Liu H.,Capital Medical University |
Zhang H.,Capital Medical University |
Zhang H.,Peking University |
Wan G.,Capital Medical University |
And 5 more authors.
Journal of Viral Hepatitis | Year: 2014
Summary Acute-on-chronic hepatitis B liver failure (ACHBLF) has a poor prognosis in patients with hepatitis B virus infection. The role of the neutrophil-lymphocyte ratio (NLR), which reflects the inflammatory status of the patient before treatment, has never been studied in this setting. To investigate the predictive value of NLR in patients with ACHBLF, a retrospective cohort with 216 patients and a prospective validation cohort with 73 patients were recruited. Multivariate analyses showed that total bilirubin (TBIL), NLR, age and model for end-stage liver disease (MELD) score had prognostic significance for survival. Both NLR (0.781) and MELD score (0.744) had higher ROC curves, which differed significantly from those for age (0.615) and TBIL (0.691), but not from each other (P = 0.94). NLR ≤2.36 predicted lower mortality (with 91.6% sensitivity and 86.0% negative predictive value), and NLR >6.12 was a warning sign for higher mortality risk (with 90.1% specificity and 80.3% positive predictive value). These results demonstrated that pretreatment NLR was associated with the prognosis of patients with ACHBLF, and elevated NLR predicted poor outcome within 8 weeks. We suggest that NLR cut-offs of ≤2.36 and >6.12 are powerful markers for predicting mortality in ACHBLF. © 2013 John Wiley & Sons Ltd.
Kong Y.,Capital Medical University |
Kong Y.,Beijing Key Laboratory of Emerging Infectious Diseases |
Wang H.,Peking University |
Wang S.,Peking University |
Tang N.,Peking University
Inflammation | Year: 2014
FTY720 is a novel immunosuppressant that modulates sphingosine 1-phosphate (S1P) receptors for the treatment of several diseases. Several hallmarks of liver fibrosis are influenced by S1P, and the interference of S1P signaling by treatment with FTY720 results in beneficial effects in various animal models of fibrosis. However, whether these treatment strategies suppress liver fibrosis progression is incompletely understood. Here, we investigated the effects and mechanisms by which FTY720 improves liver fibrosis in the carbon tetrachloride (CCl4)-induced mouse model. FTY720 treatment significantly attenuated the expression of fibrotic markers in the injured liver of both wild-type and SCID-beige mice. The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to circulation, and subsequently the injured liver, was suppressed by FTY720. Furthermore, in vitro, phosphorylated-FTY720 blocked the migration of BMSCs mediated by S1P. Thus, FTY720 is an effective therapy for liver fibrosis via the suppression of BMSC migration in the CCl4-induced mouse model. © 2014 Springer Science+Business Media.
PubMed | Peking University, Chinese National Institute for Communicable Disease Control and Prevention and Beijing Key Laboratory of Emerging Infectious Diseases
Type: | Journal: Scientific reports | Year: 2016
Bacterial vaginosis (BV) is a highly prevalent disease in women, and increases the risk of pelvic inflammatory disease. It has been given wide attention because of the high recurrence rate. Traditional diagnostic methods based on microscope providing limited information on the vaginal microbiota increase the difficulty in tracing the development of the disease in bacteria resistance condition. In this study, we used deep-sequencing technology to observe dynamic variation of the vaginal microbiota at three major time points during treatment, at D0 (before treatment), D7 (stop using the antibiotics) and D30 (the 30-day follow-up visit). Sixty-five patients with BV were enrolled (48 were cured and 17 were not cured), and their bacterial composition of the vaginal microbiota was compared. Interestingly, we identified 9 patients might be recurrence. We also introduced a new measurement point of D7, although its microbiota were significantly inhabited by antibiotic and hard to be observed by traditional method. The vaginal microbiota in deep-sequencing-view present a strong correlation to the final outcome. Thus, coupled with detailed individual bioinformatics analysis and deep-sequencing technology, we may illustrate a more accurate map of vaginal microbial to BV patients, which provide a new opportunity to reduce the rate of recurrence of BV.
Hou X.,Capital Medical University |
Hou X.,Beijing Institute of Heart Lung and Blood Vessel Diseases |
Yang X.,Capital Medical University |
Yang X.,Beijing Institute of Heart Lung and Blood Vessel Diseases |
And 20 more authors.
Critical Care | Year: 2015
Introduction: Differential hypoxia is a pivotal problem in patients with femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) support. Despite recognition of differential hypoxia and attempts to deliver more oxygenated blood to the upper body, the mechanism of differential hypoxia as well as prevention strategies have not been well investigated. Methods: We used a sheep model of acute respiratory failure that was supported with femoral VA ECMO from the inferior vena cava to the femoral artery (IVC-FA), ECMO from the superior vena cava to the FA (SVC-FA), ECMO from the IVC to the carotid artery (IVC-CA) and ECMO with an additional return cannula to the internal jugular vein based on the femoral VA ECMO (FA-IJV). Angiography and blood gas analyses were performed. Results: With IVC-FA, blood oxygen saturation (SO2) of the IVC (83.6 ± 0.8%) was higher than that of the SVC (40.3 ± 1.0%). Oxygen-rich blood was drained back to the ECMO circuit and poorly oxygenated blood in the SVC entered the right atrium (RA). SVC-FA achieved oxygen-rich blood return from the IVC to the RA without shifting the arterial cannulation. Subsequently, SO2 of the SVC and the pulmonary artery increased (70.4 ± 1.0% and 73.4 ± 1.1%, respectively). Compared with IVC-FA, a lesser difference in venous oxygen return and attenuated differential hypoxia were observed with IVC-CA and FA-IJV. Conclusions: Differential venous oxygen return is a key factor in the etiology of differential hypoxia in VA ECMO. With knowledge of this mechanism, we can apply better cannula configurations in clinical practice. © 2015 Hou et al.
Song H.,Institute of Veterinary Immunology |
Song H.,Capital Medical University |
Song H.,Beijing Key Laboratory of Emerging Infectious Diseases |
Song H.,Northwest University, China |
And 15 more authors.
BMC Infectious Diseases | Year: 2013
Background: With concerns about the disastrous health and economic consequences caused by the influenza pandemic, comprehensively understanding the global host response to influenza virus infection is urgent. The role of microRNA (miRNA) has recently been highlighted in pathogen-host interactions. However, the precise role of miRNAs in the pathogenesis of influenza virus infection in humans, especially in critically ill patients is still unclear. Methods: We identified cellular miRNAs involved in the host response to influenza virus infection by performing comprehensive miRNA profiling in peripheral blood mononuclear cells (PBMCs) from critically ill patients with swine-origin influenza pandemic H1N1 (2009) virus infection via miRNA microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays. Receiver operator characteristic (ROC) curve analysis was conducted and area under the ROC curve (AUC) was calculated to evaluate the diagnostic accuracy of severe H1N1 influenza virus infection. Furthermore, an integrative network of miRNA-mediated host-influenza virus protein interactions was constructed by integrating the predicted and validated miRNA-gene interaction data with influenza virus and host-protein-protein interaction information using Cytoscape software. Moreover, several hub genes in the network were selected and validated by qRT-PCR. Results: Forty-one significantly differentially expressed miRNAs were found by miRNA microarray; nine were selected and validated by qRT-PCR. QRT-PCR assay and ROC curve analyses revealed that miR-31, miR-29a and miR-148a all had significant potential diagnostic value for critically ill patients infected with H1N1 influenza virus, which yielded AUC of 0.9510, 0.8951 and 0.8811, respectively. We subsequently constructed an integrative network of miRNA-mediated host-influenza virus protein interactions, wherein we found that miRNAs are involved in regulating important pathways, such as mitogen-activated protein kinase signaling pathway, epidermal growth factor receptor signaling pathway, and Toll-like receptor signaling pathway, during influenza virus infection. Some of differentially expressed miRNAs via in silico analysis targeted mRNAs of several key genes in these pathways. The mRNA expression level of tumor protein T53 and transforming growth factor beta receptor 1 were found significantly reduced in critically ill patients, whereas the expression of Janus kinase 2, caspase 3 apoptosis-related cysteine peptidase, interleukin 10, and myxovirus resistance 1 were extremely increased in critically ill patients. Conclusions: Our data suggest that the dysregulation of miRNAs in the PBMCs of H1N1 critically ill patients can regulate a number of key genes in the major signaling pathways associated with influenza virus infection. These differentially expressed miRNAs could be potential therapeutic targets or biomarkers for severe influenza virus infection. © 2013 Song et al.; licensee BioMed Central Ltd.
Gao L.-L.,Capital Medical University |
Gao L.-L.,Beijing Key Laboratory of Emerging Infectious Diseases |
Li M.,Lanzhou University |
Wang Q.,Capital Medical University |
And 7 more authors.
Journal of Cellular Biochemistry | Year: 2015
Hypertriglyceridemia leads to liver steatosis, cardiovascular disease, and type 2 diabetes. Although HCBP6 (hepatitis C virus core-binding protein 6) was previously shown to be an HCV (hepatitis C virus) core-binding protein, its biological function remains unclear. Here, we demonstrate that HCBP6 negatively regulates intracellular triglyceride (TG) levels in hepatocytes. We found that bidirectional manipulation of hepatocyte HCBP6 expression by knockdown or overexpression results in increased or decreased TG accumulation, respectively. In addition, HCBP6 mRNA and protein levels exhibited significant time- and dose-dependent increases in a cellular model of lipid-overload hepatic steatosis. Furthermore, TG levels are regulated by HCBP6-sterol regulatory element binding protein 1c (SREBP1c)-mediated fatty acid synthase (FASN) expression. We also demonstrate that HCBP6 mRNA and protein expression is inhibited by microRNA-122 (miR-122), and miR-122 overexpression elicited more robust translational repression of luciferase activity driven by the full 3′-UTR of HCBP6. Taken together, our results provide new evidence that miR-122-regulated HCBP6 functions as a sensor protein to maintain intrahepatocyte TG levels. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Fan X.,Capital Medical University |
Fan X.,Beijing Key Laboratory of Emerging Infectious Diseases |
Chuan S.,Capital Medical University |
Chuan S.,Beijing Key Laboratory of Emerging Infectious Diseases |
And 2 more authors.
Inflammation | Year: 2013
It was reported that O glycosylation is associated with hepatic stellate cell activation and regulates collagen expression. In this study, we aimed to investigate the effect of O glycosylation on the activation of human hepatic stellate cells. We found that the inhibitor of O glycosylation, benzyl-α-GalNAc (2 and 4 mM), could significantly inhibit cells proliferation in a dose-dependent manner. Moreover, benzyl-α-GalNAc decreased the expressions of α-smooth muscle actin, collagen I, and collagen III. The results indicate that O glycosylation is involved in the activation of hepatic stellate cells. © 2013 Springer Science+Business Media New York.
He Y.,Capital Medical University |
He Y.,Central South University |
Wang B.,Capital Medical University |
Wang B.,Beijing Key Laboratory of Emerging Infectious Diseases |
And 6 more authors.
Transplantation | Year: 2015
Background. Adoptively transferring different sources of myeloid-derived suppressor cells (MDSCs)may assist in mice corneal transplant survival. Methods. Allogeneic full thickness corneal transplantation (donor C57BL/6 to recipient Balb/c mice) was performed. Naive myeloid cells, inflammation-induced MDSCs (iMDSCs), and tumor-induced MDSCs (tMDSCs) were purified from bone marrow of naive, cecal ligation and puncture, or tumor-bearing Balb/c mice, respectively. The inhibitory abilities of myeloid cells toward CD4+ T cell proliferation were accessed by in vitro carboxyfluorescein diacetate, succinimidyl ester (CFSE) assays.Myeloid cells were adoptively transferred to corneal recipients by retroorbital injection after corneal transplantation. Corneal grafts were examined and photographed for a period of 45 days. The growth of corneal graft neovascularization was quantitatively measured by image editing software. Histopathology was performed to evaluate corneal graft inflammation. Results. The iMDSCs and tMDSCs significantly inhibited T cell proliferation in vitro and significantly prolonged corneal allograft survival in vivo. Strikingly, iMDSC transferring significantly reduced neovascularization that was comparable to transferring of tMDSCs, without additional immunosuppression. However, additional adoptive transfer of MDSCs did not further ameliorate corneal survival in these allogeneic corneal transplantationmice.Conclusions. Inflammation-inducedMDSC transfer could reduce corneal neovascularization and prolong corneal allograft survival. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Ju L.,Capital Medical University |
Zeng H.,Capital Medical University |
Zeng H.,Beijing Key Laboratory of Emerging Infectious Diseases |
Chen Y.,Capital Medical University |
And 4 more authors.
Journal of Neuroscience Research | Year: 2015
Microglia are versatile immune effector cells of the CNS and are sensitive to various stimuli. The different methods used to isolate microglia may affect some of their characteristics, such as their polarization state. The influence of cell sorting methods on the polarization state of microglia has never been studied. Mixed glial culture system (MGCS) and magnetic activated cell sorting (MACS) are two methods that are commonly used to purify microglia. This study compares the immunological states between microglia isolated by MGCS and microglia isolated by MACS. We show that microglia isolated by MGCS exhibit a stronger immune-activated state than microglia isolated by MACS. They present an elevated phagocytic ability and high levels of markers associated with classical activation (M1) and alternative activation (M2). In addition, high levels of M1-type and M2-type chemokine (C-C motif) ligand 2 and transforming growth factor-β1 were detected in the culture medium of mixed glial cells. Our results show that microglia isolated by MGCS are in an immune-activated state, whereas microglia isolated by MACS appear to be closer to their primary in vivo state. Therefore, the immune status of microglia, depending on the protocol used to purify them, should be carefully considered in neuropathology research. © 2015 Wiley Periodicals, Inc.
PubMed | Capital Medical University and Beijing Key Laboratory of Emerging Infectious Diseases
Type: | Journal: Journal of cellular biochemistry | Year: 2017
Liver fibrosis is a reversible wound-healing response to any etiology of chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrogenesis. Generally, persistent activation and proliferation of HSCs results in liver fibrosis progression, while primary mechanisms of liver fibrosis resolution are apoptosis and reversion to a quiescent phenotype of activated HSCs. NS5ATP13 (HCV NS5A-transactivated protein 13) is involved in nucleologenesis and tumorigenesis, but its role in liver fibrosis and HSC activation remains unclear. This study found that NS5ATP13 was upregulated in both fibrotic liver tissues and activated human HSCs induced by TGF-1. Moreover, NS5ATP13 enhanced extracellular matrix (ECM) production and HSC activation, with or without TGF-1 treatment, likely involving the TGF-1/Smad3 signaling pathway. Additionally, NS5ATP13 boosted HSC proliferation by inhibiting cell apoptosis. Furthermore, HCV NS5A promoted the profibrogenic effect of NS5ATP13 partly through TGF-1 and NF-B p65 (RelA) upregulation. Meanwhile, NS5ATP13 was required for the pro-fibrogenic effect of NF-B. Moreover, NS5ATP13 and NF-B phosphorylation as well as HSC activation were reduced by CX-4945, a CK2 specific inhibitor. These findings indicated that NS5ATP13 acts as a profibrogenic factor, providing a potential target for antifibrotic therapies. This article is protected by copyright. All rights reserved.