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BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.
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INTRODUCTION: The prevalence of frailty defined by FRAIL-NH varies among different studies in nursing homes, ranging from 19.0% to 75.6%. This study investigated the prevalence of frailty in a nursing home in Taiwan using different diagnostic criteria for frailty. METHODS: The 7-item FRAIL-NH scale was used for assessing frailty. There are 7 components: fatigue, resistance, mobility, incontinence or disease, weight loss, eating style and assistance with dressing. Each item is worth 0, 1, or 2 points for a total score of 14 points. We sorted and summarized the patients, according to the number of variables, into the not frail, frail, and most frail groups. Descriptive analysis was applied to understand the basic attributes of the elderly with different degrees of frailty, the influencing factors of frailty, and the occurrence of frailty. RESULTS: Our final sample included 34 residents. They were aged between 56 and 100 years (mean age 83.91 ± 10.84), and 18 (52.94%) were female. The frail group revealed a higher prevalence of males than of females. The marital status composition of participants was as follows: 2 (5.88%) unmarried, 24 (70.59%) married, and 8 (23.53%) widowed. The mean FRAIL-NH score was 5.79±3.72. CONCLUSIONS: A significant prevalence of frailty defined by FRAIL-NH was observed in a nursing home in Taiwan. Our findings indicate that frailty is an important issue in nursing homes. Further prospective cohort studies using FRAIL-NH evaluation are warranted.
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Fragilidade/epidemiologia , Casas de Saúde/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , TaiwanRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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A single random oligonucleotide 3H primer has been previously applied in random-amplified- polymorphic-DNA (RAPD)-PCR to distinguish stocked bacteria E. coli within a cocktail mixture also containing Enterococcus faecalis, Bifidobacterium longum and Ruminococcus gnavus. In this study, we demonstrate that a 702 base pair (bp) gene fragment can be amplified as a unique pattern by RAPD-PCR using a 3H primer in human faeces containing E. coli. This unique 702 bp amplicon contained a 687 bp gene fragment identified as the C-terminal region of the glutamate-ammonia-ligase adenyltransferase (glnE) gene of E. coli. By high-resolution melt (HRM) analysis, a mean melt-curve temperature of this 702 bp amplicon was determined to be approximately 88.1 ± 0.22 degrees Celsius (°C). A combination of RAPD with HRM in one single reaction based on this amplicon can achieve semi-quantitative detection of up to 102 CFU/ml of E. coli. To increase the signal intensity of HRM, a primer pair capable of screening E. coli directly from fresh human faeces was re-designed from the 687 bp gene segment, giving a mean peak melt-curve temperature at 88.35 ± 0.11 °C. Finally, single-nucleotide polymorphisms of this 687 bp gene segment were analysed for pathogenic E. coli strains, including UMN026, O83:H1, O104:H4, O157:H7 and O169:H41. We conclude that this 687 bp segment of the glnE gene has a high potential for screening of human faecal E. coli, including pathogenic strains, in contaminated food and water.
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Primers do DNA/metabolismo , Escherichia coli/enzimologia , Escherichia coli/genética , Genes Bacterianos , Glutamato-Amônia Ligase/química , Glutamato-Amônia Ligase/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico , Sequência de Aminoácidos , Pareamento de Bases/genética , Sequência de Bases , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Glutamato-Amônia Ligase/metabolismo , Humanos , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
OBJECTIVE: To explore the effect of long non-coding ribonucleic acid (lncRNA) H19 on the apoptosis of vascular endothelial cells in arteriosclerosis obliterans (ASO) via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. PATIENTS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured, and lncRNA H19 was inhibited by Si-H9 and overexpressed by H19-OE. Then, the apoptosis rate was detected by flow cytometry, the target of lncRNA H19 was detected by dual luciferase reporter gene assay, and changes in the protein level were determined via Western blotting (WB). RESULTS: LncRNA H19 exhibited high expression in serum of patients with ASO, and compared with that in congeneric normal mice, the expression of lncRNA H19 in ASO mice rose. Besides, the proliferation ability of cells transfected with H19-OE was markedly strengthened, and H19-OE treatment could down-regulate the expression level of the apoptin, active cysteinyl aspartate-specific proteinase-3 (Caspase-3). In addition, lncRNA H19 bound to micro ribonucleic acid (miR)-19a in a targeted way. After lncRNA H19 was overexpressed, the expression of the NF-κB pathway key factors, p38 and p65, were notably increased, and the nuclear translocation of p65 was significantly enhanced after transfection with miR-19a. CONCLUSIONS: LncRNA H19 promotes the proliferation of vascular endothelial cells in ASO and inhibits the apoptosis of them via the NF-κB pathway.
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Apoptose/genética , Arteriosclerose Obliterante/genética , Arteriosclerose Obliterante/patologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , RNA Longo não Codificante/genética , Animais , Arteriosclerose Obliterante/metabolismo , Caspase 3/biossíntese , Caspase 3/genética , Proliferação de Células , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/biossíntese , Fator de Transcrição RelA/biossíntese , Fator de Transcrição RelA/genética , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaAssuntos
Axila/patologia , Cisto Epidérmico/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Heat shock proteins (HSPs) participate in diverse physiological processes in insects, and HSP70 is one of the most highly conserved proteins in the HSP family. In this study, full-length cDNAs of three HSP70 genes (Lthsc70, Lthsp701, and Lthsp702) were cloned and characterized from Liriomyza trifolii, an important invasive pest of vegetable crops and horticultural crops worldwide. These three HSP70s exhibited signature sequences and motifs that are typical of the HSP70 family. The expression patterns of the three Lthsp70s during temperature stress and in different insect development stages were studied by real-time quantitative PCR. Lthsp701 was strongly induced by high- and low-temperature stress, but Lthsc70 and Lthsp702 were not very sensitive to temperature changes. All three Lthsp70s were expressed during insect development stages, but the expression patterns were quite different. The expression of Lthsc70 and Lthsp702 showed significant differences in expression during leafminer development; Lthsc70 was most highly expressed in female adults, whereas Lthsp702 was abundantly expressed in larvae and prepupae. Lthsp701 expression was not significantly different among leafminer stages. These results suggest that functional differentiation within the LtHSP70 subfamily has occurred in response to thermal stress and insect development.
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Dípteros/genética , Proteínas de Choque Térmico HSP70/genética , Animais , Dípteros/crescimento & desenvolvimento , Dípteros/metabolismo , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Temperatura Alta , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Masculino , Estresse FisiológicoRESUMO
Essentials Disabled-2 (Dab2) phosphorylation status in thrombin signaling of human platelet was investigated. Ser723 was the major Dab2 phosphorylation site in human platelets stimulated by thrombin. Dab2 S723 phosphorylation (pS723) caused the dissociation of Dab2-CIN85 protein complex. Dab2-pS723 regulated ADP release and integrin αIIbß3 activation in thrombin-treated platelets. SUMMARY: Background Disabled-2 (Dab2) is a platelet protein that is functionally involved in thrombin signaling in mice. It is unknown whether or not Dab2 undergoes phosphorylation during human platelet activation. Objectives To investigate the phosphorylation status of Dab2 and its functional consequences in thrombin-stimulated human platelets. Methods Dab2 was immunoprecipitated from resting and thrombin-stimulated platelet lysates for differential isotopic labeling. After enrichment of the phosphopeptides, the phosphorylation sites were analyzed by mass spectrometry. The corresponding phospho-specific antibody was generated. The protein kinases responsible for and the functional significance of Dab2 phosphorylation were defined by the use of signaling pathway inhibitors/activators, protein kinase assays, and various molecular approaches. Results Dab2 was phosphorylated at Ser227, Ser394, Ser401 and Ser723 in thrombin-stimulated platelets, with Ser723 phosphorylation being the most significantly increased by thrombin. Dab2 was phosphorylated by protein kinase C at Ser723 in a Gαq -dependent manner. ADP released from the stimulated platelets further activated the Gßγ -dependent pathway to sustain Ser723 phosphorylation. The Cbl-interacting protein of 85 kDa (CIN85) bound to Dab2 at a motif adjacent to Ser723 in resting platelets. The consequence of Ser723 phosphorylation was the dissociation of CIN85 from the Dab2-CIN85 complex. These molecular events led to increases in fibrinogen binding and platelet aggregation in thrombin-stimulated platelets by regulating αIIb ß3 activation and ADP release. Conclusions Dab2 Ser723 phosphorylation is a key molecular event in thrombin-stimulated inside-out signaling and platelet activation, contributing to a new function of Dab2 in thrombin signaling.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Plaquetas/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Trombina/farmacologia , Proteínas Supressoras de Tumor/metabolismo , Proteínas Reguladoras de Apoptose , Plaquetas/metabolismo , Fibrinogênio/metabolismo , Células HEK293 , Humanos , Fosforilação , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteína Quinase C/metabolismo , Serina , Fatores de TempoRESUMO
This corrects the article DOI: 10.1038/onc.2015.168.
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OBJECTIVE: To investigate the effects of folic acid combined with vitamin B12 on deep vein thrombosis (DVT) in patients with homocysteine cerebral infarction. PATIENTS AND METHODS: 90 patients with homocysteine cerebral infarction with DVT that were admitted to our hospital from January to July 2015 were selected as study subjects. They were divided into 2 groups randomly, the treatment group (n=45) and the non-treatment group (n=45). The treatment group was administered folic acid and vitamin B12, while the non-treatment group wasn't administered folic acid and vitamin B12. We compared and analyzed the levels of Hcy, folic acid and vitamin B12 of both groups. We investigated the correlation between the groups of patients with Hcy and folic acid and vitamin B12 treatment. We performed a comparative analysis of both groups of patients with an anticoagulant international normalized ratio (INR). The INR was recorded in detail for the first time as standard time, stable value time, obtain stable INR value time, activated partial thromboplastin time (APTT) and Prothrombin Time (PT) by color Doppler ultrasound observation of both groups with recurrent thrombosis. RESULTS: We compared results of the intervention and treatment groups, and the prognosis of Hcy decreased significantly (p<0.05). While in the treatment group, folic acid and vitamin B12 levels increased significantly (p<0.05), the non-treatment difference of Hcy, folic acid, and vitamin B12 levels, before and after the patients in the intervention group, were not statistically significant (p>0.05). In the treatment group, Hcy was negatively correlated with folic acid (r=-0.376, p<0.05) while the Hcy of the treatment group was negatively correlated with vitamin B12 (r=-0.583, p<0.05). The intervention treatment group INR first standard time, stable value time and stable INR values were higher than those of non-treatment group (p<0.05). The treatment group APTT average was lower than in the non-treatment group (p<0.05). The average Pt in the treatment group was lower than non-treatment group (p<0.05). In the treatment group, lower limb deep static vein thrombosis recurrence rate was 4.4%, which was lower than the non-treatment group where the lower limb deep vein thrombosis recurrence rate was 28.9% (p<0.05). CONCLUSIONS: Hcy is negatively correlated to folic acid and vitamin B12. Folic acid and vitamin B12 can reduce the recurrence rate of thrombosis in patients with lower extremity deep venous thrombosis in patients with Hcy disease. The mechanism of action may be to prevent the recurrence of thrombosis by reducing the levels of Hcy.
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Infarto Cerebral/tratamento farmacológico , Ácido Fólico/uso terapêutico , Homocisteína/sangue , Trombose Venosa/prevenção & controle , Vitamina B 12/uso terapêutico , Adulto , Idoso , Infarto Cerebral/sangue , Infarto Cerebral/complicações , Quimioterapia Combinada , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Recidiva , Trombose Venosa/sangue , Trombose Venosa/etiologia , Vitamina B 12/administração & dosagem , Vitamina B 12/sangueRESUMO
Heat-shock protein 5 (HSPA5) is a marker for poor prognosis in breast cancer patients and has an important role in cancer progression, including promoting drug resistance and metastasis. In this study, we identify that the specific lysine residue 447 (K447) of HSPA5 could be modified with polyubiquitin for subsequent degradation through the ubiquitin proteasomal system, leading to the suppression of cell migration and invasion of breast cancer. We further found that GP78, an E3 ubiquitin ligase, interacted with the C-terminal region of HSPA5 and mediated HSPA5 ubiquitination and degradation. Knock down of GP78 significantly increased the expression of HSPA5 and enhanced migration/invasive ability of breast cancer cells. Knock down of histone deacetylase-6 (HDAC6) increased the acetylation of HSPA5 at lysine residues 353 (K353) and reduced GP78-mediated ubiquitination of HSPA5 at K447 and then increased cell migration/invasion. In addition, we demonstrate that E3 ubiquitin ligase GP78 preferentially binds to deacetylated HSPA5. Notably, the expression levels of GP78 inversely correlated with HSPA5 levels in breast cancer patients. Patients with low GP78 expression significantly correlated with invasiveness of breast cancer, advanced tumor stages and poor clinical outcome. Taken together, our results provide new mechanistic insights into the understanding that deacetylation of HSPA5 by HDAC6 facilitates GP78-mediated HSPA5 ubiquitination and suggest that post-translational regulation of HSPA5 protein is critical for HSPA5-mediated metastatic properties of breast cancer.
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Neoplasias da Mama/metabolismo , Proteínas de Choque Térmico/metabolismo , Histona Desacetilases/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Chaperona BiP do Retículo Endoplasmático , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Desacetilase 6 de Histona , Histona Desacetilases/genética , Humanos , Camundongos SCID , Dados de Sequência Molecular , Invasividade Neoplásica , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma/metabolismo , Homologia de Sequência de Aminoácidos , UbiquitinaçãoRESUMO
MicroRNAs (miRNAs) are small RNAs that suppress gene expression by their interaction with 3'untranslated region of specific target mRNAs. Although the dysregulation of miRNAs has been identified in human cancer, only a few of these miRNAs have been functionally documented in breast cancer. Thus, defining the important miRNA and functional target involved in chemoresistance is an urgent need for human breast cancer treatment. In this study, we, for the first time, identified a key role of miRNA 520h (miR-520h) in drug resistance. Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPK2) expression, as restoring DAPK2 abolished miR-520h-promoted drug resistance, and knockdown of DAPK2 mitigated cell death caused by the depletion of miR-520h. Furthermore, we observed that higher level of miR-520h is associated with poor prognosis and lymph node metastasis in human breast cancer patients. These results show that miR-520h is not only an independent prognostic factor, but is also a potential functional target for future applications in cancer therapeutics.
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Neoplasias da Mama/genética , Proteínas Quinases Associadas com Morte Celular/biossíntese , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/biossíntese , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proteínas Quinases Associadas com Morte Celular/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/genética , Paclitaxel/administração & dosagem , RNA Mensageiro/biossínteseRESUMO
While Liriomyza sativae (Diptera: Agromyzidae), an important invasive pest of ornamentals and vegetables has been found in China for the past two decades, few studies have focused on its genetics or route of invasive. In this study, we collected 288 L. sativae individuals across 12 provinces to explore its population genetic structure and migration patterns in China using seven microsatellites. We found relatively low levels of genetic diversity but moderate population genetic structure (0.05 < F ST < 0.15) in L. sativae from China. All populations deviated significantly from the Hardy-Weinberg equilibrium due to heterozygote deficiency. Molecular variance analysis revealed that more than 89% of variation was among samples within populations. A UPGMA dendrogram revealed that SH and GXNN populations formed one cluster separate from the other populations, which is in accordance with STRUCTURE and GENELAND analyses. A Mantel test indicated that genetic distance was not correlated to geographic distance (r = -0.0814, P = 0.7610), coupled with high levels of gene flow (M = 40.1-817.7), suggesting a possible anthropogenic influence on the spread of L. sativae in China and on the effect of hosts. The trend of asymmetrical gene flow was from southern to northern populations in general and did not exhibit a Bridgehead effect during the course of invasion, as can be seen by the low genetic diversity of southern populations.
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Migração Animal , Dípteros/fisiologia , Variação Genética , Animais , China , Dípteros/genética , Fluxo Gênico , Repetições de Microssatélites/genéticaRESUMO
Gamma time-frequency responses (TFRs) induced by painful laser in the contralateral primary somatosensory (SI) cortex have been shown to correlate with perceived pain-intensity in human. Given the functional roles of gamma TFRs in the cortical spaces, it remains unclear whether such a relationship is sustained for other brain regions where the laser-evoked potentials (LEPs) are presented. In this study, we delivered the painful laser pluses at random pain-intensity levels (i.e. strong, medium and weak) in a single train to the dorsal hand of six patients with uncontrolled epilepsy. The laser stimulus produced a painful pinprick sensation by activating nociceptors located in the superficial layers of the skin. For each patient, arrays of >64 subdural electrodes were implanted directly covering the contralateral SI, parasylvian (PS) and medial frontal (MF) cortices to study the stimulus related gamma (TFRs) in the neocortex. In addition, using the same stimulation paradigm, the modality specificity of gamma TFRs was further examined by applying innocuous vibrotactile stimuli to the same regions of the dorsal hand in a separated group of five patients. Our results showed that gamma TFRs are not modality specific, but the largest gamma TFRs were consistently found within the SI region and noxious laser elicited significantly stronger gamma TFRs than innocuous nonpainful vibratory stimuli. Furthermore, stronger pain induced stronger gamma TFRs in the cortices of SI (r=0.4, p<0.001) and PS (r=0.29, p=0.005). Given that potentially harmful noxious stimulus would automatically capture greater attention than the innocuous ones, our results support the hypothesis that the degree of SI and PS gamma TFRs is associated with an attentional drive provoked by painful stimuli.
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Encéfalo/fisiologia , Ritmo Gama , Nociceptividade/fisiologia , Percepção do Tato/fisiologia , Adolescente , Adulto , Epilepsia/fisiopatologia , Potenciais Somatossensoriais Evocados , Feminino , Lobo Frontal/fisiologia , Mãos , Humanos , Lasers , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estimulação Física , Córtex Somatossensorial/fisiologia , Lobo Temporal/fisiologia , Adulto JovemRESUMO
Hepatitis B virus (HBV) infection is a major health problem worldwide. This virus and its hosts are often fated to continual co-evolutionary interactions. Codon usage analysis has significance for studies of co-evolution between viruses, their hosts, and mRNA translation. Adaptation of the overall codon usage pattern of HBV to that of humans is estimated using the synonymous codon usage value (RSCU), and the synonymous codon usage biases for the translation initiation region (TIR) of HBV are analyzed by calculation of the usage fluctuation of each synonymous codon along the TIR (the first 50 codon sites of the whole coding sequence of HBV). With respect to synonymous codon usage, our results demonstrated that HBV had no significant tendency to select over-represented codons, but had a significant tendency to select certain under-represented codons in the viral genome. Within the three common HBV hosts, 14 of 59 codons had a similar usage pattern, suggesting that mutation pressure from this DNA virus played an important role in the formation of virus synonymous codon usage. In addition, there was no obvious trend for the codons with relatively low energy to be highly selected in the TIR of HBV, suggesting that the synonymous codon usage patterns for the TIR might not be affected by the nucleotide sequence secondary structure; however, synonymous codon usage in the TIR of HBV was influenced by the overall codon usage patterns of the hosts to some degree. Our results suggest that mutation pressure from HBV plays an important role in the formation of synonymous codon usage of the viral genome, while translation selection from the hosts contributes to virus translational fine-tuning.
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Códon , Vírus da Hepatite B/genética , Iniciação Traducional da Cadeia Peptídica , Sequência de Bases , Evolução Biológica , Evolução Molecular , Genoma Viral , Interações Hospedeiro-Patógeno , Humanos , Mutação , Fases de Leitura Aberta , Mutação SilenciosaRESUMO
Several studies suggest that Wnt signaling contributes to reprogramming and maintenance of cancer stem cell (CSC) states activated by loss of membranous E-cadherin expression. However, E-cadherin's exact role in Wnt/ß-catenin-mediated promotion of the CSC phenotype remains unclear. Recently, a significant positive correlation has been observed between the expression of nuclear (an aberrant nuclear localization) E-cadherin and ß-catenin in gastric and colorectal carcinomas. Here we conducted a series of in-vitro and in-vivo studies to show that the ß-catenin/TCF4 interaction was abolished by E-cadherin and was correlated with its nuclear localization, and consequently decreased ß-catenin/TCF4 transcriptional activity. Nuclear E-cadherin was a negative regulator of Wnt/ß-Catenin-elicited promotion of the CSC phenotype. Using immunohistochemistry on lung cancer tissue microarrays, we found that changes in subcellular location of E-cadherin may be described by tumor grade and stage, suggesting cellular redistribution during lung tumorigenesis. Furthermore, nuclear E-cadherin expression was more significantly inversely correlated with CD133 (a lung CSC marker) expression (P<0.005) than total E-cadherin expression (P<0.05), suggesting that lung cancer as defined by nuclear E-cadherin(Low)/nuclear ß-catenin(High)/CD133(High) biomarkers has superior prognostic value over total E-cadherin(Low)/nuclear ß-catenin(High)/CD133(High).
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INTRODUCTION: A variety of inflammatory disorders influence the serum white blood cell (WBC) count. Elevated systemic inflammatory insult may contribute to impaired lung function, such as obstructive or restrictive lung disease. The aim of our study is to investigate the correlation between WBC count and pulmonary function. MATERIAL AND METHODS: Eligible participants aged ≥18âyears (n=16 312) were enrolled from the United States National Health and Nutrition Examination Survey III, 1988-1994. Pertinent information including pulmonary function test, demographics, WBC count, glucose, C-reactive protein and a personal health questionnaire were obtained for subjects without known pulmonary diseases. White blood cell counts were classified into quartiles over the normal range. Multiple hierarchical regression models and trends testing were used to assess the correlation between WBC counts and pulmonary function tests. RESULTS: In the unadjusted mode of quartile-based analysis, the beta coefficients interpreted as the differences in FEV1% predicted upon comparing subjects in the upper three quartiles of WBC count to those in the lowest quartile were -0.007, -0.022 and -0.041 (P<0.001). After adjusting for multiple pertinent covariates, inverse association between quartiles of WBC count and FEV1% predicted remained essentially unchanged. The negative trends between FEV1% predicted and WBC count quartiles in the stratified comparison with extended-model approach were statistically significant (P for trends<0.001) in quartile-based multiple linear regression. CONCLUSIONS: Elevated WBC count is independently associated with declined pulmonary function. It may be a simple, accessible and inexpensive indicator of changes in pulmonary function.
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Volume Expiratório Forçado/imunologia , Adulto , Idoso , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Inquéritos NutricionaisRESUMO
Hand, foot, and mouth disease (HFMD) is a systemic illness in children and is usually caused by enterovirus 71 (EV71). To provide new insights into the genetic features of EV71 and the relationship between the overall codon usage pattern of this virus and that of humans, values for relative synonymous codon usage (RSCU), effective number of codons (ENC), codon adaptation index (CAI), and nucleotide composition were calculated and analyzed. The relationship between ENC values and (G+C)3% suggests that, although nucleotide composition plays an important role in shaping the overall codon usage pattern of this virus, other factors also affect this pattern. In addition, the negative correlation between the CAI value and (G+C)3% suggests that the secondary structure of the EV71 coding sequence caused by its nucleotide composition can affect gene expression. Moreover, there was no significant correlation between ENC and CAI, suggesting that gene expression does not play a role in shaping the overall codon usage pattern of EV71. The overall codon usage pattern of the EV71 virus is only partly similar to the general codon pattern of human, suggesting that, although EV71 has co-evolved with humans for extended periods, mutation pressure played an important role in shaping the virus's overall codon usage pattern. These results revealed that the EV71 virus has developed a subtle strategy during evolution for adapting to environmental changes in its host cells solely by means of mutation pressure.
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Códon/genética , DNA Viral/genética , Enterovirus Humano A/genética , Composição de Bases , DNA Viral/química , Enterovirus Humano A/química , Evolução Molecular , Mutação , Conformação de Ácido NucleicoRESUMO
OBJECTIVE: To evaluate the diagnostic performance of gadoxetic acid-enhanced MRI with an emphasis on the usefulness of the hepatobiliary phase (HBP) in T-staging of gallbladder carcinoma. METHODS: 66 patients with surgically confirmed gallbladder carcinoma underwent MRI. Two radiologists independently reviewed two sets of gadoxetic acid-enhanced MRI without and with the HBP. Local tumour spread was evaluated according to T-staging, and the results were compared with pathological findings. The diagnostic performance of two image sets to differentiate each T-stage was compared. RESULTS: The sensitivities of MRI with the HBP to differentiate T1 vs ≥ T2 lesions, ≤ T2 vs ≥ T3 lesions and ≤ T3 vs T4 lesions were 96.3%, 85.7% and 100% for Observer 1 and 92.6%, 95.2% and 100% for Observer 2, respectively (p<0.0001). By adding the HBP, the sensitivities to differentiate ≤ T2 vs ≥ T3 lesions were increased from 66.7% to 85.7% for Observer 1 and from 81.0% to 95.2% for Observer 2, although there was no significant difference (p>0.05). The overall accuracies for T-staging were increased from 80.3% to 86.4% for Observer 1, a statistically significant degree (p=0.046), and from 83.8% to 87.9% for Observer 2 (p>0.05). The k-value for the two observers indicated excellent agreement. CONCLUSION: Gadoxetic acid-enhanced MRI provided acceptable diagnostic performance for T-staging of gallbladder carcinoma. Addition of the HBP aids in the detection of liver invasion. ADVANCES IN KNOWLEDGE: In the T-staging of gallbladder carcinoma, gadoxetic acid-enhanced MRI with the HBP may enhance detection of liver invasion.