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The aim of this study was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on the peripheral blood microRNAs (miRNAs) of patients with type 2 diabetes mellitus (T2DM). miRNAs are small 20- to 22-nucleotide (nt) noncoding RNAs. They constitute a novel class of gene regulators that negatively regulate gene expression at the post-transcriptional level. miRNAs play an important role in several biological processes. Twelve patients with T2DM who were scheduled to undergo laparoscopic RYGB surgery were separated into two groups, using a body mass index of 30 kg/m2 as a cut-off point. Venous blood was collected before operation and 12 months after operation. A significant change was observed in the peripheral blood miRNA expression profile of both groups after RYGB surgery compared with those before operation. The expression levels of hsa-miR-29a-3p, hsa-miR-122-5p, hsa-miR-124-3p, and hsa-miR-320a were downregulated. The methylation state of the CpG sites within an approximately 400-bp genomic DNA fragment of each of the four miRNA genes, including about 200 bp upstream and 100 bp downstream of the pre-miRNA, did not vary after RYGB surgery. With remission of T2DM in both groups, RYGB could modulate the expression level of many peripheral blood miRNAs associated with lipid metabolism, insulin secretion, beta-cell function, and insulin resistance. The expression level of peripheral blood diabetes-related miRNA varied in patients with T2DM after receiving RYGB surgery, laying a strong foundation for future studies on this subject. The molecular mechanisms underlying RYGB surgery that can cause aberrant expression of miRNA remains to be determined.
Assuntos
Diabetes Mellitus Tipo 2/sangue , MicroRNAs/sangue , Obesidade Mórbida/cirurgia , Adulto , Metilação de DNA , Diabetes Mellitus Tipo 2/complicações , Derivação Gástrica , Humanos , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We investigated the effects of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) on the expression of aquaporin 5 (AQP5) in ischemia/reperfusion (I/R) rats following deep hypothermia cardiac arrest. Wistar rats were randomly divided into: a sham control group (subjected to a sham operation); an I/R group (subjected to occlusion of the bronchial arteries and the left inferior pulmonary artery); an H89 group (subjected to occlusion of the bronchial arteries and the left inferior pulmonary vein and artery, and treated with 5 mg/kg H89 for 2 days before the study); and a forskolin group (subjected to occlusion of the bronchial arteries and the left inferior pulmonary vein and artery, and treated with 5 mg/kg forskolin for 2 days before the study). Expression levels of AQP5 mRNA and protein were determined using reverse transcription-polymerase chain reaction and western blotting. Decreased expression of AQP5 was noted in the pulmonary tissues of the I/R group compared with the sham controls. Compared to that in the control group, there was a notable decrease in AQP5 expression in the I/R group. After treating with forskolin, AQP5 expression increased in the forskolin group compared with the I/R group. In the H89 group, AQP5 expression decreased compared with the I/R group. The decreased expression of AQP5 was possibly associated with acute pulmonary injury induced by I/R. The cAMP-PKA signal pathway may be involved in the expression of AQP5 in I/R rats after deep hypothermia cardiac arrest.
Assuntos
Lesão Pulmonar Aguda/etiologia , Aquaporina 5/genética , Proteínas Quinases Dependentes de AMP Cíclico , Parada Cardíaca/complicações , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/etiologia , Transdução de Sinais , Lesão Pulmonar Aguda/metabolismo , Animais , Modelos Animais de Doenças , Regulação para Baixo , Hipotermia , Isquemia/complicações , Isquemia/etiologia , Pulmão/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismoRESUMO
OBJECTIVE: Indications for resection of hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify prognostic factors that affect overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatectomy. METHODS: From 2004 to 2010, 601 patients with HCC who underwent resection were enrolled. Factors stratified into the host, biochemical, surgical treatment and tumor-related features in terms of recurrence and overall survival were analyzed. Prognostic factors were evaluated by univariate and multivariate analyses, with Kaplan-Meier survival analyses and Cox proportional hazard model. RESULTS: The overall survival rates of 1-, 3- and 5- year were 79, 62, and 54 %, and the corresponding DFS rates were 51, 38 and 31 %, respectively. In a multivariate analysis, Child-Pugh, serum AFP level, ALT level, time for hepatic resection, tumor differentiation, maximum size of tumors, local necrosis, portal vein tumor thrombus, and TNM Stage were correlated significantly with patients' OS. Gender (P = 0.046), cigarette smoking (P = 0.007), serum AFP level (P = 0.001), GGT level (P = 0.002), maximum size of tumors (P = 0.009), liver cirrhosis (P = 0.025), portal vein tumor thrombus (P = 0.022), microvascular tumor thrombus (P = 0.007) and TNM Stage (P = 0.001) were significantly affected DFS. CONCLUSION: Preoperative AFP level, maximum size of tumors, portal vein tumor thrombus and TNM Stage were revealed as important prognostic factors for OS and DFS through follow-up of a relatively large cohort of Chinese HCC patients.
Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto JovemRESUMO
Head and neck cancer (HNC) is one of the most prevalent cancers; it is often diagnosed at its advanced stage and has a low 5-year survival rate. Evidence suggests that noninvasive biomarker microRNAs (miRNAs) are valuable for early diagnosis of HNC. This meta-analysis assessed the diagnostic value of miRNAs in HNC detection. A systematic literature search for relevant studies up to August 4, 2014 was conducted in databases and other sources. Statistical analysis was conducted using STATA 12.0. Pooled sensitivity, specificity, and other parameters, together with a summary receiver operating characteristic curve were used to assess the overall performance of miRNA assays. Subgroup analyses and meta-regression were used to analyze heterogeneity, and a Deeks' funnel plot asymmetry test assessed publication bias. Twenty-four articles with 1856 HNC patients and 1375 controls were included. The pooled results were as follows: sensitivity, 0.80 (95%CI = 0.77-0.83); specificity, 0.80 (95%CI = 0.76-0.85); positive likelihood ratio, 4.1 (95%CI = 3.2-5.2); negative likelihood ratio, 0.25 (95%CI = 0.21-0.30); diagnostic odds ratio (DOR), 16 (95%CI = 11-24); and area under curve (AUC), 0.87 (95%CI = 0.84-0.89). We conducted subgroup analyses based on ethnicity, cancer type, miRNA profiling, and specimen types, and found that miRNA assays yielded the highest accuracy in esophageal cancer. Notably, the DOR was 99 and the AUC was 0.96 for the multiple miRNA test, indicating strong discrimination of cancer patients from healthy people. The meta-analysis indicates that noninvasive miRNAs are a promising diagnostic tool with moderate accuracy for HNC diagnosis.
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Biomarcadores Tumorais/sangue , Neoplasias de Cabeça e Pescoço/sangue , MicroRNAs/sangue , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , MicroRNAs/metabolismoRESUMO
Pathological scar tissues and normal skin tissues were differentiated by screening for differentially expressed genes in pathologic scar tissues via gene expression microarray. The differentially expressed gene data was analyzed by gene ontology and pathway analyses. There were 5001 up- or down-regulated genes in 2-fold differentially expressed genes, 956 up- or down-regulated genes in 5-fold differentially expressed genes, and 114 up- or down-regulated genes in 20-fold differentially expressed genes. Therefore, significant differences were observed in the gene expression in pathological scar tissues and normal foreskin tissues. The development of pathological scar tissues has been correlated to changes in multiple genes and pathways, which are believed to form a dynamic network connection.
Assuntos
Cicatriz/genética , Foliculite/genética , Furunculose/genética , Proteínas/genética , Adulto , Cicatriz/etiologia , Cicatriz/metabolismo , Cicatriz/patologia , Foliculite/complicações , Foliculite/metabolismo , Foliculite/patologia , Prepúcio do Pênis/citologia , Prepúcio do Pênis/metabolismo , Furunculose/complicações , Furunculose/metabolismo , Furunculose/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas/metabolismoRESUMO
We investigated the protective effects of remote postconditioning (RPC) in the lungs of rats with deep hypothermia ischemia/reperfusion (I/R) injury and the role of nuclear factor E2-related factor 2 (Nrf2) signaling in this process. Forty-nine rats were randomly divided into a sham control group, deep hypothermia I/R group, RPC group, I/R+all-trans retinoic acid (ATRA) group, I/R+RPC+ATRA group, I/R+tert-butylhydroquinone (tBHQ) group, and I/R+RPC+tBHQ group. Real-time polymerase chain reaction and Western blot analysis were used to examine Nrf2 mRNA and protein expression, respectively. Compared with the sham control group, Nrf2 expression, malondialdehyde (MDA) content, and the wet/dry weight (W/D) ratio were significantly increased in the I/R group, while superoxide dismutase (SOD) activity was significantly decreased. Pulmonary Nrf2 expression and SOD activity was significantly increased, and MDA content and the W/D ratio were significantly decreased in the RPC group compared with the I/R group. Compared with the I/R group, MDA and W/D ratio significantly decreased and SOD activity remarkably increased in I/R+tBHQ group. After ATRA intervention in the I/R+ATRA group, MDA content and W/D ratio increased and SOD activity decreased compared to the I/R group. MDA content and W/D ratio in the RPC+tBHQ group significantly decreased and SOD activity increased compared with in the RPC group (P < 0.01). In the RPC+ATRA group, MDA content and W/D ratio decreased while SOD activity increased compared with the RPC group (P < 0.01). RPC alleviated deep hypothermia I/R injury; the Nrf2 signaling pathway may be involved in the protective effects induced by RPC.
Assuntos
Hipotermia , Pós-Condicionamento Isquêmico , Fator 2 Relacionado a NF-E2/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Animais , Western Blotting , Pulmão/metabolismo , Pulmão/patologia , Malondialdeído/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Background: Currently, segmentation of healthcare and daily care for the elderly living in nursing homes usually results in the elderly not getting medical treatment timely and effectively. The medical-nursing combined care, which has been put into practice in several areas in China, is developed to enhance the accessibility of healthcare for the elderly. The aim of the study is to explore the effectiveness of the new care service, based on Andersen model, regarding health service utilization, health status and service satisfaction. Methods: The effectiveness of medical-nursing combined care will be measured in a cross-sectional study in nine nursing homes in Jianghan District, Wuhan, China, with 1067 old residents expected to participate. The questionnaire containing items of demographics, health service use, service satisfaction and instrument of SF-36 V2 is developed based on the conceptual framework of Andersen behaviour model of health service utilization. Descriptive analysis, variance analysis, multiple factors analysis, and correlation analysis will be performed to compare the sociological characteristics, health service use, health status and service satisfaction of the elderly living in different modes of nursing homes, to explore the influence factors of care effectiveness, as well as to study the relationship between health behaviour and health outcomes. Conclusion: The study design of analysing the effects of medical-nursing combined care and performing the horizontal comparison among the nursing homes under the framework of Andersen model is blazing new trails. Recruitment and design of questionnaire are important issues. Successful data collection and quality control are also necessary. Taking these into account, this study is estimated to provide evidence for the effectiveness of medical-nursing combined care service in China.
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This study aimed to identify marker genes in diabetic wounds using a dataset based on a DNA microarray of dermal lymphatic endothelial cells, and our results provide a basic understanding of diabetic wounds through further study of these differentially expressed genes (DEGs). From the Gene Expression Omnibus database, we downloaded a gene expression microarray (GSE38396) that includes 8 samples: 4 normal controls and 4 disease samples (type II diabetes). We then identified genes that were differentially expressed between normal and disease samples using packages in R language, constructed a protein-protein interaction (PPI) network and analyzed modules in the network. In addition, phylogenetic analysis was performed by MEGA to find the most conserved genes. Two hundred and thirteen genes were identified as being differentially expressed between normal and disease samples, and we constructed a PPI network that included 213 pairs of proteins. We then identified a module including 20 genes, the function of which was significantly enriched in wounding response. Lastly, the most conserved genes, CD44 and CCL5, were identified through phylogenetic analysis. In summary, we found differentially expressed marker genes, a wounding response-related module, and the most important genes CD44 and CCL5. Our findings suggest new approaches to therapies for diabetic wounds.
Assuntos
Complicações do Diabetes/genética , Perfilação da Expressão Gênica , Transcriptoma , Ferimentos e Lesões/genética , Biomarcadores , Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 2/complicações , Humanos , Filogenia , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Ferimentos e Lesões/metabolismoRESUMO
Human cytomegalovirus (HCMV) genetic determinants of endothelial cell tropism, leukocytes and dendritic cells have been identified in the genes UL131A, UL130, and UL128. We examined the structure of these three genes in HCMV. Eighteen low-passage clinical isolates and five non-passage strains from congenitally HCMV-infected infants in China were used to assess the structures of the UL131A, UL130, and UL128 genes and to find possible relationships between sequence polymorphism and different signs of HCMV disease. Comparisons were made between the UL131A, UL130, and UL128 genes of clinical strains and published sequences of Towne and Merlin strains. The UL131A coding region in the clinical strains was similar to that of Towne and Merlin strains, while UL130, and UL128 coding regions in the clinical strains were parallel with those of Towne and Merlin, respectively. Sequence comparison indicated that the UL130, and UL128 genes encode chemokine-like proteins in the clinical strain; the transmembrane regions of UL131A, and UL130 were conserved in all clinical and reference strains. The three genes of clinical strains from infants with different signs of HCMV disease had similar structure characterization. We conclude that the UL131A, UL130, and UL128 genes are highly conserved in these clinical strains. No correlation was found between the structure of the three genes and variations in HCMV disease. The finding of chemokine-like domains in UL130, and UL128 putative proteins suggests that the predicted products play a role in HCMV infectivity.