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| 2. |
- Ding, Jun-Li, et al.
(författare)
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Attenuation of Acute Pancreatitis by Peroxisome Proliferator-Activated Receptor-α in Rats: The Effect on Toll-Like Receptor Signaling Pathways
- 2013
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Ingår i: Pancreas. - : Lippincott, Williams and Wilkins. - 0885-3177 .- 1536-4828. ; 42:1, s. 114-122
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The peroxisome proliferator-activated receptor-α (PPAR-α) has attracted considerable attention for its anti-inflammatory properties; however, Toll-like receptor (TLR) pathways have an essential proinflammatory role in acute pancreatitis (AP). This study aimed to evaluate the attenuation of inflammation by PPAR-α and to investigate the interaction between PPAR-α and TLR pathways in AP.Methods: Acute pancreatitis was induced in rats by administration of cerulein. The PPAR-α agonist WY14643 and/or antagonist MK886 was administered. The severity of AP was determined by measuring serum amylase, lipase, Ca2+, pathological changes, myeloperoxidase activity, serum levels of interleukin (IL)-6, and intercellular adhesion molecule-1 (ICAM-1). The TLR2 and TLR4 messenger RNA (mRNA) and proteins were determined by real-time reverse transcriptase polymerase chain reaction and Western blotting, respectively. The mRNA expressions of target molecules of TLR pathways, including IL-6, IL-10, ICAM-1, and tumor necrosis factor α were also measured.Results: Treatment with WY14643 significantly decreased amylase, lipase, myeloperoxidase activity, pathological scores, IL-6, and ICAM-1 levels. The TLR2 and TLR4 mRNA and proteins were markedly decreased after treatment with WY14643, along with IL-6, ICAM-1, and tumor necrosis factor α mRNA levels. However, these effects were completely reversed by the coadministration of MK886.Conclusions: Activation of PPAR-α played a protective role in AP, partially mediated by modulation of TLR pathways.
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| 3. |
- Liu, Guang-Hui, et al.
(författare)
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Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer
- 2013
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Ingår i: Tumor Biology. - : Karger / Springer Verlag (Germany). - 1010-4283 .- 1423-0380. ; 34:4, s. 2175-2181
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies from our laboratory identified a number of miRNAs that were aberrantly expressed in colorectal cancer (CRC) tissue. However, their diagnostic and prognostic value in serum has not been fully evaluated. In the present study, we measured the levels of five miRNAs (miR-21, miR-31, miR-92a, miR-18a, and miR-106a) in serum samples from 200 CRC patients, 50 advanced adenoma patients, and 80 healthy controls by real-time quantitative polymerase chain reaction (RT-PCR). In our study, the levels of miR-21 and miR-92a in patients with CRC and advanced adenoma were significantly higher than those in healthy controls (all P < 0.05). MiR-21 yielded an area under the receiver-operating characteristics (ROC) curve (AUC) of 0.802 and miR-92a yielded an AUC of 0.786 in discriminating CRCs from the controls. Additionally, miR-21 and miR-92a yielded an AUC of 0.709 and 0.701, respectively, in discriminating advanced adenomas from the controls. Combined ROC analyses using both miRNAs, revealed an elevated AUC of 0.847 in discriminating CRCs, and an AUC of 0.722 in discriminating advanced adenomas from the controls. In the multivariate Cox proportional hazards analysis, high miR-92a expression in CRC was independently associated with poor survival (P = 0.03; hazard ratio 4.36; 95 % confidence interval = 1.64–11.57). No significant difference was observed in the levels of miR-18a, miR-31, and miR-106a among CRC, advanced adenoma, and control samples. In summary, our data indicate that miR-21 and miR-92a serum levels have potential value for early detection of CRC. Furthermore, miR-92a has prognostic value in CRC patients.
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| 4. |
- Liu, Yong, et al.
(författare)
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Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury
- 2016
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : AMER PHYSIOLOGICAL SOC. - 0193-1857 .- 1522-1547. ; 310:5, s. G303-G309
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Tidskriftsartikel (refereegranskat)abstract
- Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
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| 5. |
- Zhou, Jin, et al.
(författare)
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The prognostic significance of peroxisome proliferator-activated receptor beta expression in the vascular endothelial cells of colorectal cancer
- 2014
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Ingår i: Journal of gastroenterology. - : Springer Verlag (Germany). - 0944-1174 .- 1435-5922. ; 49:3, s. 436-445
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Tidskriftsartikel (refereegranskat)abstract
- Currently, little is known regarding the role of peroxisome proliferator-activated receptor-beta (PPAR beta) in the vascular endothelial cells (VECs) of colorectal cancers (CRCs). The aim of this study was to investigate the relationship of PPAR beta expression in the VECs of CRCs in terms of the prognosis and clinicopathological features of CRC patients. The expression and localization of PPAR beta in the primary cancers and the matched normal mucosal samples of 141 Swedish CRC patients were analyzed in terms of its correlation with clinicopathological features and the expression of angiogenesis-related genes. This study also included 92 Chinese CRC patients. PPAR beta was predominantly localized in the cytoplasm and was significantly downregulated in the VECs of CRC compared to that of the normal mucosa. The low expression levels of PPAR beta in the VECs of CRC were statistically correlated with enhanced differentiation, early staging and favorable overall survival and were associated with the increased expression of VEGF and D2-40. The patients exhibiting elevated expression of PPAR beta in CRC cells but reduced expression in VECs exhibited more favorable survival compared with the other patients, whereas the patients with reduced expression of PPAR beta in CRC cells but increased expression in VECs exhibited less favorable prognosis. PPAR beta might play a tumor suppressor role in CRC cells in contrast to a tumor promoter role in the VECs of CRCs.
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| 6. |
- Zhou, Xiang-Yu, et al.
(författare)
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TRAF6 as the Key Adaptor of TLR4 Signaling Pathway Is Involved in Acute Pancreatitis
- 2010
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Ingår i: PANCREAS. - 0885-3177. ; 39:3, s. 359-366
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study the potential role of tumor necrosis factor receptor-associated factor 6 (TRAF6) as the key adaptor of the toll-like receptor 4 (TLR4) signaling pathway in acute pancreatitis (AP) in mice. Methods: Acute pancreatitis was induced by 7 intraperitoneal injections of cerulein in TLR4-deficient (TLR4-Def) and TLR4 wild-type (TLR4-WT) mice. Inflammatory severity was scored and evaluated based on pathological study. TRAF6 expression was determined by reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry. Results: Acute pancreatitis was successfully induced in both mice strains, but the inflammatory progression was different. In TLR4-Def mice, pancreatic inflammation was blunt and mild first, then became increasingly intensive and peaked at the later stage, whereas in the TLR4-WT mice, the response was fast initiated and peaked at the early stage of AP, then alleviated gradually. TRAF6 expression in TLR4-Def mice was significantly higher than that in the TLR4-WT mice. Immunohistochemistry located TRAF6 expressed mainly in the pancreatic acinar cells. Conclusions: The TLR4-TRAF6 signaling pathway is critically involved in AP. Other signaling pathways beyond TLR4 may participate in the pancreatic inflammatory process via TRAF6. As a convergence point of the TLR4-dependent and the TLR4-independent signaling pathways, TRAF6 plays an important role in AP.
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| 7. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 9. |
- Chen, Ke-Ling, et al.
(författare)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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