Exploring the metabolic network of the epidemic pathogen Burkholderia cenocepacia J2315 via genome-scale reconstruction

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia </it>is a threatening nosocomial epidemic pathogen in patients with cystic fibrosis (CF) or a compromised immune system. Its high level of antibiotic resistance is an increasing concern in treatments against its infection. Strain <it>B. cenocepacia </it>J2315 is the most infectious isolate from CF patients. There is a strong demand to reconstruct a genome-scale metabolic network of <it>B. cenocepacia </it>J2315 to systematically analyze its metabolic capabilities and its virulence traits, and to search for potential clinical therapy targets.</p> <p>Results</p> <p>We reconstructed the genome-scale metabolic network of <it>B. cenocepacia </it>J2315. An iterative reconstruction process led to the establishment of a robust model, <it>i</it>KF1028, which accounts for 1,028 genes, 859 internal reactions, and 834 metabolites. The model <it>i</it>KF1028 captures important metabolic capabilities of <it>B. cenocepacia </it>J2315 with a particular focus on the biosyntheses of key metabolic virulence factors to assist in understanding the mechanism of disease infection and identifying potential drug targets. The model was tested through BIOLOG assays. Based on the model, the genome annotation of <it>B. cenocepacia </it>J2315 was refined and 24 genes were properly re-annotated. Gene and enzyme essentiality were analyzed to provide further insights into the genome function and architecture. A total of 45 essential enzymes were identified as potential therapeutic targets.</p> <p>Conclusions</p> <p>As the first genome-scale metabolic network of <it>B. cenocepacia </it>J2315, <it>i</it>KF1028 allows a systematic study of the metabolic properties of <it>B. cenocepacia </it>and its key metabolic virulence factors affecting the CF community. The model can be used as a discovery tool to design novel drugs against diseases caused by this notorious pathogen.</p

Predictors of esophageal varices in patients with HBV-related cirrhosis: a retrospective study

<p>Abstract</p> <p>Background</p> <p>All patients with liver cirrhosis are recommended to undergo an evaluation of esophageal varices (EV) to assess their risk of bleeding. Predicting the presence of EV through non-invasive means may reduce a large number of unnecessary endoscopies. This study was designed to develop a predictive model for varices in patients with Hepatitis B virus-related cirrhosis.</p> <p>Methods</p> <p>The retrospective analysis was performed in 146 patients with Hepatitis B virus-related cirrhosis. The data were assessed by univariate analysis and a multivariate logistic regression analysis. In addition, the receiver operating characteristic curves were also applied to calculate and compare the accuracy of the model and other single parameters for the diagnosis of esophageal varices.</p> <p>Results</p> <p>We found the prevalence of EV in patients with Hepatitis B virus-related cirrhosis to be 74.7%. In addition, platelet count, spleen width, portal vein diameter and platelet count/spleen width ratio were significantly associated with the presence of esophageal varices on univariate analysis. A multivariate analysis revealed that only the spleen width and portal vein diameter were independent risk factors. The area under the receiver operating characteristic curve of regression function (RF) model, which was composed of the spleen width and portal vein diameter, was higher than that of the platelet count. With a cut-off value of 0.3631, the RF model had an excellent sensitivity of 87.2% and an acceptable specificity of 59.5% with an overall accuracy of 80.1%.</p> <p>Conclusion</p> <p>Our data suggest that portal vein diameter and spleen width rather than platelet count may predict the presence of varices in patients with Hepatitis B virus-related cirrhosis, and that the RF model may help physicians to identify patients who would most likely benefit from screenings for EV.</p

Increased Expression of Foxj1 after Traumatic Brain Injury

Foxj1 is a member of the Forkhead/winged-helix (Fox) family of transcription factors, which is required for postnatal differentiation of ependymal cells and a subset of astrocytes in the subventricular zone. The subpopulation of astrocytes has the ability of self-renew and neurogenic potential differentiated into astrocytes, oligodendrocytes, and neurons. However, its expression and function in the central nervous system lesion are not well understood. In this study, we performed a traumatic brain injury (TBI) model in adult rats and investigated the changed expression of Foxj1 in the brain cortex. Western blot and immunohistochemistry analysis showed that the expression of Foxj1 gradually increased, reached a peak at day 3 after TBI, and declined during the following days. Double immunofluorescence staining revealed that Foxj1 was co-expressed with MAP-2 and GFAP. In addition, we detected that Ki67 had the co-localization with NeuN, GFAP, and Foxj1. All our findings suggested that Foxj1 may be involved in the pathophysiology of brain after TBI