ABSTRACT
The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8+ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.
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Objective To observe the expression of epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF) in non-small cell lung cancer(NSCLC) and the reletionship with clinic-pathologic parameters.Methods Immunohistochemistry of tissue sections was used to study the expression of EGFR and VEGF in 124 NSCLC tissues and 15 normal lung tissues adjacent to cancer tissues.Results The positive rates of EGFR and VEGF in 124 NSCLC samples were 52.4％,66.1％,while no expressed in the 15 normal lung tissues adjacent to cancer tissues.The positive rate of VEGF with stage Ⅲ was higher than that with stage Ⅰ - Ⅱ ( 80.4％ vs 56.2％,P ＜0.05).The positive rate of VEGF with lymph node metastasis was higher than that without lymph node metastasis (78,2％ vs 53.3％,P ＜ 0.05 ).The expression of VEGF and EGFR had no relationship with clinic pathological factors including histological type of lung cancer,sex,age.EGFR and VEGF expression was statistically correlated with each other( r =0.93,P ＜0.05 ).Conclusion EGFR and VEGF were overexpressed in NSCLC tissues.The expression of VEGF was correlated with TNM stages and lymph node metastasis.The expression of EGFR was correlated with VEGF expression in NSCLC tissues,which indicates they might act synergistically in angiogenesis of NSCLC.
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It is purposed to analyze therapeutic effectiveness at community and designated hospitals for extensive influenza A H1N1 outbreaks at five universities in Qingdao,Shandong,east China during September 1 to 30,2009,including 28 confirmed cases,182 suspected cases and 136 close contacts treated at community health-care facilities,and 56 confirmed cases treated at designated hospitals.There was no significant difference in therapeutic effectiveness between community health-care facilities and designated hospitals (P ＞ 0.05).No new cases occurred seven days after their isolation was lifted for suspected cases and close contacts at community,indicating influenza A H1N1 could be prevented,controlled and cured and its mild cases could be treated at community health-care facilities.
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OBJECTIVE To explore production of ?-lactamase induced by antibiotics in Pseudomonas aeruginosa biofilm and planktonic bacteria.METHODS In vitro models of P.aeruginosa biofilm were built up.The planktonic bacteria and P.aeruginosa biofilms were exposed to different concentrations of imipenem and ceftazidime.The quantitative analysis of ?-lactamase was undertaken.The class of ?-lactamase was verified by modified cefoxitin three-dimensional test.RESULTS Both P.aeruginosa biofilm and planktonic bacteria showed significant ?-lactamase activity in the presence of antibiotics.The maximal ?-lactamase activities of both were significantly different with the statistic method of test(P
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Objective To study the anti-proliferative effects of Okam extract on bleomycin induced pulmonary fibrosis in rats and its underlying mechanisms.Methods Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin.Then test groups received daily Okam at doses of 25 and 50 mg?kg~(-1) orally and control group received normal saline.The expressions of collagen-Ⅲ.tumor necrosis factor(TNF-?) and vascular endothelial growth factor(VEGF) proteins were determined by immunohistochemistry.Results Pulmonary fibrosis of test groups was improved as compared with that of model group.Protein expressions of collagen-ll,VEGF and TNF-?in 50mg?kg~(-1)group were markedly lower than those in model group.Protein expressions of collagen-Ⅲand VEGF in 25 mg?kg~(-1)group were lower than those in model group,while protein expression of TNF-?showed no difference with that in model group.Conclusion Okam extract alleviates bleomycin induced pulmonary fibrosis in rats by inhibiting the expressions of collagen-Ⅲ,TNF-?and VEGF.
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OBJECTIVE To study the existence of the ?-lactamase gene produced by multidrug-resistant Pseudomonas aeruginosa isolated from respiratory tract. METHODS Antimicrobial susceptibility was tested by K-B method. A modified three-dimensional test was used to detect the ?-lactamase phenotypes. The genotypes were analyzed by PCR amplification and product sequencing. RESULTS ?-Lactamases were detected in 29 out of the 46 isolates. Twenty-one isolates produced AmpC ?-lactamase,two of them harboring CARB-3 gene. Two isolates produced ESBLs harbored TEM gene. Six isolates produced other type of ?-lactamases. Four out of 6 harbored CARB-3 gene and three IMP gene. The oprD2 gene was deleted in 34 isolates. CONCLUSIONS Chromosomal-mediated AmpC ?-lactamase is the major ?-lactamases produced by multidrug-resistant P. aeruginosa and CARB-3 is second. Lack oprD2 gene is popular.