摘要：
ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. The purpose of this study was to investigate the effects of betulinic acid (BA), a pentacyclic triterpenoid, on ABCA1 expression and cholesterol efflux, and to further determine the underlying mechanism. BA promoted ABCA1 expression and cholesterol efflux, decreased cellular cholesterol and cholesterol ester content in LPS-treated macrophages. Furthermore, we found that BA promoted ABCA1 expression via down-regulation of miR-33s. The inhibition of LPS-induced NF-kappa B activation further decreased miR-33s expression and enhanced ABCA1 expression and cholesterol efflux when compared with BA only treatment. In addition, BA suppressed I kappa B phosphorylation, p65 phosphorylation and nuclear translocation, and the transcription of NF-kappa B-dependent related gene. Moreover, BA reduced atherosclerotic lesion size, miR-33s levels and NF-kappa B activation, and promoted ABCA1 expression in apoE(-/-) mice. Taken together, these results reveal a novel mechanism for the BA-mediated ABCA1 expression, which may provide new insights for developing strategies for modulating vascular inflammation and atherosclerosis.
摘要：
To discover novel lung adenocarcinoma (AdC) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-tagging combined with 2D-LC-MS/MS analysis was used to identify differentially expressed plasma membrane proteins in lung AdC and paired paraneoplastic normal lung tissues (PNLTs) adjacent to tumors. In this study, significant caveolin-1 downregulation and integrin β1 upregulation was observed in primary lung AdC vs. PNLT. As there has been no report on the association of integrin β1 with lung AdC, immunohistochemical staining was performed to detect the expression of integrin β1 in an independent set of archival tissue specimens including 42 cases of PLNT, 46 cases of without lymph node metastasis primary AdC (non-LNM AdC) and 62 cases of LNM AdC; the correlation of their expression levels with clinicopathological characteristics and clinical outcomes were evaluated. Based on the data, upregulation of integrin β1 was significantly correlated with advanced clinical stage and lymph node metastasis. Integrin β1 overexpression was significantly associated with advanced clinical stage (P<0.05), lymph node metastasis (P<0.05), increased relapse rate (P<0.05) and decreased overall survival (P<0.05) in AdCs. Cox regression analysis indicated that integrin β1 overexpression is an independent prognostic factor. The data suggest that integrin β1 is a potential biomarker for LNM and prognosis of AdC and integrin β1 upregulation may play an important role in the pathogenesis of AdC.
通讯机构：
[Liao, Li] C;Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha 410008, Hunan, Peoples R China.
摘要：
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. Therefore, the biomarkers for predicting NPC response to radiotherapy are very important for targeted therapy and individualized radiotherapy of NPC. Accumulating evidences have shown that Annexin A1 was correlated with NPC radioresistance. First, Annexin A1 is a potential tumor suppressor gene, and can regulate tumor cell proliferation and apoptosis, thus abnormal expression of Annexin A1 in NPC affects apoptosis of tumor cells induced by ionizing radiation and radiotherapeutic efficacy. Second, Annexin A1 is one of the proteins that are involved in p53-mediated radioresponse in NPC, and it might be related to NPC radioresistance. Third, the expression level of Annexin A1 is down-regulated in NPC, and is correlated with metastasis, recurrence and poor prognosis of NPC, thus Annexin A1 downregulation may increase NPC radioresistance, leading to poor prognosis. Last but not the least, Annexin A1 is closely related with tumor chemoresistance, whereas radioresistance is similar to chemoresistance in many aspects, thus Annexin A1 may also be involved in NPC radioresistance. Based on the above mentions, we hypothesize that Annexin A1 is closely correlated with NPC radioresistance and is an important new biomarker for predicting NPC response to radiotherapy.
摘要：
The aim of this study was to explore the molecular mechanisms of the diallyl disulfide (DADS)-mediated downregulation of LIM kinase-1 (LIMK1) and the consequent inhibition of the migration and invasion of human colorectal cancer cells. RNA interference technology was used to establish stable LIMK1-miRNA/SW480 cell lines. The effects of DADS and LIMK1 RNA interference on the migration and invasion of SW480 cells were observed by scratch wound healing assay and Transwell migration assay. The effects of DADS on signaling molecules of the Rac1-Rho kinase (ROCK)1/p21-activated kinase (PAK)1-LIM kinase (LIMK)1-actin depolymerizing factor (ADF)/cofilin pathway in SW480 cells were examined by RT-PCR and western blot analysis. The healing and migration rate of the SW480 cells was significantly reduced and the cell penetrating ability was significantly suppressed (P<0.05) following treatment with DADS (45 mg/l). The immunohistochemistry and western blot analysis results showed that DADS significantly downregulated LIMK1 protein expression and suppressed LIMK1 protein phosphorylation. Furthermore, the RT-PCR and western blot analysis results revealed that DADS suppressed Rac1, ROCK1, PAK1, LIMK1 and destrin mRNA and protein expression, as well as the protein phosphorylation of LIMK1 and cofilin 1. The data demonstrate that LIMK1 expression positively correlates with the SW480 cell migration and invasion ability. DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, suppressing SW480 cell migration and invasion.
摘要：
Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against A beta-induced injury in vitro and in vivo. Neu-P11 (piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptor agonist and a serotonin 5-HT1A/1D receptor agonist recently developed for the treatment of insomnia. In the present study we firstly investigated whether Neu-P11 and melatonin enhance memory performance in the novel object recognition (NOR) task in rats, and then assessed whether Neu-P11 and melatonin improve neuronal and cognitive impairment in a rat model of Alzheimer' disease (AD) induced by intrahippocampal A beta((1-42)) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24 h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal A beta((1-42)) injection resulted in hippocampal cellular loss, as well as decreased learning ability and memory in the Y maze and NOR tasks in rats. Neu-P11 but not melatonin attenuated cellular loss and cognitive impairment in the rat AD model. The current data suggest that Neu-P11 may serve as a novel agent for the treatment of AD. (C) 2013 Elsevier Inc. All rights reserved.
摘要：
Tert-butylhydroquinone (tBHQ), a synthetic phenolic antioxidant, is commonly used as a food preservative because of its potent antilipid peroxidation activity. Several lines of evidence have demonstrated that dietary supplementation with antioxidants has an antiatherogenic function through reducing cholesterol uptake or promoting reverse cholesterol transport. In this study, we investigated whether tBHQ affects expression of ATP-binding cassette transporter A1 (ABCA1) and the potential subsequent effect on cellular cholesterol homeostasis. Methods and Results: tBHQ increased ABCA1 protein levels and markedly enhanced cholesterol efflux from THP-1 macrophage-derived foam cells. Furthermore, tBHQ reduced calpain-mediated ABCA1 proteolysis via activation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Inhibition of HO-1 with a pharmacological inhibitor or siRNA and knockdown of Nrf2 suppressed the stimulatory effects of tBHQ on ABCA1 expression and calpain activity. Conclusions: Nrf2/HO-1 signaling is required for the regulation by tBHQ of ABCA1 expression and cholesterol efflux in macrophage-derived foam cells and an antiatherogenic role of tBHQ is suggested.
作者机构：
[Qu, Jia-Quan; Li, Cui; Yi, Hong; Li, Mao-Yu; Xiao, Zhi-Qiang; Zhang, Peng-Fei; Li, Xin-Hui; Zeng, Gu-Qing; Hu, Rong] Cent S Univ, Xiangya Hosp, Chinese Minist Hlth, Key Lab Canc Prote, Changsha, Hunan, Peoples R China.;[Zeng, Gu-Qing] Univ South China, Sch Nursing, Hengyang, Hunan, Peoples R China.;[Deng, Xingming] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA.;[Deng, Xingming] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
通讯机构：
[Deng, Xingming] E;Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA.
关键词：
Carcinogenesis;Lung and intrathoracic tumors;Selenium;Epithelial cells;Apoptosis;Prostate cancer;Protein expression;Proteomics
摘要：
BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1) was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC) carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.
通讯机构：
[Tang, Chao-Ke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Hunan, Peoples R China.
关键词：
ATP-binding cassette transporter A1;Interleukin-12;Interleukin-18;Liver X receptor alpha;Nuclear factor-kappa B
摘要：
Background: Interleukin (IL)-18 and IL-12 synergize for the production of interferon (IFN)-γ, which can downregulate ATP-binding cassette transporter A1 (ABCA1) expression. The aim of the present study was to investigate the effect of IL-18 and/or IL-12 on ABCA1 expression. Methods and Results: IL-18 combined with IL-12 decreased ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells, whereas IL-18 or IL-12 alone had no effect. IL-12 increased IL-18 receptor (IL-18R) expression, which was suppressed by small interfering RNA (siRNA) for signal transducer and activator of transcription 3. IL-18R but not IL-12 receptor siRNA completely reversed the effects of IL-18 and IL-12 on ABCA1 expression and cellular cholesterol efflux. Treatment with IL-18 plus IL-12 markedly augmented nuclear translocation of nuclear factor (NF)-κB but had no effect on expression and activity of liver X receptor α. IL-18 and IL-12 also significantly increased zinc finger protein 202 (ZNF202) levels and IFN-γ secretion. Furthermore, siRNA for ZNF202 or IFN-γ significantly impaired IL-18/IL-12-induced suppression of ABCA1, whereas NF-κB siRNA treatment blocked IL-18/IL-12' action on ZNF202 levels, IFN-γ secretion, and ABCA1 expression. Conclusions: IL-18 and IL-12 together can decrease ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells through the IL-18R/NF-κB signaling pathway.
作者机构：
[Yu, Xiaohua; Zhao, Guojun; Yin, Kai; Li, Xiaoxu; Tang, Chaoke; Jiang, Zhisheng; Xiao, Ji; Mo, Zhongcheng] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.;[Yu, Xiaohua] Univ S China, Sch Nursing, Hengyang 421001, Peoples R China.;[Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;[Zha, Xiaohui] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
通讯机构：
[Tang, Chaoke] U;Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Life Sci Res Ctr, Hengyang 421001, Peoples R China.
关键词：
Niemann–Pick type C1;oxLDL;ERK1/2;COX-2;PPARα;cholesterol
摘要：
The Niemann–Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane. It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression. However, the detailed mechanisms are not fully understood. In this study, we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages. Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner. In addition, oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2) mRNA and protein expression in the macrophages, and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment. OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels, which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages. OxLDL dramatically elevated cellular cholesterol efflux, which was abrogated by inhibiting ERK1/2 and/or COX-2. In addition, oxLDL-induced NPC1 expression and cellular cholesterol efflux were reversed by PPARα siRNA or GW6471, an antagonist of PPARα. Taken together, these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.
摘要：
Background Macrophage migration inhibitory factor (MIF) is an upstream regulator in immune and inflammatory responses. However, its role in viral myocarditis remains unknown. In this study, we investigated the role of the MIF in coxsackievirus B3 (CVB3)-induced myocarditis. Methods Mice were randomized into two groups receiving either Eagle’s minimal essential medium (EMEM, control group) or virus solution (infected group). Subsets of mice in the infected group were sacrificed on days 3, 7, 14 and 28 after inoculation. Expression of MIF was detected using an enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction and immunohistochemistry. A neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 7 after inoculation. Disease severity was estimated by histopathology of the heart and by the heart weight to body weight ratio, and the interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the myocardium were measured by ELISA on day 14. Results The serum MIF concentration and expression levels of myocardial MIF mRNA and protein were significantly elevated in mice on days 7 and 14 post-infection. The survival rate was markedly higher and disease severity was obviously less in mice treated with anti-MIF Ab. Furthermore, MIF blockade significantly decreased the IL-1β and TNF-α in the myocarditic heart. Conclusion These results demonstrate that MIF is an important naturally occurring inflammatory cytokine in CVB3-induced myocarditis, and anti-MIF Ab may lessen the inflammatory response.
期刊：
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH,2011年65(8):722-726 ISSN：0143-005X
通讯作者：
Wen, S. W.
作者机构：
[Wen, S. W.; Guo, Y.; Walker, M.; Xie, R-H] Univ Ottawa, OMNI Res Grp, Dept Obstet & Gynecol, Fac Med, Ottawa, ON K1H 8L6, Canada.;[Wen, S. W.; Guo, Y.; Walker, M.; Xie, R-H] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada.;[Xie, R-H] Huaihua Med Coll, Dept Nursing, Huaihua, Peoples R China.;[Wen, S. W.; Liao, S.; Guo, Y.] Cent S Univ, Sch Publ Hlth, Changsha, Hunan, Peoples R China.;[Xie, H.] Univ S China, Sch Nursing, Hengyang, Hunan, Peoples R China.
通讯机构：
[Wen, S. W.] U;Univ Ottawa, OMNI Res Grp, Dept Obstet & Gynecol, Fac Med, 501 Smyth Rd,Box 241, Ottawa, ON K1H 8L6, Canada.
摘要：
Objectives To assess the impact of prenatal and postnatal family support on the association between infant sex and postpartum depression (PPD). Design Prospective cohort study. Setting Pregnant women seen at Hunan Maternal and Infant Hospital, the First Affiliated and the Third Affiliated Hospitals of the Central South University in Changsha, Hunan, People's Republic of China from February to September 2007. Participants 534 Pregnant women who were consecutively recruited from the participating hospital during their prenatal visits at 30-32 weeks of gestation and who completed the 2 weeks postpartum survey, with no recorded major psychiatric disorders and obstetric and/or pregnancy complications. Main outcome measure PPD, which was defined as a score of 13 or higher of the Edinburgh Postnatal Depression Scale. Results Postnatal family support scores were much lower in women who gave birth to a female infant, and the OR of PPD was 3.67 (95% CI 2.31 to 5.84) for them as compared to women who gave birth to a male infant. After adjusting by postnatal support from all family members, husband and parents, the ORs of PPD for women who gave birth to a female infant decreased to 2.06 (95% CI 1.20 to 3.53), 2.89 (95% CI 1.76 to 4.77) and 2.20 (95% CI 1.28 to 3.77), respectively. Discussion Increased risk of PPD in Chinese women who gave birth to a female infant can be explained to large extent by inadequate or poor postpartum support from family members, particularly husband and parents.
