%0 Journal Article %~ PubMed %A Najib, Elias %A Puranik, Rajesh %A Duflou, Johan %A Xia, Qiong %A Bao, Shisan %T Age related inflammatory characteristics of coronary artery disease. %B International journal of cardiology %D 2012 %C Ireland %I Elsevier Ireland Ltd %V 154 %N 1 %P 65-70 %@ 0167-5273 %X Coronary heart disease, often associated with fatal outcomes, is increasingly common. Immune dysregulation is a key process in atherogenesis, yet age and other immune related factors are poorly characterised, especially in premature disease. The current study is to investigate the differential immunological mediators in the plaque specific to older and younger decedents. %Z FOR Codes: 110201 %0 Journal Article %~ PubMed %A Xia, Qiong %A Xiang, Xiaogang %A Patel, Sanjay %A Puranik, Rajesh %A Xie, Qing %A Bao, Shisan %T Characterisation of IL-22 and interferon-gamma-inducible chemokines in human carotid plaque. %B International Journal of Cardiology %D 2012 %C Ireland %I Elsevier Ireland Ltd %V 154 %N 2 %P 187-189 %@ 0167-5273 %X %Z FOR Codes: 110201 %0 Journal Article %~ PubMed %A Wu, Buchu %A Hu, Ke %A Li, Shu %A Zhu, Jing %A Gu, Liying %A Shen, Haoran %A Hambly, Brett D %A Bao, Shisan %A Di, Wen %T Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer. %B Oncology Reports %D 2012 %C Greece %I Spandidos Publications %V 27 %N 1 %P 101-108 %@ 1791-2431 %X Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Xiang, Xiaogang %A Gui, Honglian %A King, Nicholas Jc %A Cole, Louise %A Wang, Hui %A Xie, Qing %A Bao, Shisan %T IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected liver. %B Immunology and Cell Biology %D 2012 %C United Kingdom, Australia %I Nature Publishing Group %V 90 %N 6 %P 611-619 %@ 0818-9641 %X Hepatitis B virus infection is still a major global health problem, despite decades of research. Interleukin (IL)-22 induces acute phase reactants and chemokines, favors anti-microbial defence and protects tissues from damage. IL-22 is important in chronic skin inflammation, but its role in chronic hepatitis B (CHB) is unclear. This study explores the association between intra-hepatic IL-22 expression, its relevant associated cytokines and the severity of liver inflammation/fibrosis in CHB patients. IL-22, IL-17, IL-10, IL-6, non-ELR-CXC chemokines (CXCL-9, CXCL-10, CXCL-11), fibroblast growth factors and Kupffer cell (KC) numbers were measured in patients with CHB (n=65), acute hepatitis B (AHB; n=4), chronic hepatitis C (CHC; n=14) and non-viral hepatitis (n=23), using immunohistochemistry. Expression of IL-22, IL-17, IL-10, IL-6, non-ELR-CXC chemokines and number of KCs in liver tissues were substantially higher in AHB patients than others. In CHB patients, the expression of IL-22, IL-6, CXCL-9 and CXCL-10 were significantly higher with alanine aminotransferase (ALT) levels ???twice the upper limit of normal (ULN), compared with those with ALT levels >twice the ULN, whereas IL-10 and IL-17 showed a reverse pattern. IL-22 was inversely (P<0.01), but IL-17 was positively (P<0.05), correlated with the histological activity index) in these patients, and a significant negative correlation between the fibrosis stage and IL-22 or non-ELR-CXC chemokines was observed. Furthermore, immunofluorescent labeling demonstrated a close spatial association of IL-22, CXCL-9, -10 or -11 in the CHB liver. We speculate that IL-22 and non-ELR-CXC chemokines synergistically may provide protection in liver inflammation/fibrosis during CHB infection.Immunology and Cell Biology advance online publication, 27 September 2011; doi:10.1038/icb.2011.79. %Z FOR Codes: 110704 110804 1107 %0 Journal Article %~ PubMed %A Zhao, Gangde %A An, Baoyan %A Zhou, Huijuan %A Wang, Hui %A Xu, Yumin %A Xiang, Xiaogang %A Dong, Zhixia %A An, Fangmei %A Yu, Dongshan %A Wang, Weijing %A Bao, Shisan %A Xie, Qing %T Impairment of the retinoic acid-inducible gene-I-IFN-β signaling pathway in chronic hepatitis B virus infection %B International Journal of Molecular Medicine %D 2012 %C Greece %I Spandidos Publications %V 30 %N 6 %P 1498-1504 %@ 1791-244X %X %Z FOR Codes: 30405 %0 Journal Article %~ PubMed %A Waterhouse, Anna %A Wise, Steven G %A Yin, Yongbai %A Wu, Buchu %A James, Barbara %A Zreiqat, Hala %A McKenzie, David R %A Bao, Shisan %A Weiss, Anthony S %A Ng, Martin K C %A Bilek, Marcela M M %T In vivo biocompatibility of a plasma-activated, coronary stent coating. %B Biomaterials %D 2012 %C Netherlands %I Elsevier BV %V 33 %N 32 %P 7984-7992 %@ 0142-9612 %X Bare metal and drug-eluting coronary stents suffer an inherent lack of vascular cell and blood compatibility resulting in adverse patient responses. We have developed a plasma-activated coating (PAC) for metallic coronary stents that is durable, withstands crimping and expansion, has low thrombogenicity and can covalently bind proteins, linker-free. This has been shown to enhance endothelial cell interactions in??vitro and has the potential to promote biointegration of stents. Using the rabbit denuded iliac artery model, we show for the first time that PAC is a feasible coating for coronary stents in??vivo. The coating integrity of PAC was maintained following implantation and expansion. The rate of endothelialization, strut coverage, neointimal response and the initial immune response were equivalent to bare metal stents. Furthermore, the initial thrombogenicity caused by the PAC stents showed a reduced trend compared to bare metal stents. This work demonstrates a robust, durable, non-cytotoxic plasma-based coating technology that has the ability to covalently immobilize bioactive molecules for surface modification of coronary stents. Improvements in the clinical performance of implantable cardiovascular devices could be achieved by the immobilization of proteins or peptides that trigger desirable cellular responses. %Z FOR Codes: 90304 %0 Journal Article %~ PubMed %A Tavakoli, Nasim Nik %A Harris, Angie K %A Sullivan, David R %A Hambly, Brett D %A Bao, Shisan %T Interferon-γ deficiency reduces neointimal formation in a model of endoluminal endothelial injury combined with atherogenic diet. %B International Journal of Molecular Medicine %D 2012 %C Greece %I Spandidos Publications %V 30 %N 3 %P 545-552 %@ 1791-244X %X Interferon (IFN)-?? has been implicated in restenosis, however its precise role in the pathophysiology of neointimal formation following angioplasty is unclear, as it has been shown to both promote and inhibit neointimal formation. Dietary-induced hypercholesterolemia enhances injury-mediated neointimal formation, associated with increased systemic inflammation and serum IFN-??. This study examined the effect of IFN-?? gene deficiency (-/-) on neointimal formation in a mouse model of endothelial injury combined with an atherogenic diet. Neointimal formation was induced via endoluminal endothelial injury of the common iliac arteries of IFN-??-/- and wild-type (WT) C57Bl/6 mice. Histopathological analysis of the arteries was performed at 3 and 6 weeks post-surgery. IFN-??-/- mice demonstrated a significant reduction in neointimal formation at the 3???week time point, compared to their WT counterpart. No significant differences in plasma lipid profile and the extent of re-endothelialization were detected between IFN-??-/- and WT mice, suggesting that the effect of IFN-?? on neointimal formation is due to injury-mediated vessel neointimal responses. In support of the histopathological findings, immunohistochemical analysis revealed a significant reduction in vessel infiltrating macrophages, and neointimal PDGF-B expression, vascular smooth muscle cell composition and cellular proliferation in the IFN-??-/- mice, in comparison to their corresponding WT group at the 3-week time point. In conclusion, the IFN????????mediated pathway plays an important role in inflammatory responses and proliferative effects following injury, suggesting that modulation of the IFN-?? pathway would be beneficial in controlling neointimal formation and restenosis. %Z FOR Codes: 110201 %0 Journal Article %~ PubMed %A Wu, Buchu %A Li, Shu %A Sheng, Lili %A Zhu, Jing %A Gu, Liying %A Shen, Haoran %A La, Duanduan %A Hambly, Brett D %A Bao, Shisan %A Di, Wen %T Metformin inhibits the development and metastasis of ovarian cancer. %B Oncology Reports %D 2012 %C Greece %I Spandidos Publications %V 28 %N 3 %P 903-908 %@ 1791-2431 %X The aim of this study was to investigate the role of metformin in the regulation of development and metastasis of ovarian carcinoma cell lines in vitro and ovarian cancer in a nude mouse model in vivo. The effects of metformin on the ability of two high-metastatic potential human ovarian cancer cell lines (SKOV3 and HO8910-PM) to adhere, invade and migrate in vitro were observed by means of a cell adhesion test, cell invasion test and cell migration test. The size and number of the inoculated and metastatic tumours in vivo in a nude mouse were determined following intraperitoneal injection of metformin. Furthermore, the extent of angiogenesis (vWF) and macrophage infiltration in the tumour were determined. Proliferation, migration, invasion and adhesion of ovarian cancer cells were significantly inhibited (P<0.05) in a dose-dependent manner in vitro. In addition, metformin inhibited hepatic, intestinal and lung metastasis (P<0.05), with no weight loss in vivo, consistent with decreased expression of vWF and macrophage infiltration. Our data suggest that metformin inhibits the development and metastasis of ovarian cancer by reducing cellular-ECM interactions, neovascularisation and macrophage infiltration. %Z FOR Codes: 111201 %0 Book Section %A Chami, Belal %A Bao, Bob %T Salmonella: Invasion, Evasion & Persistence %B Salmonella - Distribution, Adaptation, Control Measures and Molecular Technologies %D 2012 %C Croatia %I InTech %V %N %P 313-338 %@ 9789535106616 %X %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A An, Fangmei %A Gong, Bangdong %A Wang, Hui %A Yu, Dongshan %A Zhao, Gangde %A Lin, Lanyi %A Tang, Weiliang %A Yu, Hong %A Bao, Shisan %A Xie, Qing %T miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure. %B Apoptosis %D 2012 %C United States %I Springer New York LLC %V 17 %N 7 %P 702-716 %@ 1573-675X %X Acute liver failure (ALF) still has an unacceptable high mortality rate, despite substantial improvements with multidisciplinary care. The precise underlying mechanism of ALF remains to be explored. It has been reported that microRNAs (miRNAs) are novel regulators in a number of liver diseases, but the role of miRNAs in the development of ALF is not fully understood. An ALF murine model was generated by ip injection of D: -GalN/LPS, which was confirmed with histopathology and biochemistry. The hepatic miRNA expression profile in ALF was determined by microarray and verified by qRT-PCR. The functions and signal pathways of the targeted genes of these deregulated miRNAs were predicted, using bioinformatics analysis. The possible underlying mechanism was investigated by exploring the relationship between miRNA modification and hepatocyte apoptosis. There were a total of 95 significantly changed miRNAs in ALF compared to mock-treated (P < 0.01). Among these 95 miRNAs, 20 were up-regulated and 26 were down-regulated at both 5 and 7 h time points. Bioinformatics analysis predicted that some of these 46 miRNAs were involved in apoptosis. Among the up-regulated miRNAs involved in apoptosis, miR-15b and miR-16 showed the highest enrichment and targeted the common anti-apoptotic gene, BCL2. Our in vitro data demonstrated that miR-15b and/or miR-16 regulated BCL2 at the protein level. Inhibition of miR-15b and/or miR-16 reduced hepatic apoptosis and TNF production. These data suggest that miR-15b and miR-16 regulate TNF mediated hepatic apoptosis via BCL2 during ALF, and may shed light on the development of a therapeutic strategy for treatment of ALF. %Z FOR Codes: 60103 %0 Journal Article %~ PubMed %A Bao, Shisan %A Carr, Emma Dj %A Xu, Ying-Hua %A Hunt, Nicholas H %T Gp91(phox) contributes to the development of experimental inflammatory bowel disease. %B Immunology and cell biology %D 2011 %C United Kingdom, Australia %I Nature Publishing Group %V 89 %N 8 %P 853-60 %@ 0818-9641 %X Inflammatory bowel disease (IBD) is related to dysfunction of intestinal immunity. Neutrophils have an important role in innate immunity via the oxidative burst, using the p47phox- and gp91(phox)-containing NAD(P)H oxidase known as Nox2. In dextran sulphate sodium (DSS)-induced colitis, no significant difference in inflammation between p47(phox-/-) and wild-type (WT) mice was reported, but there was improved endothelium-dependent arteriolar dilation in gp91(phox-/-) mice, compared with that in WT mice. Gp91(phox) and p47 (phox) are not only essential components of phagocyte Nox2, but also have roles in other enzymes. Thus the differences in response of their respective gene knockout mice to DSS challenge are not completely unexpected, but need further investigation. The clinicopathological changes and immunological responses to DSS challenge have not been fully described in gp91(phox-/-) mice. Thus we treated WT and gp91(phox-/-) mice with 2.5% DSS for 7 days. The gp91(phox-/-) mice developed less severe colitis than WT mice following DSS treatment, reflected by a smaller body weight loss, less rectal bleeding and fewer histopathological changes. Less colonic myeloperoxidase was observed in gp91(phox-/-), compared with WT mice, following DSS challenge, correlating with interleukin (IL)-6 production. IL-10 was upregulated in both gp91(phox-/-) and WT mice, but was significantly higher in the latter, following 7 days DSS challenge. These results suggest that gp91(phox-/-) mice are less susceptible to acute DSS-induced colitis, possibly because of a reduced oxidative burst in the intestine and, consequently, less tissue damage. %Z FOR Codes: 60105 110704 %0 Journal Article %~ PubMed %A Di Bartolo, B A %A Chan, J %A Bennett, M R %A Cartland, S %A Bao, S %A Tuch, B E %A Kavurma, M M %T TNF-related apoptosis-inducing ligand (TRAIL) protects against diabetes and atherosclerosis in Apoe ( -/- ) mice. %B Diabetologia %D 2011 %C Germany %I Springer %V 54 %N 12 %P 3157-3167 %@ 0012-186X %X AIMS/HYPOTHESIS: TNF-related apoptosis-inducing ligand (TRAIL) is implicated in the regulation of diabetes and is reduced in patients with cardiovascular disease. Although TRAIL receptors are widespread, and TRAIL can promote cell proliferation and apoptosis, it is not known how TRAIL might protect against diabetes and atherosclerosis. METHODS: We examined the development of atherosclerosis and diabetes in Apoe (-/-), Trail (also known as Tnfsf10)( -/- ) Apoe ( -/- ) and Trail ( -/- ) mice that were fed a high-fat diet. Plasma cholesterol, triacylglycerol, glucose and insulin, as well as changes in various metabolic enzymes and regulators were assessed. Glucose and insulin tolerance tests were performed. Pancreatic islets were examined for insulin and beta cell dysfunction (apoptosis and macrophage infiltration). RESULTS: Compared with Apoe ( -/- ) mice, Trail ( -/- ) Apoe ( -/- ) and Trail ( -/- ) mice exhibited several features of diabetes, including increased weight, hyperglycaemia, reduced plasma insulin, impaired glucose tolerance, beta cell dysfunction, reduced islet insulin, macrophage infiltration and increased apoptosis. Trail ( -/- ) Apoe ( -/- ) mice had increased plasma cholesterol, triacylglycerol, and VLDL- and LDL-cholesterol, and increased expression of genes involved in cholesterol synthesis and lipogenesis. Trail ( -/- ) Apoe ( -/- ) mice also had increased atherosclerosis, with several features of plaque instability. CONCLUSIONS/INTERPRETATION: We show for the first time that TRAIL deficiency promotes numerous features of diabetes that are typical of human disease, and are associated with reduced insulin and pancreatic inflammation/apoptosis. TRAIL also regulates cholesterol and triacylglycerol homeostasis in Apoe ( -/- ) mice by increasing the expression of genes involved in (1) cholesterol synthesis and absorption, and (2) triacylglycerol production. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Di Bartolo, Belinda A %A Nicholls, Stephen J %A Bao, Shisan %A Rye, Kerry-Anne %A Heather, Alison K %A Barter, Philip J %A Bursill, Christina %T The apolipoprotein A-I mimetic peptide ETC-642 exhibits anti-inflammatory properties that are comparable to high density lipoproteins. %B Atherosclerosis %D 2011 %C Ireland %I Elsevier Ireland Ltd. %V 217 %N 2 %P 395-400 %@ 0021-9150 %X Mimetic peptides of apolipoprotein A-I (apoA-I) present a new strategy for promoting the biological activity of high density lipoproteins (HDL). This study aimed to compare the anti-inflammatory effects of ETC-642, a new apoA-I mimetic peptide, with discoidal reconstituted HDL (rHDL). %Z FOR Codes: 110104 %0 Journal Article %~ PubMed %A Di Bartolo, Belinda A %A Vanags, Laura Z %A Tan, Joanne Tm %A Bao, Shisan %A Rye, Kerry-Anne %A Barter, Philip J %A Bursill, Christina A %T The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit. %B Lipids in Health and Disease %D 2011 %C United Kingdom %I BioMed Central Ltd. %V 10 %N %P 224 %@ 1476-511X %X ABSTRACT: %Z FOR Codes: 110201 %0 Journal Article %~ PubMed %A Xiang, Xiaogang %A Lu, Jie %A Dong, Zhixia %A Zhou, Huijuan %A Tao, Wanyin %A Guo, Qing %A Zhou, Xiaqiu %A Bao, Shisan %A Xie, Qing %A Zhong, Jin %T Viral sequence evolution in Chinese genotype 1b chronic hepatitis C patients experiencing unsuccessful interferon treatment. %B Infection, Genetics and Evolution %D 2011 %C Netherlands %I Elsevier BV %V 11 %N 2 %P 382-390 %@ 1567-7257 %X The efficiencies of IFN-? based therapy in chronic genotype 1b HCV patients are still unsatisfied to date. The mechanisms underlining treatment failure remain unclear and controversial. To investigate HCV sequence evolution in unsuccessfully treated genotype 1b patients before, during and after the therapy, full-length open-reading-frame of HCV genomes at week 0, week 48 and year 5 in one breakthrough and one nonresponse patients were amplified by reverse transcription (RT)-nested-PCR and sequenced. Mutations were scored and analyzed according to their locations in the HCV genome. HCV sequences in the breakthrough patient displayed significantly more mutations during the one-year therapy than that in the nonresponse patient, with p7 and NS2 encoding regions having the highest mutation rates. Most of the mutations selected during the therapy phase in the breakthrough patient were maintained and few new mutations arose in the four-year post-therapy phase, suggesting these mutations might not compromise viral fitness. Altogether our data suggest that mutations occurred during the therapy phase in the breakthrough patient are likely driven by the action of interferon and ribavirin, and these mutations may have important effects on the responses to interferon based therapy in genotype 1b HCV patients. %Z FOR Codes: 60411 110312 111706 %0 Journal Article %~ PubMed %A Sieveking, Daniel P %A Lim, Patrick %A Chow, Renée W Y %A Dunn, Louise L %A Bao, Shisan %A McGrath, Kristine C Y %A Heather, Alison K %A Handelsman, David J %A Celermajer, David S %A Ng, Martin K C %T A sex-specific role for androgens in angiogenesis. %B The Journal of Experimental Medicine %D 2010 %C United States %I Rockefeller University Press %V 207 %N 2 %P 345-352 %@ 1540-9538 %X Mounting evidence suggests that in men, serum levels of testosterone are negatively correlated to cardiovascular and all-cause mortality. We studied the role of androgens in angiogenesis, a process critical in cardiovascular repair/regeneration, in males and females. Androgen exposure augmented key angiogenic events in vitro. Strikingly, this occurred in male but not female endothelial cells (ECs). Androgen receptor (AR) antagonism or gene knockdown abrogated these effects in male ECs. Overexpression of AR in female ECs conferred androgen sensitivity with respect to angiogenesis. In vivo, castration dramatically reduced neovascularization of Matrigel plugs. Androgen treatment fully reversed this effect in male mice but had no effect in female mice. Furthermore, orchidectomy impaired blood-flow recovery from hindlimb ischemia, a finding rescued by androgen treatment. Our findings suggest that endogenous androgens modulate angiogenesis in a sex-dependent manner, with implications for the role of androgen replacement in men. %Z FOR Codes: 104 %0 Journal Article %~ PubMed %A Gong, Bang-Dong %A Xie, Qing %A Xiang, Xiao-Gang %A Wang, Lin %A Zhao, Gang-De %A An, Fang-Mei %A Wang, Hui %A Lin, Lan-Yi %A Yu, Hong %A Bao, Shi-San %T Effect of ribavirin and interferon beta on miRNA profile in the hepatitis C virus subgenomic replicon-bearing Huh7 cells. %B International Journal of Molecular Medicine %D 2010 %C Greece %I Spandidos Publications %V 25 %N 6 %P 853-859 %@ 1791-244X %X Hepatitis C virus (HCV) infection is still a major global health issue despite decades of research. The liver-specific microRNA-122 (miR-122) can stimulate HCV replication/translation in vitro, indicating that miR-122 contributes to pathogenesis of HCV. However, it remains controversial whether interferon (IFN) inhibits HCV via modulating miR-122 expression. The underlying mechanism of ribavirin (RBV) in enhancing IFN treatment for HCV patients has yet to be explored. We investigated the relationship between miR-122 expression and anti-HCV activity of IFN beta in combination with RBV in vitro, due to difficulty accessing an HCV animal model. Upregulation of ISG54 mRNA or cytostatic effect was detected in Huh7 and HCV replicon cell lines in response to IFN beta or RBV stimulation, respectively. It was found that IFN beta and/or RBV suppressed miR-122 expression marginally, with a synergetic anti-HCV effect between IFN beta and RBV. Marginal modification of other miRNAs was also observed in these cell lines, using miRNA array following IFN beta and RBV treatment. Taken together, our data suggest that miRNAs are not crucial in anti-HCV action, following IFN beta and/or RBV stimulation in vitro. %Z FOR Codes: 1108 %0 Journal Article %~ PubMed %A Fang, Y %A Shen, J %A Yao, M %A Beagley, K W %A Hambly, B D %A Bao, S %T Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines. %B The British journal of dermatology %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 162 %N 3 %P 478-86 %@ 1365-2133 %X Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives Using a diabetic mouse model, to investigate the role of GM-CSF in wound healing. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Puranik, R %A Fox, O J %A Sullivan, D S %A Duflou, J %A Bao, S %T Inflammatory characteristics of premature coronary artery disease. %B International journal of cardiology %D 2010 %C Ireland %I Elsevier Ireland Ltd %V 145 %N 2 %P 288-90 %@ 0167-5273 %X Although inflammation is a key process in atherogenesis, little is known about the inflammatory characteristics of culprit plaque in premature coronary artery disease (CAD). We investigated inflammation in coronary atheroma from subjects who died of premature CAD. From 2001-2005, we collected coronary plaque samples from consecutive cases of CAD (n=23) reported to the Department of Forensic Medicine which led to unexpected death in men aged <45 years. Coronary plaque from younger CAD decedents (<35 years, n=12) had lower levels of T cells (CD3+) (p=0.03), higher macrophage (CD 68+) (p=0.01) and T regulator cells (FOXP3+) (p=0.03) infiltration when compared to older CAD decedents (>35 years, n=11). Interestingly, there was no significant age-related difference between groups in the smooth muscle cell, apoA-I, myeloperoxidase and MMP-2 content within plaque. Hence, we demonstrate that higher expression of FOXP3 is associated with younger age at the time of fatal outcomes from CAD. These findings may have implications for plaque pathophysiology and thus warrant further investigation. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Nobécourt, Estelle %A Tabet, Fatiha %A Lambert, Gilles %A Puranik, Rajesh %A Bao, Shisan %A Yan, Ling %A Davies, Michael J %A Brown, Bronwyn E %A Jenkins, Alicia J %A Dusting, Gregory J %A Bonnet, David J %A Curtiss, Linda K %A Barter, Philip J %A Rye, Kerry-Anne %T Nonenzymatic glycation impairs the antiinflammatory properties of apolipoprotein A-I. %B Arteriosclerosis, Thrombosis, and Vascular Biology %D 2010 %C United States %I Lippincott Williams & Wilkins %V 30 %N 4 %P 766-772 %@ 1524-4636 %X OBJECTIVE: The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I. METHODS AND RESULTS: Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I(N)), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I(Glyc in vitro)), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I(Glyc in vivo)), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I(N), (A-I(N))rHDL, or apoA-I(Glyc in vitro), (A-I(Glyc in vitro))rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I(N) infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I(Glyc in vitro) infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I(Glyc in vivo) did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I(Glyc in vitro))rHDL also inhibited vascular inflammation less effectively than (A-I(N))rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-kappaB activation and reactive oxygen species formation. CONCLUSIONS: Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I. %Z FOR Codes: 30406 %0 Journal Article %~ PubMed %A Cai, Wei %A Xie, Qing %A An, Baoyan %A Wang, Hui %A Zhou, Xiaqiu %A Zhao, Guomin %A Guo, Qing %A Gu, Ruiying %A Bao, Shisan %T On-treatment serum HBsAg level is predictive of sustained off-treatment virologic response to telbivudine in HBeAg-positive chronic hepatitis B patients. %B Journal of Clinical Virology %D 2010 %C Netherlands %I Elsevier BV %V 48 %N 1 %P 22-26 %@ 1873-5967 %X BACKGROUND: Effective management of chronic hepatitis B infection is still very challenging, despite decades of clinical research. Telbivudine is one of the most frequently used antiviral drug at the current stage, but its long-term effectiveness, particularly at off-treatment, is still unclear. OBJECTIVES: To assess on-treatment HBsAg kinetics in patients treated with telbivudine for 2 years, and predicting sustained virologic response (SR) at 2 years off-treatment. STUDY DESIGN: Serum HBV DNA/HBsAg levels were assessed from 17 HBeAg+ patients treated with telbivudine 600 mg/day for 104 weeks, at baseline, weeks 24, 52 and 104, as well as during off-treatment follow-up. RESULTS: HBsAg levels <2 log(10)IU/ml at treatment week 104 were highly predictive of SR (i.e., HBV DNA <300 copies/ml, HBeAg seroconversion, ALT normalization) at 2 years off-treatment (positive predictive value [PPV], 93%; negative predictive value [NPV], 100%). HBsAg levels consistently declined from baseline only in patients achieving SR during 2 years off-treatment. At weeks 24 and 52, HBsAg decline rate was a better predictor of off-treatment response than HBV DNA decline rate. HBsAg decline rates of >0.8 and >1 log(10)IU/ml at treatment weeks 24 and 52 were predictive of SR (PPV, 75%; NPV, 86% at week 24; PPV, 75%; NPV, 86% at week 52). CONCLUSIONS: Serum HBsAg levels <2 log(10)IU/ml at treatment week 104 are highly predictive of SR to telbivudine at 2 years off-treatment. HBsAg decline rate at on-treatment weeks 24 and 52 from baseline were also more predictive of SR than HBV DNA decline rate. %Z FOR Codes: 1108 %0 Journal Article %~ PubMed %A Lin, L Y %A Wong, V W S %A Zhou, H J %A Chan, H Y %A Gui, H L %A Guo, S M %A Wang, H %A Huang, L %A Bao, S S %A Xie, Q %A Chan, H L Y %T Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients. %B Journal of Medical Virology %D 2010 %C United States %I John Wiley & Sons, Inc. %V 82 %N 9 %P 1494-1500 %@ 0146-6615 %X Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B. %Z FOR Codes: 1108 %0 Journal Article %A Gui, H L %A Wang, H %A Yang, Y H %A Wu, Y W %A Zhou, H J %A Guo, S M %A Lin, L Y %A Wang, L %A Cai, W %A Chen, R %A Guo, Q %A Zhou, X Q %A Bao, Shi San %A Xie, Q %T Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal ALT %B Journal of Viral Hepatitis %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 17 %N Suppl1 %P 44-50 %@ 1365-2893 %X %Z FOR Codes: 110307 %0 Journal Article %~ PubMed %A Patel, S %A Chung, S H %A White, G %A Bao, S %A Celermajer, D S %T The "atheroprotective" mediators apolipoproteinA-I and Foxp3 are over-abundant in unstable carotid plaques. %B International journal of cardiology %D 2010 %C Ireland %I Elsevier Ireland Ltd %V 145 %N 2 %P 183-7 %@ 0167-5273 %X Inflammation is important in plaque vulnerability but the role of atheroprotective mediators in unstable plaques is not defined. The apolipoproteinA-I (apoA-I) component of HDL, and CD4+/CD25+ regulatory T cells (with their major transcription factor, Foxp3), have been implicated in the suppression of vascular inflammation. Our aim was to characterise the presence of these novel "protective" markers (apoA-I and Foxp3) in carotid plaques from symptomatic and asymptomatic subjects. %Z FOR Codes: 110399 %0 Journal Article %~ PubMed %A Bebawy, Mary %A Rasmussen, Christine %A Sambasivam, Shwetha %A Bao, Shisan %T Dietary nucleotide supplements in infant formula modify the expression of P-glycoprotein in the intestinal epithelium in vitro. %B International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition %D 2009 %C Switzerland %I Verlag Hans Huber AG %V 79 %N 5-6 %P 381-387 %@ 03009831 %X The effect of dietary nucleotides at concentrations found in supplemented infant formula on P-glycoprotein (P-gp) expression in colon cells was examined. We report that P-gp expression in colon cells was significantly decreased in a time- and concentration-dependent manner. When colon cells were co-cultured with lymphocytes, so as to mimic the involvement of gut-associated lymphoid tissue in normal gut pathophysiology, we observed a reversal of this effect with a demonstrated increase in P-gp expression. These findings have important implications on effects of nucleotide exposure on increasing drug bioavailability, reducing the capacity for xenobiotic efflux, and increasing the risk of inflammatory bowel disease in susceptible infants. Future studies are directed at defining both the mechanisms underlying these findings and effects of dietary nucleotide supplementation in vivo. %Z FOR Codes: 1004 %0 Journal Article %~ PubMed %A Chua, Terence %A Yao, Peng %A Akther, Javed %A Young, Lawrence %A Bao, Shisan %A Samaraweera, Ushma %A Yan, Tristan %A Morris, David %T Differential Expression of Ki-67 and Sex Steroid Hormone Receptors Between Genders in Peritoneal Mesothelioma. %B Pathology oncology research : POR %D 2009 %C Netherlands %I Springer %V 15 %N 0 %P 671-8 %@ 1219-4956 %X Gender influence on survival in mesothelioma has been observed in several large clinical series. However, this gender effect has not been investigated. Female patients often have less aggressive tumors and survive longer. However, few studies in the literature have explained the molecular basis of this finding. Understanding this difference at a molecular level may offer the hope of improving survival via hormonal manipulation.We investigate the expression of Ki-67 and sex steroid receptors; estrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR) to elucidate any pathognomonic difference that characterize this gender difference. Positive expression of markers was observed in 95% (Ki-67), 80% (ER), 100% (PR) and 65% (AR) of patients. Expression of markers between gender showed a higher Ki-67 in males (M = 1.3%, F = 0.6%), higher estrogen receptor in females (M = 0.6%, F = 1.7%) and higher progesterone receptor in females (M = 1.0%, F = 1.4%). Twenty patients were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in our peritonectomy unit. Paraffin sections of the tumor specimens were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). For the first time, we demonstrate the presence of sex steroid receptors in peritoneal mesothelioma. Once the exact functional effects of these receptors are understood, the use of established therapeutic options that are clinically available to target the sex steroid pathway may become a reality. %Z FOR Codes: 30405 %0 Journal Article %~ PubMed %A Harris, Angie K %A Shen, Jie %A Radford, Jane %A Bao, Shisan %A Hambly, Brett D %T GM-CSF deficiency delays neointima formation in a normolipidemic mouse model of endoluminal endothelial damage. %B Immunology and cell biology %D 2009 %C United Kingdom %I Nature Publishing Group %V 87 %N 2 %P 122-30 %@ 1440-1711 %X Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been implicated in atherogenesis and has been shown to have both pro- and antiatherogenic properties. Neointimal thickening is a prominent feature of early atherogenesis. This study aimed to examine the role of GM-CSF in neointimal formation induced by endothelial injury using a GM-CSF(-/-) mouse model. Neointimal thickening was induced by endothelial damage in the common iliac arteries of normolipidemic C57Bl/6 (wild-type) and GM-CSF(-/-) mice. Arteries were collected weekly for 3-7 weeks following surgery. A significant delay in neointimal formation in the GM-CSF(-/-) compared with wild-type mice was detected by morphometric analysis of the intimal area. Neointimal size was approximately 10% smaller in GM-CSF(-/-) mice at 4-6 weeks post-surgery, compared with wild-type mice. The neointima was composed predominantly of smooth muscle cells and there was no difference in the extent of endothelial cell coverage between the wild-type and GM-CSF(-/-) mice. Using immunohistochemistry, reduced macrophages (F4/80(+) cells), proliferating cells (proliferating cell nuclear antigen (PCNA)(+) cells) and platelet-derived growth factor-B were detected within the arteries of GM-CSF(-/-) mice compared with wild types at 4 weeks post-surgery. GM-CSF(-/-) mice had reduced connective tissue within the neointima compared with wild types at 5 weeks post-surgery, determined by trichrome staining. We conclude that GM-CSF deficiency reduces neointimal formation in a normolipidemic model, primarily due to reduced macrophage recruitment. %Z FOR Codes: 110299 %0 Journal Article %~ PubMed %A Tan, Zi Yan %A Bealgey, Kenneth W %A Fang, Yong %A Gong, Yang Ming %A Bao, Shisan %T Interleukin-23: Immunological roles and clinical implications. %B The international journal of biochemistry & cell biology %D 2009 %C United Kingdom %I Pergamon %V 41 %N 4 %P 733-5 %@ 1357-2725 %X Increasing evidence has revealed the importance of IL-23, which closely resembles IL-12 both structurally and immunologically, in linking innate and adaptive immunity. IL-23, produced by activated type 1 macrophages and dendritic cells (DC), possesses unique roles in the differentiation and expansion of memory T cells. IL-23 has been associated with several inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (IBD) and Helicobacter pylori associated gastritis, mainly due to its capacity to induce a strong Th1 type immune response. IL-23 is also associated with Th17 responses and the cytokine produced by the antigen presenting cells (APC), i.e. IL-12 vs IL-23 determines in part if a response is Th1 or Th17. Recent studies have also associated chronic inflammatory diseases such as IBD, psoriasis and myocardial infarction with polymorphisms of the IL-23 receptor complex. The current review focuses on the immunological role of IL-23 and possible therapeutic avenues for inflammatory diseases. %Z FOR Codes: 110701 110316 %0 Journal Article %~ PubMed %A Xie, Qing %A Shen, Huai-Cheng %A Jia, Ni-Na %A Wang, Hui %A Lin, Lan-Yi %A An, Bao-Yan %A Gui, Hong-Lian %A Guo, Si-Min %A Cai, Wei %A Yu, Hong %A Guo, Qing %A Bao, Shisan %T Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9. %B Microbes and infection / Institut Pasteur %D 2009 %C France %I Elsevier %V 11 %N 0 %P 515-23 %@ 1286-4579 %X Chronic hepatitis B virus (HBV) infection is a complex interaction between replicating noncytopathic virus and dysregulatory host antiviral immunity. Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immunity via secreting type I interferons. Toll-like receptor (TLR) 9 is involved in major pattern recognition receptors expressed in pDCs. The frequency of pDCs and TLR9 expression in peripheral blood mononuclear cells (PBMC) was determined, using flow cytometry. IFN-alpha production by PBMC was evaluated in vitro in the presence of cytidine phosphate guanosine (CpG) with/without pDCs. The correlation between TLR9, pDCs frequency and viral load was also evaluated. TLR9 expression in pDCs in chronic HBV patients was significantly ( approximately 50%) reduced, supported by approximately 70% reduction of TLR9 mRNA, in comparison to healthy controls, correlating with the impairment of IFN-alpha production in vitro. Furthermore, pDCs frequency in these patients was substantially reduced ( approximately 30%), inversely correlating with serum ALT levels and HBV viral load. HBsAg and HBcAg were detected by immunohistochemistry in pDCs in chronic HBV patients. We conclude that HBV infection results in reduced frequency of circulating pDCs and their functional impairment via inhibiting the expression of TLR9. These data may provide useful information in both basic research and clinical treatment of chronic HBV infection. %Z FOR Codes: 110704 %0 Journal Article %~ PubMed %A Coon, C %A Beagley, K W %A Bao, S %T The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis. %B Scandinavian Journal of Immunology %D 2009 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 70 %N 2 %P 106-115 %@ 1365-3083 %X Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host''s immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80(+) effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host''s immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens. %Z FOR Codes: 60599 %0 Journal Article %~ PubMed %A Hickey, Danica K %A Aldwell, Frank E %A Tan, Zi Yan %A Bao, Shisan %A Beagley, Kenneth W %T Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection. %B Vaccine %D 2009 %C United Kingdom %I Elsevier Ltd %V 27 %N 50 %P 6983-6990 %@ 0264-410X %X The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system. %Z FOR Codes: 1103 %0 Journal Article %~ PubMed %A Zhang, Xinyuan %A Bao, Shisan %A Hambly, Brett D %A Gillies, Mark C %T Vascular endothelial growth factor-A: A multifunctional molecular player in diabetic retinopathy. %B The international journal of biochemistry & cell biology %D 2009 %C United Kingdom %I Pergamon %V 41 %N 12 %P 2368-71 %@ 1357-2725 %X Vascular endothelial growth factor-A (VEGF-A), first described as "vascular permeability factor", is a critical molecule in the pathogenesis of diabetic retinopathy at several levels. Previous studies have outlined the importance of VEGF-A in mediating vascular pathology in both experimental models and clinical diabetic retinopathy, which are characterized by retinal vascular leakage, preretinal neovascularisation and neuronal degeneration. Paradoxically, recent reports have emphasized the potential neurotrophic effects of VEGF-A on the quiescent vasculature, as well as its direct and indirect protective effects on retinal neurons. VEGF-A has also been identified as an important signalling regulator in the normal central nervous system. Consequently, anti-VEGF therapy for diabetic retinopathy has become a controversal issue. This review outlines recently developed concepts relating to the role of VEGF-A in the pathogenesis of diabetic retinopathy, with particular emphasis on its implications for clinical practice. %Z FOR Codes: 111301 %0 Journal Article %~ PubMed %A Zhang, Xinyuan %A Bao, Shisan %A Lai, Donna %A Rapkins, Robert W %A Gillies, Mark C %T Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier through Differential Regulation of VEGF-A and its Receptors in Early Diabetic Rat Retinas. %B Diabetes %D 2008 %C United States %I American Diabetes Association %V 57 %N 4 %P 1026-33 %@ 0012-1797 %X To elucidate the mechanism of the unique beneficial effect of intravitreal steroid therapy on diabetic macular edema, we investigated the effect of locally administered triamcinolone acetonide (TA) on the expression of vascular endothelial growth factor (VEGF)-A and its receptors in retinas of rats with streptozotocin (STZ)-induced diabetes. We then correlated the expression of these proteins with breakdown of the blood-retinal barrier (BRB). %Z FOR Codes: 111399 %0 Journal Article %~ PubMed %A Cunningham, Kelly A %A Carey, Alison J %A Finnie, Jane M %A Bao, Shisan %A Coon, Charmere %A Jones, Russell %A Wijburg, Odilia %A Strugnell, Richard A %A Timms, Peter %A Beagley, Kenneth W %T Poly-immunoglobulin receptor-mediated transport of IgA into the male genital tract is important for clearance of Chlamydia muridarum infection. %B American journal of reproductive immunology (New York, N.Y. : 1989) %D 2008 %C United States %I Wiley-Blackwell %V 60 %N 5 %P 405-14 %@ 1046-7408 %X PROBLEM: Chlamydia trachomatis is the most common sexually transmitted infection worldwide. While infection in females requires a Th1 response for clearance, such a response in males may disrupt the immune privileged nature of the male reproductive tract, potentially contributing to infertility. METHOD OF STUDY: We investigated the role of IgA in protection against an intrapenile Chlamydia muridarum infection of C57BL/6 and pIgR-/- mice. RESULTS: Here, we show that the poly immunoglobulin receptor is the main pathway for IgA transport into the male reproductive tract. The high levels of IgA seen in prostatic fluid of wild-type mice correlate with reduction in chlamydial infection both in vitro and in vivo. CONCLUSION: These findings indicate that a Chlamydia vaccine that induces neutralizing IgA in the prostate will aid in the protection against infection in males. %Z FOR Codes: 110704 %0 Journal Article %~ PubMed %A Sue, Nancy %A Jack, Briony H A %A Eaton, Sally A %A Pearson, Richard C M %A Funnell, Alister P W %A Turner, Jeremy %A Czolij, Robert %A Denyer, Gareth %A Bao, Shisan %A Molero-Navajas, Juan Carlos %A Perkins, Andrew %A Fujiwara, Yuko %A Orkin, Stuart H %A Bell-Anderson, Kim %A Crossley, Merlin %T Targeted disruption of the Basic Kruppel-like Factor (Klf3) gene reveals a role in adipogenesis. %B Molecular and cellular biology %D 2008 %C United States %I American Society for Microbiology %V 28 %N %P 3967-78 %@ 0270-7306 %X Kr??ppel-like factors (KLFs) recognize CACCC and GC-rich sequences in gene regulatory elements. Here, we describe the disruption of the murine basic Kr??ppel-like factor gene (Bklf or Klf3). Klf3 knockout mice have less white adipose tissue, and their fat pads contain smaller and fewer cells. Adipocyte differentiation is altered in murine embryonic fibroblasts from Klf3 knockouts. Klf3 expression was studied in the 3T3-L1 cellular system. Adipocyte differentiation is accompanied by a decline in Klf3 expression, and forced overexpression of Klf3 blocks 3T3-L1 differentiation. Klf3 represses transcription by recruiting C-terminal binding protein (CtBP) corepressors. CtBPs bind NADH and may function as metabolic sensors. A Klf3 mutant that does not bind CtBP cannot block adipogenesis. Other KLFs, Klf2, Klf5, and Klf15, also regulate adipogenesis, and functional CACCC elements occur in key adipogenic genes, including in the C/ebpalpha promoter. We find that C/ebpalpha is derepressed in Klf3 and Ctbp knockout fibroblasts and adipocytes from Klf3 knockout mice. Chromatin immunoprecipitations confirm that Klf3 binds the C/ebpalpha promoter in vivo. These results implicate Klf3 and CtBP in controlling adipogenesis. %Z FOR Codes: 1116 %0 Journal Article %~ PubMed %A Xu, Yinghua %A Hunt, Nicholas H %A Bao, Shisan %T The effect of restraint stress on experimental colitis is IFN-gamma independent. %B Journal of neuroimmunology %D 2008 %C Netherlands %I Elsevier BV %V 200 %N 0 %P 53-61 %@ 0165-5728 %X Stress, a protective reaction to external threats, may be deleterious if linked to an inflammatory stimulus. Stress may influence intestinal immunity, thereby contributing to the development of colitis. Less severe histological abnormalities and clinical scores were detected in dextran sulphate sodium (DSS)-induced colitis in IFN-gamma(-/-), compared to Wt, mice. Disease severity was increased by restraint stress in DSS-treated IFN-gamma(-/-) and Wt mice, accompanied by suppressed colonic pro and anti inflammatory cytokine responses. Our data suggest that IFN-gamma is important in the development of acute colitis. Stress increases the severity of colitis, but is independent of the IFN-gamma pathway. %Z FOR Codes: 110704 %0 Journal Article %~ PubMed %A Xu, Yinghua %A Hunt, Nicholas H %A Bao, Shisan %T The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation. %B Cell research %D 2008 %C United Kingdom %I Nature Publishing Group %V 18 %N 0 %P 1220-9 %@ 1748-7838 %X An imbalance of mucosal pro- and anti-inflammatory cytokines is crucial in the pathogenesis of inflammatory bowel disease (IBD). GM-CSF influences the development of hemopoietic cells. The precise role of GM-CSF in IBD remains to be elucidated. GM-CSF gene knockout (GM-CSF(-/-)) and wild-type (Wt) mice were challenged with 2.5% dextran sulfate sodium (DSS) for 7 days. The ensued clinical and pathological changes, macrophage infiltration, colonic cytokine production, and bacterial counts were examined. DSS-treated GM-CSF(-/-) mice developed more severe acute colitis than DSS-treated Wt mice, reflected by a greater body weight loss, more rectal bleeding, and aggravated histopathological changes. More infiltrating macrophages were observed in GM-CSF(-/-), compared with Wt mice following DSS challenge, correlating with monocyte chemoattractant protein-1 (MCP-1) production. The levels of colonic IL-17 and TNF-alpha were increased significantly in GM-CSF(-/-) mice, but not in Wt mice, following DSS administration. The level of IL-6 was increased by 1.5- and 2-fold in the colon of GM-CSF(-/-) and Wt mice, respectively, following DSS challenge. No significant changes in IL-4 and IFN-gamma were detected in Wt and GM-CSF(-/-) mice following DSS treatment. The bacteria recovery from colon was increased about 15- and 5-fold, respectively, in Wt mice and GM-CSF(-/-) mice following DSS challenge. These results suggest that GM-CSF(-/-) mice are more susceptible to acute DSS-induced colitis, possibly because of an impaired gut innate immune response as a result of diminished GM-CSF. %Z FOR Codes: 110701 %0 Journal Article %~ Isi %A Harris, AK %A Bao, S %A Hambly, BD %A Prabhu, KV %T Absence of toll-like receptor 4 increases macrophage population and collagen content in an endothelial denudation mouse model of neointimal proliferation %B ATHEROSCLEROSIS SUPPLEMENTS %D 2007 %C Ireland %I Elsevier Ireland Ltd %V 8 %N %P 229-229 %@ 1567-5688 %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Patel, Sanjay %A Celermajer, David S %A Bao, Shisan %T Atherosclerosis-Underlying inflammatory mechanisms and clinical implications. %B The international journal of biochemistry & cell biology %D 2007 %C United Kingdom %I Pergamon %V 40 %N 0 %P 576-80 %@ 1357-2725 %X Inflammation plays an important role in the initiation and progression of atherosclerosis but many of its underlying mechanisms remain to be explored. Atherosclerotic plaques which are more prone to destabilisation and rupture, leading to clinical events, are characterised by increased infiltration of leukocytes and other inflammatory mediators, compared with stable fibrotic plaques. T cell mediated responses, through expression of cytokines and chemokines, play an important role in the inflammatory process; and more recently potentially anti-inflammatory markers have also been identified. Current management involves both mechanical restoration of blood flow and pharmacotherapy aimed in part at suppressing the underlying inflammatory mechanisms. The aims of this review are to outline the pro- and anti-inflammatory processes in atherosclerosis, as well as their clinical implications. %Z FOR Codes: %0 Journal Article %~ PubMed %A Tavakoli, Nasim Nik %A Hambly, Brett D %A Sullivan, David R %A Bao, Shisan %T Forkhead box protein 3: Essential immune regulatory role. %B The international journal of biochemistry & cell biology %D 2007 %C United Kingdom %I Pergamon %V 40 %N 0 %P 2369-73 %@ 1357-2725 %X CD4+CD25+ regulatory T (Treg) cells play a crucial role in maintaining self-tolerance and preventing autoimmune disease. The transcription factor forkhead box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells. Foxp3 is highly expressed in lymphoid tissue and several signalling pathways influence its expression. It plays an essential role in the development and function of Treg cells. Mutations in Foxp3 are responsible for the scurfy (sf) mutant mouse, and for autoimmune human diseases including the X-linked fatal "immune dysregulation, polyendocrinopathy, enteropathy, X-linked" (IPEX), autoimmune colitis and rheumatoid arthritis. Recent studies have also revealed an important and novel anti-atherogenic role for Treg cells and consequently for Foxp3. These data open up potential novel therapeutic avenues for the management of atherosclerosis. %Z FOR Codes: 110704 %0 Journal Article %~ Isi %A Fang, Y %A Bao, S %A Hambly, BD %A Gong, SJ %A Xu, YH %T Impaired cutaneous wound healing in granulocyte/macrophage colony-stimulating factor knockout mice %B BRITISH JOURNAL OF DERMATOLOGY %D 2007 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 157 %N 3 %P 458-465 %@ 0007-0963 %X %Z FOR Codes: 110702 %0 Journal Article %~ Isi %A Bao, S %A Hambly, BD %A Harris, AK %A Tavakoli, NN %T Interferon-gamma contributes to neointimal proliferation following arterial angioplasty in a mouse model %B ATHEROSCLEROSIS SUPPLEMENTS %D 2007 %C Ireland %I Elsevier Ireland Ltd %V 8 %N %P 65-66 %@ %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Pearson, Richard %A Fleetwood, Jacqueline %A Eaton, Sally %A Crossley, Merlin %A Bao, Shisan %T Kruppel-like transcription factors: A functional family. %B The international journal of biochemistry & cell biology %D 2007 %C United Kingdom %I Pergamon %V 40 %N 0 %P 1996-2001 %@ 1357-2725 %X The Kr??ppel-like factor (Klfs) family of gene regulatory proteins are transcription factors implicated in many biological processes, including proliferation, apoptosis, differentiation and development. The characteristic feature of this family is the presence of three Kr??ppel-like zinc fingers, which bind to CACCC elements and GC-rich regions of DNA, to mediate activation and/or repression of transcription. In recent years several Klf knockout mice have been generated. The aim of this review is to outline the biological roles of those Klfs as deduced from the gene ablation studies. %Z FOR Codes: 110106 %0 Journal Article %~ PubMed %A Puranik, Rajesh %A Bao, Shisan %A Nobecourt, Estelle %A Nicholls, Stephen J %A Dusting, Gregory J %A Barter, Philip J %A Celermajer, David S %A Rye, Kerry-Anne %T Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo. %B Atherosclerosis %D 2007 %C Ireland %I Elsevier Ireland Ltd %V 196 %N 0 %P 240-7 %@ 0021-9150 %X This study investigates the ability of a single, low dose of apolipoprotein (apo) A-I, the main lipoprotein of high density lipoproteins (HDL), to inhibit acute vascular inflammation in normocholesterolemic New Zealand White rabbits. Acute vascular inflammation was induced in the animals by placing a non-occlusive, silastic collar around the left common carotid artery. The animals (n=5/group) received a single, low dose infusion of saline or lipid-free apoA-I at the time of, or 3 or 9h after collar insertion. The animals were sacrificed 24h post-collar insertion. Inflammatory markers in the artery wall were quantitated immunohistochemically. The saline-treated animals exhibited substantial pan-arterial inflammation, which was inhibited by a single apoA-I infusion (2 or 8 mg/kg) at the time of collar insertion. A single 8 mg/kg infusion of lipid-free apoA-I administered 3h post-collar insertion reduced neutrophil recruitment into the vessel wall, and MPO expression, as well as endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by >85% (p<0.01 for all). A single 8 mg/kg infusion of lipid-free apoA-I administered 9h after collar insertion decreased VCAM-1 expression, neutrophil infiltration and MPO expression by 88% (p<0.001), 47% (p<0.01), and 90% (p<0.01), respectively. This indicates that a single low dose infusion of apoA-I administered after the onset of acute inflammation in carotid arteries decreases neutrophil infiltration and inhibits neutrophil and endothelial cell activation. These findings have potential implications for treating acute vascular inflammation in conditions such as acute coronary and stroke syndromes. %Z FOR Codes: 110104 %0 Journal Article %~ Isi %A Lu, SY %A Dai, W %A Bao, SS %A Chen, Z %A Chen, SJ %A Lu, ZY %A Li, XH %A Kong, H %A Wang, ZG %A Wang, L %A Liu, XS %A Liu, ZX %A Sun, YP %A Zhang, HX %A Wang, Y %A Liu, QL %T Rig-I-/- mice develop colitis associated with downregulation of G alpha i2 %B CELL RESEARCH %D 2007 %C United Kingdom %I Nature Publishing Group %V 17 %N 10 %P 858-868 %@ 1001-0602 %X %Z FOR Codes: 110702 %0 Journal Article %~ PubMed %A Xu, Yinghua %A Hunt, Nicholas H %A Bao, Shisan %T The correlation between proinflammatory cytokines, MAdCAM-1 and cellular infiltration in the inflamed colon from TNF-alpha gene knockout mice. %B Immunology and cell biology %D 2007 %C UK, Australia %I Nature Publishing Group %V 85 %N 8 %P 633-9 %@ 1440-1711 %X Tumour necrosis factor (TNF) is important in the development of inflammatory bowel disease. TNF-alpha-deficient mice show more severe colonic inflammation than wild-type (Wt) mice, but the underlying mechanism remains unclear. Using immunohistochemistry, enzyme-linked-immunosorbent assay and histopathology, we found that there was a higher level of macrophage infiltration in TNF-alpha(-/-) compared to Wt mice. This is consistent with higher levels of monocyte chemotactic protein-1, interleukin (IL)-6 and granulocyte monocyte colony-stimulating factor (GM-CSF) in the inflamed colon from the TNF-alpha(-/-) mice, compared to the Wt mice, following dextran sulphate sodium (DSS) challenge. There was close correlation between clinical observations and histopathological findings in both Wt and TNF-alpha(-/-) mice. The expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in the colon of Wt and TNF-alpha(-/-) mice following DSS challenge. Interestingly, the induction of MAdCAM-1 was relatively lower in the inflamed colon of TNF-alpha(-/-) mice, despite the higher inflammatory cell infiltrate, compared to their Wt counterparts. On the other hand, TNF-alpha(-/-) mice had significantly lower baseline levels of colonic IL-4, IL-6 and GM-CSF. Furthermore, there was a reduction of both immunoglobulin A (IgA) and IgG in the gut from TNF-alpha(-/-) mice following DSS challenge. These data indicate that TNF-alpha deficiency alters homoeostasis of the colonic chemokine/cytokine environment and humoral immune response, resulting in an exacerbation of acute DSS-induced colitis in TNF-alpha(-/-) mice. These findings support the idea that TNF-alpha plays a role in the acute stage of intestinal inflammation. %Z FOR Codes: 110316 %0 Journal Article %~ Isi %A Mei, Y %A Bao, S %A Xu, L %A Wang, Y %T Vasoactive intestinal polypeptide enhances oral tolerance by regulating both cellular and humoral immune responses %B CLINICAL AND EXPERIMENTAL IMMUNOLOGY %D 2007 %C United States %I Wiley-Blackwell Publishing Ltd. %V 148 %N 1 %P 178-187 %@ 0009-9104 %X %Z FOR Codes: 110702