[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play a crucial role in both innate and adaptive immune responses. DCs orient the immune responses by modulating the balance between protective immunity to pathogens and tolerance to self-antigens. Staphylococcus aureus (S. aureus) is a common member of human skin microbiota and can cause severe infections with significant morbidity and mortality. Protective immunity to pathogens by DCs is required for clearance of S. aureus. DCs sense the presence of the staphylococcal components using pattern recognition receptors (PRRs) and then orchestrate immune systems to resolve infections. This review summarizes the possible roles of DCs, in particularly their Toll-like receptors (TLRs) in S. aureus infection and strategies by which the pathogen affects activation and function of DCs.
Journal of Translational Medicine 12/2014; 12(1):358. · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vitamin D supplementation is believed to be beneficial in the treatment of patients with tuberculosis (TB), however, results from clinical trials have been inconclusive.
Chinese medical journal. 09/2014; 127(17):3127-34.
[Show abstract][Hide abstract] ABSTRACT: Chemokines are key mediators of leukocyte recruitment during immunoregulatory and proinflammatory responses. CCL20 is a cysteine-cysteine chemokine that was originally shown to be chemotactic for immature dendritic cells, effector or memory CD4(+) T lymphocytes, and B lymphocytes. Additionally CCL20 and its only receptor (CCR6) are exploited by cancer cells for migration and metastatic spread and play important roles in the development and progression of cancer. However, it still remains unclear how the activity of the CCL20/CCR6 axis is controlled and regulated at the transcriptional level. The CCL20 promoter region contains a transcription start site, a nuclear factor (NF)-κB binding site, CCAAT/enhancer-binding proteins binding site, activator protein-1 binding sites, specificity protein 1 (Sp1)-binding site. In this review, we outline recent advances in our understanding of the structure of the CCL20 promoter region and discuss the transcriptional regulation of the CCL20 promoter.
Microbes and Infection 08/2014; · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Revealing functional reorganization or module rewiring between modules at network levels during drug treatment is important to systematically understand therapies and drug responses. The present article proposed a novel model of module network rewiring to characterize functional reorganization of a complex biological system, and described a new framework named as module network rewiring-analysis (MNR) for systematically studying dynamical drug sensitivity and resistance during drug treatment. MNR was used to investigate functional reorganization or rewiring on the module network, rather than molecular network or individual molecules. Our experiments on expression data of patients with Hepatitis C virus infection receiving Interferon therapy demonstrated that consistent module genes derived by MNR could be directly used to reveal new genotypes relevant to drug sensitivity, unlike the other differential analyses of gene expressions. Our results showed that functional connections and reconnections among consistent modules bridged by biological paths were necessary for achieving effective responses of a drug. The hierarchical structures of the temporal module network can be considered as spatio-temporal biomarkers to monitor the efficacy, efficiency, toxicity, and resistance of the therapy. Our study indicates that MNR is a useful tool to identify module biomarkers and further predict dynamical drug sensitivity and resistance, characterize complex dynamic processes for therapy response, and provide biologically systematic clues for pharmacogenomic applications.
Drug Resistance Updates 07/2014; · 8.82 Impact Factor
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: Acute lung injury (ALI) is a severe clinical condition responsible for high mortality and the development of multiple organ dysfunctions, because of the lack of specific and effective therapies for ALI. Increasing evidence from pre-clinical studies supports preventive and therapeutic effects of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in ALI/ARDS (acute respiratory distress syndrome). Therapeutic effects of MSCs were noticed in various delivery approaches (systemic, local, or other locations), multiple origins (bone marrow or other tissues), or different schedules of administrations (before or after the challenges). MSCs could reduce the over-production of inflammatory mediators, leucocyte infiltration, tissue injury and pulmonary failure, and produce a number of benefit factors through interaction with other cells in the process of lung tissue repair. Thus, it is necessary to establish guidelines, standard operating procedures and evaluation criteria for translating MSC-based therapies into clinical application for patients with ALI.
Journal of Cellular and Molecular Medicine 07/2013; · 3.70 Impact Factor
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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 11/2012; 7(11):e48278. · 3.53 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. · 1.02 Impact Factor
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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. · 1.63 Impact Factor
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.