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Jie Xiong,
Jianbo Ni,
Guoyong Hu,
Jie Shen,
Yan Zhao,
Lijuan Yang,
Jiaqing Shen,
Guojian Yin,
Congying Chen,
Ge Yu,
Yanling Hu,
Miao Xing,
Wan Rong, Xingpeng Wang
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ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Shikonin, a highly liposoluble naphthoquinone pigment isolated from the traditional medical herbs Lithospermum erythrorhizon (LE), was considered to exhibit an anti-inflammatory property. While the potential of shikonin to ameliorate acute pancreatitis (AP) is unknown. Our aim was to investigate the effects of shikonin in a murine model of cerulein-induced pancreatitis. MATERIALS AND METHODS: AP was induced in mice by 6 intraperitoneal injection of cerulein (50µg/kg) at hourly intervals. Vehicle or shikonin (50mg/kg) was pretreated 2h before the first cerulein injection. After 6h, 9h and 12h of the first cerulein injection, the severity of acute pancreatitis was assessed by biochemistry, myeloperoxidase activity, histological grading, proinflammatory cytokines levels and nuclear factor kappa B (NF-κB) activity. RESULTS: Shikonin administration significantly reduced serum amylase and lipase activities, pancreatic histological scores, TNF-α, IL-1β, IL-6 levels, MPO activity and NF-κB activity. CONCLUSION: Taken together, these results suggest that shikonin might protect against experimental pancreatitis by reducing release of inflammatory cytokines via inhibition of NF-κB activity.The therapeutic role of shikonin in AP needs futher investigation.
Journal of ethnopharmacology 11/2012; · 2.32 Impact Factor
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Jianbo Ni,
Guoyong Hu,
Jie Xiong,
Jie Shen,
Jiaqing Shen,
Lijuan Yang,
Maochun Tang,
Yan Zhao,
Guojian Ying,
Ge Yu,
Yanling Hu,
Miao Xing,
Rong Wan, Xingpeng Wang
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ABSTRACT: Interleukin (IL)-17A is a proinflammatory cytokine, which has recently attracted much interest due to its pathogenic role in various inflammatory conditions such as ischemia/reperfusion injury, chronic inflammation, and autoimmune diseases, but the role of IL-17A in acute pancreatitis remains unclear. This study aimed to investigate the role of IL-17A in experimental acute necrotizing pancreatitis (ANP). We analyzed the expression of IL-17A during the pathogenesis of ANP in vivo induced by 3 % sodium taurocholate (NaTc), by microarray test, quantitative real-time PCR, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. The effects of IL-17A on pancreatic acinar cells and pancreatic stellate cells (PSCs) were further investigated in vitro using recombinant rat IL-17A (rIL-17A). Expression of IL-17A was significantly increased following experimental acute pancreatitis. In addition, rIL-17A induced rat pancreatic acinar cell necrosis and promoted expression of several target genes, including IL-6, IL-1β, CXCL1, CXCL2, and CXCL5, in acinar cells and PSCs. These findings suggest that IL-17A may be involved in pancreatic damage by regulating the expression of inflammatory cytokines and chemokines during experimental acute pancreatitis.
Inflammation 09/2012; · 1.75 Impact Factor
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ABSTRACT: BACKGROUND: Visceral hypersensitivity is an important etiology of non-erosive reflux disease (NERD). Calcitonin gene-related peptide (CGRP) and substance P (SP) are involved in the sensitization of afferent neuronal pathways. AIM: The objectives of this study were to evaluate visceral hypersensitivity in NERD patients, investigate the association between visceral hypersensitivity and mucosal expression of SP and CGRP, and assess their involvement in the pathogenesis of NERD. METHODS: Twenty-six NERD patients and 12 healthy volunteers were recruited. Intraesophageal balloon distention was performed, and initial perception threshold (IPT) and threshold of discomfort (ToD) were determined. Immunohistochemical staining was used to measure the optical density (OD) of CGRP and SP-reactive levels in esophageal mucosa, and the numbers of CGRP and SP-reactive neural fibers. RESULTS: IPT and ToD were 9.6 ± 4.8 and 12.3 ± 3.2 ml, respectively, in NERD patients, significantly lower than for controls (13.2 ± 7.5 and 21.6 ± 5.7 ml, P < 0.05 and P < 0.01, respectively). Mean OD values for CGRP and SP staining were significantly higher in NERD than for controls (both P < 0.05) and, in NERD, were negatively correlated with IPT and ToD (all P < 0.01). Numbers of CGRP and SP-reactive neural fibers in esophageal submucosa of NERD patients were significantly increased (both P < 0.05). CONCLUSIONS: Expression of esophageal epithelial CGRP and SP is increased, and correlates negatively with perception thresholds in NERD. These findings may aid understanding of peripheral visceral hypersensitivity and the development of new therapeutic approaches for management of NERD.
Digestive Diseases and Sciences 09/2012; · 2.12 Impact Factor
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Guoyong Hu,
Yan Zhao,
Yin Tang,
Yuhui Wang,
Jie Shen,
Lu Liu,
Haibo Li,
Yahan Liu,
Xin Cui,
Yongchun Yu,
Chuanyong Guo, Xingpeng Wang,
George Liu
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ABSTRACT: The aim of the present study was to develop a model of hypertriglyceridemic (HTG) acute pancreatitis and to investigate the effects of probucol in this model.
Hamsters were fed a high-fat diet (HFD) or a normal diet for 3 weeks. Probucol was added at 1% to the HFD in the treated group. Pancreatitis was induced by 7 peritoneal injections of cerulein to the normal and HFD hamster groups. The severity of the pancreatitis and whole body oxidative stress were assessed.
The HFD induced severe HTG (>1000 mg/dL) in the hamsters. A more severe pancreatitis was observed in the HFD group. The HFD did not influence plasma-reduced glutathione level, but there was a significant increase after 1% probucol was provided in the diet. Plasma malonaldehyde levels in the HFD group were significantly higher than the normal chow group, whereas probucol administration significantly decreased plasma hydrogen peroxide and malonaldehyde levels. We also found that probucol significantly reduced levels of amylase and lipase in the plasma and pathological scores in pancreatic tissue.
This study presents a novel model of severe HTG acute pancreatitis, and our results support the potential therapeutic application of probucol in HTG acute pancreatitis.
Pancreas 08/2012; 41(6):845-8. · 2.39 Impact Factor
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ABSTRACT: Thrombopoietin (TPO) plays an important role in injuries of different tissues. However, the role of TPO in acute pancreatitis (AP) is not yet known. The aim of the study was to determine the involvement of TPO in AP. Serum TPO was assayed in necrotizing pancreatitis induced by L-arginine in mice. Recombinant TPO and anti-TPO antibody were given to mice with necrotizing pancreatitis. Amylase, lipase, lactate dehydrogenase, myeloperoxidase activity and pancreatic water content were assayed in serum and tissue samples. Pancreas and lung tissue samples were also collected for histological evaluation. Immunohistochemistry of amylase α and PCNA were applied for the study of acinar regeneration and TUNEL assay for the detection of apoptosis in the pancreas. Increased levels of serum TPO were found in necrotizing pancreatitis. After TPO administration, more severe acinar necrosis was found and blockade of TPO reduced the acinar necrosis in this AP model. Acinar regeneration and apoptosis in the pancreas were affected by TPO and antibody treatment in necrotizing pancreatitis. The severity of pancreatitis-associated lung injury was worsened after TPO treatment, but attenuated after Anti-TPO antibody treatment. In conclusion, serum TPO is up-regulated in the necrotizing pancreatitis induced by L-arginine in mice and may be a risk factor for the pancreatic acinar necrosis in AP. As a pro-necrotic factor, blockade of TPO can attenuate the acinar necrosis in AP and may be a possible therapeutic intervention for AP.
Cytokine 06/2012; 60(1):294-301. · 3.02 Impact Factor
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ABSTRACT: The objective of this study was to assess pancreatic exocrine function (PEF) and morphology in patients recovering from a first episode of acute pancreatitis (AP).
Sixty-five eligible patients recovering from AP and 70 healthy volunteers were enrolled in this study. We evaluated PEF by fecal elastase 1 (FE-1) and used ultrasonography to detect pancreatic morphology for all patients and 40 controls.
Exocrine pancreatic insufficiency (EPI) incidence in the severe and mild AP subgroups was 60.5% and 39.5%, respectively. The FE-1 level in patients who had undergone surgical care was significantly lower compared with the controls (P < 0.01), whereas no difference was observed between the alcoholic and nonalcoholic groups (P > 0.05). Surprisingly, the defecation change correlated with the EPI level. In these patients, a stepwise recovery was observed over the following 2.4 years. Compared with the controls, the diameter of pancreatic duct was enlarged, and abdominal pain during recovery was found to be the independent risk factor for pancreatic duct expansion, although a significant difference was not exhibited between the AP subgroups concerning FE-1 concentration (P = 0.591).
Our results indicated that many AP patients may have long-lasting EPI and an expanded main pancreatic duct; thus, routine evaluation of PEF is warranted.
Pancreas 04/2012; 41(6):922-7. · 2.39 Impact Factor
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ABSTRACT: Acute pancreatitis is a common disease, which is divided into mild pancreatitis and severe pancreatitis. For the latter, a systemic inflammatory response may occur and lead to distant organ damage and the development of multiple organ dysfunction syndrome (MODS), which accounts for significant morbidity and mortality in humans. Chemokines and their receptors are being believed to play a pivotal role in the pathogenesis of acute pancreatitis. Chemokine receptor CXCR3 is reported to be involved in acute tissue injury, for example acute lung injury induced by cigarette smoking, but its role in acute pancreatitis is not yet known. In this study, two animal models of acute pancreatitis (cerulein- and arginine-induced pancreatitis) were applied in CXCR3⁻/⁻ mice and wild-type mice, in order to explore the role of CXCR3 in acute pancreatitis. Serum amylase, lipase and histological observations revealed that CXCR3 knockout did not affect the severity of acute pancreatitis. However, edema and inflammatory cell infiltrate in the lung tissue were attenuated in CXCR3⁻/⁻ mice when acute pancreatitis was induced. In conclusion, chemokine receptor CXCR3 is not involved in acute pancreatic injury, but has a connection with acute pancreatitis-associated lung injury. Acute pulmonary injury is attenuated in CXCR3 knockout mice in experimental acute pancreatitis.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 03/2012; 66(5):390-6. · 2.24 Impact Factor
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ABSTRACT: Background/Aims: Endoplasmic reticulum (ER) stress and hypertriglyceridemia (HTG) have been implicated in acute pancreatitis (AP). Methodology: For cellular model, rat exocrine acinar cells were preincubated with palmitic acid (0.05 or 0.1mmol/L, 3h) and stimulated with a cholecystokinin analog, CCK-8 (100pmol/L, 30min). For animal model, rats fed a high-fat diet to cause HTG and AP was induced by injection of caerulein (20µg/kg). Injury to pancreatic cells was estimated by measuring amylase secretion, intracellular calcium concentration, apoptosis and histological changes. Expression of genes involved in ER stress-induced unfolded protein response (UPR) was monitored by RT-PCR and immunohistology. Results: In CCK-8 stimulated rat acinar cells, preincubation with PA caused an increased secretion of amylase, a higher and prolonged accumulation of intracellular calcium and increased apoptosis. Rats on high-fat diet had significantly elevated serum triglyceride levels. Induction of AP led to increased apoptosis in pancreatic tissue on high-fat diet than controls. For favoring HTG, expression of UPR components, GRP78/Bip, XBP-1, GADD153/CHOP and caspase-12 was upregulated. Conclusions: Levels of markers of AP pathogenesis and components of UPR were elevated in the presence of excess fatty acids in pancreatic acinar cells. HTG appears to aggravate ER-stress and pathogenesis of AP.
Hepato-gastroenterology 03/2012; 59(119). · 0.66 Impact Factor
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Jie Shen,
Rong Wan,
Guoyong Hu,
Lijuan Yang,
Jie Xiong,
Feng Wang,
Jiaqing Shen,
Shanshan He,
Xiaoyan Guo,
Jianbo Ni,
Chuanyong Guo, Xingpeng Wang
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ABSTRACT: Activated pancreatic stellate cells (PSCs) play a pivotal role in the development of pancreatic diseases, especially chronic pancreatitis and pancreatic cancer. MicroRNAs have become a focal point of interest as post-transcriptional regulators of gene expression via their interaction with the 3' untranslated region of target mRNAs, which results in gene silencing. We examined the relative expression of microRNAs (miR-15b and miR-16) and their target gene, Bcl-2, during activation of rat PSCs, and determined their effects on apoptosis of rat PSCs in vitro.
miR-15b and miR-16 expression levels were analyzed in quiescent and activated PSCs by stem-loop RT-PCR. In addition, the effects of miR-15b and miR-16 on apoptosis of activated PSCs were investigated by immunofluorescence microscopy with Hoechst 33342 staining, and flow cytometry with annexin-V/propidium (PI) co-labeling. Bcl-2 and Bcl-xl were also analyzed by real-time RT-PCR and Western blotting.
During activation of PSCs, from the quiescent stage to activated stage, miR-15b and miR_16 were downregulated, while Bcl-2 expression was upregulated. Restoring intracellular miRNA levels by miR-15b and miR-16 administration greatly reduced Bcl-2 protein levels, and significantly induced apoptosis in activated PSCs.
miR-15b and miR-16 could induce apoptosis of rat PSCs by targeting Bcl-2.
Pancreatology 03/2012; 12(2):91-9. · 1.99 Impact Factor
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Jiaqing Shen,
Jing Gao,
Jing Zhang,
Di Xiang,
Xia Wang,
Lan Qian,
Jie Shen,
Lijuan Yang,
Shunying Zhu,
Mingyuan Wu,
Yan Yu,
Wei Han, Xingpeng Wang
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ABSTRACT: Chronic pancreatitis is a progressive inflammatory disease featuring irreversible irregular scarring of the exocrine parenchyma characterized by acinar destruction and fibrosis subsequent to inflammation in the pancreas. Despite decades of research, the knowledge is limited to the treatment of this disease. After finding a connection between interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) in caerulein-induced chronic pancreatitis, we assumed that recombinant human IL-1Ra (rhIL-1Ra), the natural antagonist of IL-1β, might have a protective role in chronic pancreatitis in mice. Chronic pancreatitis was induced by repetitive intraperitoneal injections of caerulein in C57/BL mice followed by a consecutive administration of rhIL-1Ra (10mg/kg). Collagen content and histological changes in the pancreas as well as serum amylase and lipase were measured. We found that rhIL-1Ra significantly decreased the hydroxyproline and the fibrotic area in the pancreas after the caerulein challenge. Caerulein-induced serum amylase elevation and tissue damage were also attenuated in rhIL-1Ra treated mice. Our results reveal a potential role of rhIL-1Ra in protecting mice against caerulein-induced chronic pancreatitis and lead to a conclusion that this protein may be a potential candidate agent for the treatment of chronic pancreatitis in humans.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 01/2012; 66(2):83-8. · 2.24 Impact Factor
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ABSTRACT: To investigate the effect and possible mechanisms of resveratrol on pancreatic cancer cells in vitro.
After being treated with resveratrol, cell viability, cell cycle phase distribution and apoptosis rate of pancreatic cancer cells were measured by CCK-8 assay and flow cytometer, respectively. The effects of resveratrol on the Hedgehog pathway were studied by real-time RT-PCR and Western blotting. By interfering Gli1 expression in PANC-1 cells and overexpressing Gli1 in BxPC-3 cells, we detected the expressions of Gli1-targeted genes, such as Ptc1, CCND1 and BCL-2, compared with resveratrol experimental group. We further used the luciferase reporter assay to explore the correlation between resveratrol and Gli1.
Resveratrol inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. Compared with control group, the cells in the G0/G1 phase and the apoptosis rate were significantly increased. Low concentration of resveratrol decreased the expression of the Hedgehog pathway members including Gli1, Ptc1 and Smo. The expression of downstream target genes of the Hedgehog pathway such as Gli1, Ptc1, CCND1 and BCL-2 were significantly decreased after 12.5 μM resveratrol treatment, which demonstrated a similar change of gene expression when Gli1 was knocked down by the RNAi technique in PANC-1 cells. Resveratrol also downregulated the expression of Gli1, Ptc1, CCND1 and BCL-2 in Gli1-overexpressed BxPC-3 cells. Results of the luciferase assay showed that resveratrol did not act on the Gli1 promoter directly.
Resveratrol can inhibit pancreatic cancer cell survival and its mechanisms might be partly via the Hedgehog signaling pathway. and IAP.
Pancreatology 01/2012; 11(6):601-9. · 1.99 Impact Factor
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LiJuan Yang,
JiaQing Shen,
ShanShan He,
GuoYong Hu,
Jie Shen,
Feng Wang,
Ling Xu,
WeiQi Dai,
Jie Xiong,
JianBo Ni,
ChuanYong Guo,
Rong Wan, XingPeng Wang
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ABSTRACT: Recent studies have shown that activated pancreatic stellate cells (PSCs) play a major role in pancreatic fibrogenesis. We aimed to study the effect of L-cysteine administration on fibrosis in chronic pancreatitis (CP) induced by trinitrobenzene sulfonic acid (TNBS) in rats and on the function of cultured PSCs.
CP was induced by TNBS infusion into rat pancreatic ducts. L-cysteine was administrated for the duration of the experiment. Histological analysis and the contents of hydroxyproline were used to evaluate pancreatic damage and fibrosis. Immunohistochemical analysis of α-SMA in the pancreas was performed to detect the activation of PSCs in vivo. The collagen deposition related proteins and cytokines were determined by western blot analysis. DNA synthesis of cultured PSCs was evaluated by BrdU incorporation. We also evaluated the effect of L-cysteine on the cell cycle and cell activation by flow cytometry and immunocytochemistry. The expression of PDGFRβ, TGFβRII, collagen 1α1 and α-SMA of PSCs treated with different concentrations of L-cysteine was determined by western blot. Parameters of oxidant stress were evaluated in vitro and in vivo. Nrf2, NQO1, HO-1, IL-1β expression were evaluated in pancreas tissues by qRT-PCR.
The inhibition of pancreatic fibrosis by L-cysteine was confirmed by histological observation and hydroxyproline assay. α-SMA, TIMP1, IL-1β and TGF-β1 production decreased compared with the untreated group along with an increase in MMP2 production. L-cysteine suppressed the proliferation and extracellular matrix production of PSCs through down-regulating of PDGFRβ and TGFβRII. Concentrations of MDA+4-HNE were decreased by L-cysteine administration along with an increase in GSH levels both in tissues and cells. In addition, L-cysteine increased the mRNA expression of Nrf2, NQO1 and HO-1 and reduced the expression of IL-1β in L-cysteine treated group when compared with control group.
L-cysteine treatment attenuated pancreatic fibrosis in chronic pancreatitis in rats.
PLoS ONE 01/2012; 7(2):e31807. · 4.09 Impact Factor
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Xuanfu Xu,
Yingqun Zhou,
Chuangao Xie,
Shu-mei Wei,
Huizhong Gan,
Shengli He,
Fan Wang,
Ling Xu,
Jie Lu,
Weiqi Dai,
Lei He,
Ping Chen, Xingpeng Wang,
Chuanyong Guo
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ABSTRACT: The role of sonic hedgehog (SHH) in epithelial mesenchymal transition (EMT) of pancreatic cancer (PC) is known, however, its mechanism is unclear. Because SHH promotes tumor development predominantly through Gli1, we sought to understand its mechanism by identifying Gli1 targets in pancreatic cancer cells.
First, we investigated invasion, migration, and EMT in PC cells transfected with lentiviral Gli1 interference vectors or SHH over-expression vectors in vitro and in vivo. Next, we determined the target gene profiles of Gli1 in PC cells using cDNA microarray assays. Finally, the primary regulatory networks downstream of SHH-Gli1 signaling in PC cells were studied through functional analyses of these targets.
Our results indicate there is decreased E-cadherin expression upon increased expression of SHH/Gli1. Migration of PC cells increased significantly in a dose-dependent manner within 24 hours of Gli1 expression (P<0.05). The ratio of liver metastasis and intrasplenic miniature metastasis increased markedly upon activation of SHH-Gli1 signals in nude mice. Using cDNA microarray, we identified 278 upregulated and 59 downregulated genes upon Gli1 expression in AsPC-1 cells. The data indicate that SHH-Gli1 signals promote EMT by mediating a complex signaling network including TGFβ, Ras, Wnt, growth factors, PI3K/AKT, integrins, transmembrane 4 superfamily (TM4SF), and S100A4.
Our results suggest that targeting the molecular connections established between SHH-Gli1 signaling and EMT could provide effective therapies for PC.
PLoS ONE 01/2012; 7(8):e43119. · 4.09 Impact Factor
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ABSTRACT: The enterocytes have the potential to absorb noxious substances, such as microbial products, from the gut lumen. How the enterocytes process the substances to harmless materials is not fully understood. This study aims to elucidate the role of ubiquitin E3 ligase TNFAIP3 (TNFAIP3) in facilitating the degradation of endocytic microbial products in enterocytes.
Human intestinal epithelial cell line, HT-29 cells, was cultured to monolayers using as an in vitro model to observe the endocytosis and degradation of microbial products, Staphylococcal enterotoxin B (SEB) in epithelial cells. The RNA interference was employed to knock down the TNFAIP3 gene in HT-29 cells to observe the role of TNFAIP3 in the degradation of endocytic SEB. The role of TNFAIP3 in facilitating the endosome/lysosome fusion was observed by immunocytochemistry.
Upon the absorption of SEB, the expression of TNFAIP3 was increased in HT-29 cells. Silencing the TNFAIP3 gene in HT-29 cells resulted in a large quantity of SEB to be transported across the HT-29 monolayers to the transwell basal chambers; the transportation was via the intracellular pathway. TNFAIP3 was required in the fusion of SEB-carrying endosomes and lysosomes.
TNFAIP3 plays a critical role in the degradation of endocytic SEB in enterocytes.
PLoS ONE 01/2012; 7(9):e45941. · 4.09 Impact Factor
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Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 11/2011; 10(3):e21-2. · 5.64 Impact Factor
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ABSTRACT: This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP).
Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated.
Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time.
Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.
Pancreas 06/2011; 40(7):1006-11. · 2.39 Impact Factor
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Feng Wang,
Ling Xu,
Chuanyong Guo,
Aiwu Ke,
Guoyong Hu,
Xuanfu Xu,
Wenhui Mo,
Lijuan Yang,
Yinshi Huang,
Shanshan He, Xingpeng Wang
PLoS ONE 01/2011; 6(4). · 4.09 Impact Factor
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Zhanju Liu,
Praveen K Yadav,
Xiaorong Xu,
Jingling Su,
Chi Chen,
Maochun Tang,
Hui Lin,
Jifeng Yu,
Jiaming Qian,
Ping-Chang Yang, Xingpeng Wang
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ABSTRACT: This study analyzed IL-23p19 expression in inflamed mucosa of IBD and the role in the induction of IEL and NK cell activation as well as Th17 cell differentiation. Expression of IL-23p19 was performed by immunohistochemistry and quantitative real-time PCR. Expression of IL-23R was assessed by flow cytometry. Cytolytic activities of IEL and NK cells by IL-23 were determined by a standard (51)Cr-release assay. Cytokine levels were analyzed by ELISA and quantitative real-time PCR. Expression of IL-23p19 was increased significantly in inflamed mucosa of CD compared with that in UC and healthy controls. Double-staining confirmed that IL-23p19(+) cells were mainly CD68(+) macrophages/DCs. IL-23R(+) cells were increased significantly in PB- and LP-CD4(+) and -CD8(+) T and NK cells. IL-23 markedly promoted IBD IEL and NK cell activation and cytotoxicity and triggered IBD PB- and LP-T cells to secrete significantly higher levels of IFN-γ, TNF, IL-2, and IL-17A compared with controls. Importantly, IL-23 promoted IBD PB- or LP-CD4(+) T cells to differentiate into Th17 cells, characterized by increased expression of IL-17A and RORC. Anti-TNF treatment could markedly reduce IL-23 expression and Th17 cell infiltration in inflamed mucosa of CD patients. These data indicate that IL-23 is highly expressed in inflamed mucosa of IBD and plays an important role in the induction of IEL, NK, and T cell activation, proinflammatory cytokine secretion, and Th17 cell differentiation. Targeted therapy directed against IL-23p19 may have a therapeutic role in treatment of IBD.
Journal of leukocyte biology 01/2011; 89(4):597-606. · 4.99 Impact Factor
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ABSTRACT: Objective. To analyze the effect of total parenteral nutrition (TPN) and enteral nutrition (EN) in patients with acute pancreatitis. Methods. Randomized controlled trials of TPN and EN in patients with acute pancreatitis were searched in NCBI and CBM databases and The Cochrane Controlled Trials Register. Six studies were enrolled into the analysis, and the details about the trial designs, characters of the subjects, results of the studies were reviewed by two independent authors and analyzed by STATA 11.0 software. Results. Compared with TPN, EN was associated with a significantly lower incidence of pancreatic infection complications (RR = 0.556, 95% CI 0.436∼0.709, P = .000), MOF (RR = 0.395, 95% CI 0.272∼0.573, P = .003), surgical interventions (RR = 0.556, 95% CI 0.436∼0.709, P = .000), and mortality (RR = 0.426, 95% CI 0.238∼0.764, P = .167). There was no statistic significance in non-pancreatitis-related complications (RR = 0.853, 95% CI 0.490∼1.483, P = .017). However, EN had a significantly higher incidence of non-infection-related complications (RR = 2.697, 95% CI 1.947∼3.735, P = .994). Conclusion. EN could be the preferred nutrition feeding method in patients with acute pancreatitis.
Gastroenterology Research and Practice 01/2011; 2011:698248. · 0.98 Impact Factor
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ShanShan He,
Feng Wang,
LiJuan Yang,
ChuanYong Guo,
Rong Wan,
AiWu Ke,
Ling Xu,
GuoYong Hu,
XuanFu Xu,
Jie Shen, XingPeng Wang
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ABSTRACT: GLI1, as an indispensable transcriptional factor of Hedgehog signaling pathway, plays an important role in the development of pancreatic cancer (PC). DNA methyltransferases (DNMTs) mediate the methylation of quantity of tumor-related genes. Our study aimed to explore the relationship between GLI1 and DNMTs.
Expressions of GLI1 and DNMTs were detected in tumor and adjacent normal tissues of PC patients by immunohistochemistry (IHC). PANC-1 cells were treated by cyclopamine and GLI1-siRNA, while BxPC-3 cells were transfected with overexpression-GLI1 lentiviral vector. Then GLI1 and DNMTs expression were analyzed by qRT-PCR and western blot (WB). Then we took chromatin immunoprecipitation (ChIP) to demonstrate GLI1 bind to DNMT1. Finally, nested MSP was taken to valuate the methylation levels of APC and hMLH1, when GLI1 expression altered.
IHC result suggested the expressions of GLI1, DNMT1 and DNMT3a in PC tissues were all higher than those in adjacent normal tissues (p<0.05). After GLI1 expression repressed by cyclopamine in mRNA and protein level (down-regulation 88.1±2.2%, 86.4±2.2%, respectively), DNMT1 and DNMT3a mRNA and protein level decreased by 91.6%±2.2% and 83.8±4.8%, 87.4±2.7% and 84.4±1.3%, respectively. When further knocked down the expression of GLI1 by siRNA (mRNA decreased by 88.6±2.1%, protein decreased by 63.5±4.5%), DNMT1 and DNMT3a mRNA decreased by 80.9±2.3% and 78.6±3.8% and protein decreased by 64.8±2.8% and 67.5±5.6%, respectively. Over-expression of GLI1 by GLI1 gene transfection (mRNA increased by 655.5±85.9%, and protein increased by 272.3±14.4%.), DNMT1 and DNMT3a mRNA and protein increased by 293.0±14.8% and 578.3±58.5%, 143.5±17.4% and 214.0±18.9%, respectively. ChIP assays showed GLI1 protein bound to DNMT1 but not to DNMT3a. Results of nested MSP demonstrated GLI1 expression affected the DNA methylation level of APC but not hMLH1 in PC.
DNMT1 and DNMT3a are regulated by GLI1 in PC, and DNMT1 is its direct target gene.
PLoS ONE 01/2011; 6(11):e27684. · 4.09 Impact Factor
