miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010

<p>Abstract</p> <p>Background</p> <p>In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.</p> <p>Methods</p> <p>Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software.</p> <p>Results</p> <p>Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (<it>p </it>< 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008.</p> <p>Conclusions</p> <p>HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.</p

Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (&gt;90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival

Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops

Feed-forward loops (FFLs) represent an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs, such as araBAD and araFGH operons and adapts to fluctuating environmental nutrients, thereby enhancing the survivability of E. coli. Although computational simulations have been conducted to explore the potential functionality of FFLs, a comprehensive study on the functions of all structural types on the basis of in vivo data is lacking. Moreover, the regulatory role of CRP-mediated FFLs (CRP-FFLs) remains obscure. We identified 393 CRP-FFLs in E. coli using EcoCyc and RegulonDB. Dose&ndash;response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, which were further divided into five functional groups. The microarray and reported regulatory relationships identified 202 CRP-FFLs that were directly regulated by CRP in these eight types of FFLs. Interestingly, 34% (147/432) of genes were directly regulated by CRP and CRP-regulated TFs, which indicates that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs

Superficial Venous Reflux Intervention Guided by Triggered Angiography Non-Contrast-Enhanced Sequence Magnetic Resonance Imaging: Different QFlow Pattern from Health Controls

(1) Background: To assess the effectiveness of triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) in superficial venous reflux and its difference from health controls. (2) Methods: Thirty patients underwent TRANCE MRI before surgical intervention of their superficial venous reflux of the legs. Ten healthy volunteers were included as a control. (3) Results: TRANCE MRI involves the major tributaries, thus enhances the additional ablations in 20% of patients. QFlow pattern of superficial venous reflux (QFlow GSV/PV MF ratio &gt; 1) was compared with the duplex scan (SFJ reflux) using Cohen’s kappa coefficient at 0.967. The 30 morbid legs undergoing TRANCE MRI-guide interventions and the healthy volunteers’ legs on the same side were compared. The stroke volumes (SV) are higher in EIV (p = 0.021) in the left-leg-intervention group. The mean flux (MF) is higher in the EIV (p = 0.012) and trend of increasing in GSV segment (p = 0.087) in the left-leg-intervention group. The QFlow of 10 patients with right leg intervention are higher in GSV in the right-leg-intervention group (SV p = 0.002; FFV p = 0.001; MF p = 0.001). QFlow data is shown for all legs for superficial venous intervention with GSV/PV (MF) ratio &gt; 1. (4) Conclusions: Typical figures in QFlow (GSV/PV MF ratio &gt; 1) could be observed in the morbid limbs but not in the controls

Role of different Salmonella enterica serotypes in THP-1 macrophage-derived foam cell autophagy and inflammatory response

Infected aortic aneurysm is a rare but life-threatening condition. Intimal injury, especially in arteries with atherosclerotic plaques, is vulnerable to Salmonella species. In this study, THP-1 macrophage-derived foam cells were used to mimic the atherosclerotic plaques. We investigated the role of different Salmonella serotype infections in foam cell autophagy and inflammatory response. Three different serotypes of Salmonella enterica-Typhimurium, Enteritidis, and Choleraesuis - with or without a virulence plasmid were used in this study. The foam cell model was established and observed under confocal microscopy. The expression of autophagy and inflammasome-related proteins after Salmonella infection was detected by Western blotting, and the secretion of the proinflammatory cytokines interleukin-1β and IL-18 was detected using ELISA. The plasmid-bearing S. enteritidis OU7130- and plasmid-less S. choleraesuis OU7266-infected foam cells both showed a lower expression of beclin-1 at 0.5 h post-infection (hpi) and p62 at 2 hpi as well as a higher expression of caspase-1 at 2 hpi than other infected cells. Moreover, infection of OU7266 induced the highest IL-1β and IL-18 production among the tested strains. In conclusion, the virulence plasmid of S. enteritidis OU7130 induced foam cell inflammatory responses, whereas that of S. choleraesuis played an opposite role. The different serotype of Salmonella may impact the infected aortic aneurysms through regulating inflammatory balance of the macrophage and foam cells in the atherosclerotic plaque