reaction from 8 randomly selected miRNAs showed that the 8 miRNAs were expressed in goat muscle, and the expression patterns were consistent with the Solexa sequencing results. The identification and characterization of miRNAs in goat muscle provide important information on the role of miRNA regulation in muscle growth and development. These data will help to facilitate studies on the regulatory roles played by miRNAs during goat growth and development.
Assuntos
Cabras/genética , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/genética , Desenvolvimento Muscular/genética , Animais , Sequência de Bases , Biologia Computacional/métodos , Sequência Conservada , Perfilação da Expressão Gênica , Biblioteca Gênica , Cabras/fisiologia , MicroRNAs/metabolismo , Dados de Sequência Molecular , Análise de Sequência de RNARESUMO
A novel dimeric dihydrochalcone, verbenachalcone (1), was isolated from the aerial parts of Verbena littoralis. Its structure was elucidated, on the basis of spectral data interpretation, as 4,2',4',2' ",4' "-pentahydroxy-3' '-methoxy-3-O-4' '-tetrahydrobichalcone. This compound caused a significant enhancement of nerve growth factor-mediated neurite outgrowth from PC12D cells.