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Background: Corynebacterium striatum is a member of the non-diphtherial corynebacteria, which are ubiquitous in nature and generally colonize the skin and mucous membranes of humans. Rarely, it causes infective endocarditis (IE). We report a case of rare left atrial bacterial vegetative mass due to C. striatum masquerading as a myxoma identified through a tortuous diagnostic process, and present a brief review of the relevant literature.Case Presentation: We present a case of 63-year-old man who presented with progressively worsening dyspnea on exertion and lower leg edema, and was diagnosed with heart failure. Transesophageal echocardiography (TEE) revealed that the left atrium was filled with a 2.7 cm × 2.6 cm mass. The patient, who had no signs of infection or related risk factors, was suspected of having a left atrial myxoma clinically. After excising the mass, the histopathology suggested thrombus with no myxocytes. Postoperatively, a fever appeared and C. striatum was isolated from the blood cultures. Although antibiotics were used, the symptoms of heart failure worsened gradually and echocardiography revealed valve vegetation. The patient underwent a second operation because of IE. Surprisingly, the mass was confirmed to be a bacterial vegetation due to C. striatum based on Gram staining at a 1000× magnification, although this was not noted on routine pathological examination of the two surgical specimens.Conclusions: Physicians should be aware of Corynebacterium in blood cultures, which cannot simply be assumed to be a contaminant. A diagnosis of IE should be suspected, particularly in high-risk patients or those with an unexplained fever. Our patient had IE due to C. striatum with no risk factors. This case supports the diagnosis of IE using a combination of pathology and etiology. [ABSTRACT FROM AUTHOR]

Background: The development of techniques for sequencing the messenger RNA (RNA-Seq) enables it to study the biological mechanisms such as alternative splicing and gene expression regulation more deeply and accurately. Most existing methods employ RNA-Seq to quantify the expression levels of already annotated isoforms from the reference genome. However, the current reference genome is very incomplete due to the complexity of the transcriptome which hiders the comprehensive investigation of transcriptome using RNA-Seq. Novel study on isoform inference and estimation purely from RNA-Seq without annotation information is desirable. Results: A Nonnegativity and Sparsity constrained Maximum APosteriori (NSMAP) model has been proposed to estimate the expression levels of isoforms from RNA-Seq data without the annotation information. In contrast to previous methods, NSMAP performs identification of the structures of expressed isoforms and estimation of the expression levels of those expressed isoforms simultaneously, which enables better identification of isoforms. In the simulations parameterized by two real RNA-Seq data sets, more than 77% expressed isoforms are correctly identified and quantified. Then, we apply NSMAP on two RNA-Seq data sets of myelodysplastic syndromes (MDS) samples and one normal sample in order to identify differentially expressed known and novel isoforms in MDS disease. Conclusions: NSMAP provides a good strategy to identify and quantify novel isoforms without the knowledge of annotated reference genome which can further realize the potential of RNA-Seq technique in transcriptome analysis. NSMAP package is freely available at https://sites.google.com/site/nsmapforrnaseq. [ABSTRACT FROM AUTHOR]

Background: Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data. Results: Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG. Conclusions: We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs. [ABSTRACT FROM AUTHOR]

Introduction: The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation. Hepcidin is a β-defensin-like antimicrobial peptide and acts as a principal iron regulatory hormone. Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells. However, nothing is known about its function in lung infectious and inflammatory diseases. We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury.Methods: Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery. Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice. The adenovirus-mediated knockdown of hepcidin in airway epithelial cells was evaluated in vivo. Lung injury and the 7-day survival rate were assessed. The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated.Results: The hepcidin level in airway epithelial cells was upregulated during polymicrobial sepsis. The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased the mortality (53.33% in Ad-shHepc1 treated mice versus 12.5% in Ad-shNeg treated mice, P <0.05). The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages. Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice.Conclusions: Airway epithelial cell-derived hepcidin plays an important role in CLP induced acute lung injury. The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages. [ABSTRACT FROM AUTHOR]

Background: To analyze the clinical characteristics and outcomes of carbapenem-resistant Klebsiella pneumoniae (CRKp) and carbapenem-susceptible K. pneumoniae (CSKp) bloodstream infections (BSIs), and to study the risk factors for development of CRKp BSI and K. pneumoniae BSI-related mortality., Methods: A retrospective case control study of patients with K. pneumoniae BSI was conducted in the intensive care unit of the First Affiliated Hospital, Medical of College, Zhejiang University from January 2013 to December 2014. Carbapenem resistance was defined in accordance with the Clinical and Laboratory Standards Institute 2016 guidelines. Risk factors for the development of CRKp BSI and risk factors for mortality due to K. pneumoniae BSI were assessed. Virulence genes were detected by polymerase chain reaction assay., Results: In total, 48 patients were enrolled in the study, including 31 (65%) patients with CRKp BSI and 17 (35%) patients with CSKp BSI. CSKp infection was associated with more severe clinical symptoms, particularly a higher serum creatinine level (165.06 ± 127.01 in the CSKp group vs. 93.77 ± 84.35 μmol/L in the CRKp group, p =  0.039), but there was no significant difference in prognosis between the CSKp and CRKp groups. On multivariate analysis, indwelling central venous catheter ( p =  0.045) was the only factor independently associated with CRKp bacteremia. However, the mortality of K. pneumoniae BSI patients was not correlated with carbapenem resistance. In addition, the isolates had diverse clonality and different origins. The frequency of detection of the allS and magA virulence genes was higher in the CSKp group than in the CRKp group ( alls p =  0.04; magA p =  0.047)., Conclusions: Patients in the CSKp group experienced more severe clinical symptoms, although mortality did not differ significantly between the CRKp and CSKp groups. An indwelling central venous catheter was the only factor independently associated with CRKp BSI. The mortality of patients with K. pneumoniae BSI was not associated with carbapenem resistance. The frequency of virulence genes was higher in the CSKp group than in the CRKp group.

Background: Corynebacterium striatum is a member of the non-diphtherial corynebacteria, which are ubiquitous in nature and generally colonize the skin and mucous membranes of humans. Rarely, it causes infective endocarditis (IE). We report a case of rare left atrial bacterial vegetative mass due to C. striatum masquerading as a myxoma identified through a tortuous diagnostic process, and present a brief review of the relevant literature., Case Presentation: We present a case of 63-year-old man who presented with progressively worsening dyspnea on exertion and lower leg edema, and was diagnosed with heart failure. Transesophageal echocardiography (TEE) revealed that the left atrium was filled with a 2.7 cm × 2.6 cm mass. The patient, who had no signs of infection or related risk factors, was suspected of having a left atrial myxoma clinically. After excising the mass, the histopathology suggested thrombus with no myxocytes. Postoperatively, a fever appeared and C. striatum was isolated from the blood cultures. Although antibiotics were used, the symptoms of heart failure worsened gradually and echocardiography revealed valve vegetation. The patient underwent a second operation because of IE. Surprisingly, the mass was confirmed to be a bacterial vegetation due to C. striatum based on Gram staining at a 1000× magnification, although this was not noted on routine pathological examination of the two surgical specimens., Conclusions: Physicians should be aware of Corynebacterium in blood cultures, which cannot simply be assumed to be a contaminant. A diagnosis of IE should be suspected, particularly in high-risk patients or those with an unexplained fever. Our patient had IE due to C. striatum with no risk factors. This case supports the diagnosis of IE using a combination of pathology and etiology.

Background: Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated., Methods: The changes of TET family members during TGF-β1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-β1-treated ovarian cancer cells to examine its effect on TGF-β1-induced EMT phenotype. The downstream target of TET3 was further identified. Finally, the relationships of TET3 expression to clinic-pathological parameters of ovarian cancer were investigated with a tissue microarray using immunohistochemistry., Results: TET3 was downregulated during TGF-β1-initiatd epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells. Overexpression of TET3 reversed TGF-β1-induced EMT phenotypes including the expression pattern of molecular markers (E-cadherin, Vimentin, N-cadherin, Snail) and migratory and invasive capabilities of ovarian cancer cells. miR-30d was identified as a downstream target of TET3, and TET3 overexpression resumed the demethylation status in the promoter region of miR-30d precursor gene, resulting in restoration of miR-30d (an EMT suppressor of ovarian cancer cells proven in our previous study) level in TGF-β1-induced EMT. We further found that TET3 expression was decreased in ovarian cancer tissues, especially in serous ovarian cancers. The overall positivity of TET3 was inversely correlated with the grade of differentiation status of ovarian cancer., Conclusion: Our results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-β1-induced EMT.