Feng Xu

Hangzhou Normal University, Hang-hsien, Zhejiang Sheng, China

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Publications (26)49.81 Total impact

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    ABSTRACT: Curcumin has remarkable anti-inflammatory and antioxidant properties. However, its effects on bacterium-induced acute lung injury (ALI) are not fully understood. To investigate the protective effects of curcumin on a mouse model of S. aureus-induced ALI. Mice were pretreated with i.p. injection of curcumin or vehicle 2h before S. aureus instillation. The survival rate and bacterial burden after infection were recorded. Mice were sacrificed for the analyses of severity of pneumonia, integrity of lung barrier, disorder of coagulation cascades and extent of inflammation 12h postinfection. The production of proinflammatory cytokines and chemokines in the lung and bronchoalveolar lavage fluid was detected. Pretreatment with curcumin markedly attenuated S. aureus-induced pneumonia, barrier disruption, lung edema and vascular leakage. Activation of plasminogen activator inhibitor-1 (PAI-1) and infiltration of neutrophils were reduced by curcumin, together with lower levels of proinflammatory cytokines and chemokines. Curcumin can alleviate S. aureus-induced ALI through multiple pathways.
    The Clinical Respiratory Journal 01/2014; · 1.66 Impact Factor
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    ABSTRACT: Macrophage polarization is critical for dictating host defense against pathogens and injurious agents. Dysregulation of macrophage differentiation has been implicated in infectious and inflammatory diseases. Here we show that protein kinase B/Akt1 signaling induced by staphylococcal aureus is essential in shifting macrophages from an antimicrobial phenotype (M1) towards a functionally inert signature. Consistently, mice with Akt1 deletion showed enhanced bacterial clearing and survival advantage over their wild-type littermates. The blunted M1 macrophage reaction driven by Akt1 was associated with decreased RelA/NF-κB activity. Further, microRNA-155 was identified, by repressing expression of suppressor of cytokine signaling (SOCS)1, to promote the transcription of M1 signature genes in Akt1-/- macrophages. Blocking of miR-155 in Akt1-/- macrophages or knockdown of SOCS1 in WT cells respectively disabled or enabled M1 macrophage shift and antibacterial response. These results thus establish an Akt1-mediated, microRNA-involved regulatory circuit which regulates pathogen-driven macrophage polarization and subsequently the host anti-infection response.
    The Journal of Infectious Diseases 04/2013; · 5.85 Impact Factor
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    ABSTRACT: β-elemene, extracted from the ginger plant, possesses antitumor activity against a broad range of cancers clinically. However, the mechanism underlying β-elemene-induced cytotoxicity remains incompletely understood. Here, we show that β-elemene promoted apoptotic cell death in human glioma cells, downregulated survivin gene expression, and induced caspase-9, -3 and -7 activities. Induction of apoptosis was associated with inhibition of survivin gene expression, and restoration of survivin levels remarkably attenuated β-elemene-induced glioma cell death. Moreover, we found that the interaction between surviving and HBXIP, a critical regulator of caspase-9 activity, was impaired by β-elemene treatment. The results, therefore, reveal a caspase-mediated apoptotic pathway induced by β-elemene in human glioma cells, which is associated with downregulation of survivin itself and the interaction between survivin and HBXP.
    Oncology Reports 09/2012; 28(6):2083-90. · 2.30 Impact Factor
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    ABSTRACT: Interferons (IFNs) are cytokines playing an important role in immune responses. Interferons are classified into two distinct types according to specific interferon receptors(IFNR). Type I IFNs include IFN-α and IFN-β, whereas IFN-γ is type II IFN. It is well known that type I IFNs have important roles in the host defense against viruses through activation of interferon receptor A (IFNAR). However, many recent studies have also demonstrated that type I IFNs have effects on immune responses to bacterial infection. This review focuses on the immune regulation of type I IFN-mediated signal pathways in bacterial infections such as listeria monocytogenes, streptococcus, mycobacterium tuberculosis, bacillus anthracis, legionella, pseudomonas aeruginosa and others.
    Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 07/2012; 41(4):464-8.
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    ABSTRACT: Community-acquired pneumonia (CAP) remains one of the leading causes of death from infectious diseases around the world. Most severe CAP patients are admitted to the intensive care unit (ICU), and receive intense treatment. The present study aimed to evaluate the role of the pneumonia severity index (PSI), CURB-65, and sepsis score in the management of hospitalized CAP patients and explore the effect of ICU treatment on prognosis of severe cases. A total of 675 CAP patients hospitalized in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively investigated. The ability of different pneumonia severity scores to predict mortality was compared for effectiveness, while the risk factors associated with 30-day mortality rates and hospital length of stay (LOS) were evaluated. The effect of ICU treatment on the outcomes of severe CAP patients was also investigated. All three scoring systems revealed that the mortality associated with the low-risk or intermediate-risk group was significantly lower than with the high-risk group. As the risk level increased, the frequency of ICU admission rose in tandem and LOS in the hospital was prolonged. The areas under the receiver operating characteristic curve in the prediction of mortality were 0.94, 0.91 and 0.89 for the PSI, CURB-65 and sepsis score, respectively. Compared with the corresponding control groups, the mortality was markedly increased in patients with a history of smoking, prior admission to ICU, respiratory failure, or co-morbidity of heart disease. The differences were also identified in LOS between control groups and patients with ICU treatment, heart, or cerebrovascular disease. Logistic regression analysis showed that age over 65 years, a history of smoking, and respiratory failure were closely related to mortality in the overall CAP cohort, whereas age, ICU admission, respiratory failure, and LOS at home between disease attack and hospital admission were identified as independent risk factors for mortality in the high-risk CAP sub-group. The 30-day mortality of patients who underwent ICU treatment on admission was also higher than for non-ICU treatment, but much lower than for those patients who took ICU treatment subsequent to the failure of non-ICU treatment. Each severity score system, CURB-65, sepsis severity score and especially PSI, was capable of effectively predicting CAP mortality. Delayed ICU admission was related to higher mortality rates in severe CAP patients.
    Chinese medical journal 02/2012; 125(4):639-45. · 0.90 Impact Factor
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    ABSTRACT: Accumulating data suggested that functional expression of Toll-like receptors (TLRs) in tumor cells was involved in tumor progression. Our previous study demonstrated that TLR9 signaling could enhance the tumor progression of human lung cancer cells in vitro and in vivo. We further showed that miR-574-5p was the mostly up-regulated miRNA in human lung cancer cells under TLR9 signaling by miRNA array analysis. Here we characterized the potential role of miRNA-574-5p in enhanced tumor progression induced by TLR9 signaling in human lung cancer. We confirmed that TLR9 signaling effectively elevated the expression of miR-574-5p in human lung cancer cells. Notably, we found that down-regulation of miRNA-574-5p using miR-574-5p inhibitor in vitro or miR-574-5p sponge in vivo significantly abrogated the enhanced tumor progression induced by TLR9 signaling. Further studies showed that miR-574-5p was an important player associated with enhanced tumor progression of human lung cancer cells. Notably, we identified checkpoint suppressor 1 (Ches1) as the dominant direct target for miRNA-574-5p to confer the TLR9 signaling enhanced tumor progression. We revealed that over-expression of Ches1 significantly inhibited the cell cycle entry of human lung cancer cells. Finally, we revealed that the expression of miR-574-5p was positively correlated with TLR9 and reversely correlated with Ches1 in lung cancer patients. Our findings not only facilitated the further understanding of the crosstalk between miRNAs and TLRs in tumor biology, but also provided novel potential candidates for treatment of cancer.
    PLoS ONE 01/2012; 7(11):e48278. · 3.73 Impact Factor
  • Sheng li ke xue jin zhan [Progress in physiology] 10/2011; 42(5):379-82.
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    Yu-sheng Cheng, Feng Xu
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    ABSTRACT: Polyinosinic-polycytidylic acid (polyi:c) is a synthetic analog of double-stranded RNA and an agonist of toll-like receptor (TLR) 3 and retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5). The effect of polyi:c on tumor immunotherapy has been well explored for several decades. The accumulated evidence suggests that polyi:c could be used as a vaccine adjuvant to enhance innate and adaptive immune responses, and to alter the tumor microenvironment. Recent studies have also shown that activation of TLR3 and RLR signaling by polyi:c can directly trigger apoptosis in some cancer cells. This review focuses on polyi:c-induced signaling pathways and the applications of polyi:c in cancer treatment.
    Cancer biology & therapy 12/2010; 10(12):1219-23. · 3.29 Impact Factor
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    ABSTRACT: Although lymph node enlargement is common in active systemic lupus erythematosus (SLE), lymph node examination is frequently ignored in the diagnosis of SLE. Clinical presentation and abnormal laboratory findings are often sufficient for SLE diagnosis, not to mention that the specific histological finding of lymph node necrosis in SLE is rarely seen, and the follicular hyperplasia is usually considered as nonspecific. However, since the late 1990s, a few cases of SLE lymphadenopathy have been reported exhibiting a Castleman's disease (CD) morphology, which was discovered in lymph node biopsies. Here we report a similar case of SLE combined with CD in a 23-year-old girl who displayed systemic symptoms, including systemic lymphadenopathy and abnormal laboratory findings indicating the active phase of SLE. A biopsy of neck lymphnodes showed histopathological features of CD. The patient responded very well to the prednisolone treatment. Based on the related literature review, we would like to stress the possibility of CD in patients with SLE lymphadenopathy.
    Rheumatology International 03/2010; 32(7):2189-93. · 2.21 Impact Factor
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    ABSTRACT: Rhodococcus equi, previously known as Corynebacterium equi, is one of the most important causes of zoonotic infections in grazing animals. Increased cases of human infection with R. equi have been reported, especially in immunocompromised patients, within recent years. We present a case of R. equi bacteremia in a 51-year-old man with diabetes and liver cirrhosis, on long-term corticosteroid therapy after skin-grafting surgery. The patient recovered soon after he was treated with vancomycin. This review focuses on the microbiological characteristics of this organism, and the diagnosis and treatment of this infection.
    Journal of Zhejiang University SCIENCE B 12/2009; 10(12):933-6. · 1.11 Impact Factor
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    Chinese medical journal 07/2009; 122(12):1473-6. · 0.90 Impact Factor
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    ABSTRACT: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease. It was first described in China in 1965, and more cases have been reported subsequently. A systematic review was performed on 241 cases of PAP in China and progress in the diagnosis and treatment of this disease is discussed. The Chinese biological and medical databases from 1965 to 2006 were searched and 241 cases with complete clinical and pathological data were identified. The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time. The morbidity associated with PAP has increased in recent years. The clinical manifestations were non-specific. Progressive dyspnoea, cough and sputum were the most common symptoms. The percentage of patients undergoing CT examination has increased over the years. The combination of bronchoscopic biopsy and bronchoalveolar lavage (BAL) was usually sufficient to establish the diagnosis. Treatment was reported for a total of 142 cases. BAL and whole lung lavage were both effective and were only required once by most patients. The demographic characteristics and clinical manifestations of PAP patients in China are largely consistent with previous reports. Morbidity has increased dramatically in recent years, mainly due to the broad application of bronchoscopy since 1995. CT is very important for diagnosis of the disease. The long-term effects of treatment by whole lung lavage and BAL are similar.
    Respirology 06/2009; 14(5):761-6. · 2.78 Impact Factor
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    ABSTRACT: The conventional FEV(1)/FVC test is the "gold standard" to quantitate airway obstruction, but elderly subjects or patients with severe respiratory diseases quite frequently cannot make such an effort. Many studies have investigated the usefulness of FEV(1)/forced expired volume in 6 s (FEV(6)) measurements as an alternative for FEV(1)/FVC for diagnosis of airway obstruction. We conducted a meta-analysis to determine the FEV(1)/FEV(6) substitute for FEV(1)/FVC in the diagnosis of airway obstruction. After a systematic review of all-language studies, sensitivity, specificity, and other measures of accuracy of FEV(1)/FEV(6) in the diagnosis of airway obstruction were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Eleven studies met our inclusion criteria. The summary estimates for FEV(1)/FEV(6) in the diagnosis of airway obstruction in the studies included were as follows: sensitivity, 0.89 (95% confidence interval [CI], 0.83 to 0.93); specificity, 0.98 (95% CI, 0.95 to 0.99); positive likelihood ratio, 45.46 (95% CI, 18.26 to 113.21); negative likelihood ratio, 0.11 (95% CI, 0.08 to 0.17); diagnostic odds ratio, 396.02 (95% CI, 167.32 to 937.31); and diagnostic score, 5.98 (95% CI, 5.12 to 6.84). FEV(1)/FEV(6) is a sensitive and specific test for the diagnosis of airway obstruction. FEV(1)/FEV(6) can be used as a valid alternative for FEV(1)/FVC in the diagnosis of airway obstruction.
    Chest 05/2009; 135(4):991-8. · 5.85 Impact Factor
  • Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 12/2008; 31(11):801-2.
  • Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 12/2008; 31(11):841-3.
  • Zhonghua bing li xue za zhi Chinese journal of pathology 12/2008; 37(11):787-8.
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    ABSTRACT: Thymic stromal lymphopoietin (TSLP) emerges as a central mediator of T helper cell (Th)2-dominant allergic diseases. However, the role of TSLP receptor (TSLPR) in allergen-induced Th2 priming, and the effects of TSLP signaling blocking on the development of asthma remain unclear. Here we showed that allergen challenge caused a rapid accumulation of TSLP in the airways of asthmatic mice, correlating well with eosinophils counts and interleukin (IL)-5 productions. When TSLP signaling was blocked by intratracheal administration of anti-TSLPR antibody before sensitization, eosinophilic airway inflammation, goblet cell hyperplasia and Th2 cytokines productions were significantly reduced. The alleviating effects of TSLPR blocking were achieved by inhibition of maturation and migration of airway dendritic cells (DCs), as well as their abilities of initiating CD4+T cell responses. Thus, local application of anti-TSLPR prevented Th2-mediated airway inflammation, at least partly, by regulating DCs function, which might be exploited to develop novel treatments for asthma.
    Clinical Immunology 09/2008; 129(2):202-10. · 3.77 Impact Factor
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    ABSTRACT: Streptococcus pneumoniae is the leading pathogen of community-acquired pneumonia and is a main cause of infectious deaths. However, little is known about host-pathogen interaction in human lung tissue. We tested the hypothesis that human alveolar macrophages (AMs) and alveolar epithelial cells (AECs) are important for initiating the host response against S. pneumoniae, and we evaluated the role of Toll-like receptor (TLR) 2, TLR4, and p38 mitogen-activated protein kinase (MAPK) signaling in the inflammatory response after pneumococcal infection. We established a novel model of acute S. pneumoniae infection using vital human lung specimens. In situ hybridization analysis showed that S. pneumoniae DNA was detected in 80 to 90% of AMs and 15 to 30% of AECs after in vitro infection accompanied by increased expression of inflammatory cytokines. Enhanced phosphorylation of p38 MAPK and increased TLR2 and 4 mRNA expression were observed in infected lung tissue. Thirty to fifty percent of AMs and 10 to 20% of AECs showed evidence of apoptosis 24 hours after pneumococcal infection. After macrophage deactivation with Clodronate/liposomes, infected lung tissue exhibited a significantly decreased release of inflammatory mediators. Inhibition of p38 MAPK signaling markedly reduced inflammatory cytokine release from human lungs, whereas TLR2 blockade revealed only minor effects. AMs are central resident immune cells during S. pneumoniae infection and are the main source of early proinflammatory cytokine release. p38 MAPK holds a major role in pathogen-induced pulmonary cytokine release and is a potential molecular target to modulate overwhelming lung inflammation.
    American Journal of Respiratory Cell and Molecular Biology 06/2008; 39(5):522-9. · 4.15 Impact Factor
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    ABSTRACT: To investigate the role of mitogen activated protein kinase (MAPK) pathway in the inflammatory response induced by nontypeable Haemophilus influenzae (NTHi). NTHi was a clinical isolate identified by serum agglutination test and 16S rRNA gene sequencing. The peripheral monocytes isolated from adult healthy donors were divided into medium-treated group, NTHi-stimulated group, SB203580 (p38 MAPK inhibitor) -pretreated group and UO126 (p44/42 MAPK inhibitor) -pretreated group. Monocytes were co-cultured with NTHi and harvested 1 h and 4 h after stimulation. The phosphorylation of p38 and p44/42 MAPKs was detected by Western blot. The expression of toll-like receptor 4 (TLR4) was examined by flow cytometry 16 h after bacterial stimulation. Monocytes were preincubated with SB203580 or UO126 for 1 h and then stimulated with NTHi for 4 h and 16 h, respectively. The level of TNF-alpha in the supernatants was determined by Enzyme-linked immunosorbent assay (ELISA). The phosphorylation of p38 MAPK and p44/42 MAPK was rapidly induced by NTHi and continued for at least 4 h after stimulation. The expression of TLR4 on monocytes after NTHi stimulation was significantly up-regulated compared with the control group (11.8 +/- 1.6 vs 4.8 +/- 0.6, P < 0.05). The leve of TNF-alpha in the supernatants was increased 4 h and 16 h after bacterial stimulation compared with the control group (4 h : 16.4 +/- 5.3 vs 0.6 +/- 0.6, P < 0.01; 24 h : 30.2 +/- 10.7 vs 1.4 +/- 1.1, P < 0.01). SB203580 pretreatment decreased remarkably the TNF-alpha secretion from monocytes (P < 0.05) whereas UO126 had no significant effect on TNF-alpha level (P > 0.05). TLR4 is probably involved in the inflammatory response of monocytes induced by NTHi whereas p38 MAPK is the key signal molecule in this inflammatory reaction.
    Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 05/2008; 31(5):348-51.
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    ABSTRACT: Nontypeable Haemophilus influenzae (NTHi) is an important respiratory pathogen implicated as an infectious trigger in chronic obstructive pulmonary disease, but its molecular interaction with human lung epithelial cells remains unclear. Herein, we tested that the hypothesis that NTHi induces the expression of cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) via activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B in pulmonary alveolar epithelial cells. Human alveolar epithelial A549 cells were infected with different concentrations of NTHi. The phosphorylation of p38 MAPK was detected by Western blot analysis, the DNA binding activity of NF-kappa B was assessed by electrophoretic mobility shift assay (EMSA), and the expressions of COX-1 and 2 mRNA and PGE2 protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. The roles of Toll-like receptor (TLR) 2 and TLR4, well known NTHi recognizing receptor in lung epithelial cell and gram-negative bacteria receptor, respectively, on the NTHi-induced COX-2 expression were investigated in the HEK293 cells overexpressing TLR2 and TLR4 in vitro and in the mouse model of NTHi-induced pneumonia by using TLR2 and TLR4 knock-out mice in vivo. In addition, the role of p38 MAPK and NF-kappa B on the NTHi-induced COX-2 and PGE2 expression was investigated by using their specific chemical inhibitors. NTHi induced COX-2 mRNA expression in a dose-dependent manner, but not COX-1 mRNA expression in A549 cells. The enhanced expression of PGE2 by NTHi infection was significantly decreased by pre-treatment of COX-2 specific inhibitor, but not by COX-1 inhibitor. NTHi induced COX-2 expression was mediated by TLR2 in the epithelial cell in vitro and in the lungs of mice in vivo. NTHi induced phosphorylation of p38 MAPK and up-regulated DNA binding activity of NF-kappa B. Moreover, the expressions of COX-2 and PGE2 were significantly inhibited by specific inhibitors of p38 MAPK and NF-kappa B. However, NTHi-induced DNA binding activity of NF-kappa B was not affected by the inhibition of p38 MAPK. NTHi induces COX-2 and PGE2 expression in a p38 MAPK and NF-kappa B-dependent manner through TLR2 in lung epithelial cells in vitro and lung tissues in vivo. The full understanding of the role of endogenous anti-inflammatory PGE2 and its regulation will bring new insight to the resolution of inflammation in pulmonary bacterial infections.
    Respiratory research 02/2008; 9:16. · 3.64 Impact Factor