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Green fluorescent protein selectively induces HSP70-mediated up-regulation of COX-2 expression in endothelial cells 下载免费PDF全文
Zhang F Hackett NR Lam G Cheng J Pergolizzi R Luo L Shmelkov SV Edelberg J Crystal RG Rafii S 《Blood》2003,102(6):2115-2121
Reporter genes, including green fluorescent protein (GFP), have been used to monitor the expression of transgenes introduced into vascular cells by gene transfer vectors. Here, we demonstrate that GFP by itself can selectively induce expression of certain genes in endothelial cells. Elevation of the cytoplasmic concentration of GFP in endothelial cells, specifically, resulted in a robust upregulation of heat shock protein 70 (HSP70). GFP induced both mRNA and protein expression of HSP70 in a dose-dependent manner. GFP-mediated up-regulation of HSP70 resulted in induction of cyclooxygenase-2 (COX-2) followed by prostaglandin E2 (PGE2) production. GFP-mediated up-regulation of HSP70 is independent of mitogen-activated protein kinase and phosphatidylinositol-3-kinase signaling cascades because inhibition of these pathways had no effect on HSP70 increases. Adenoviral delivery of GFP into murine vasculature significantly enhanced blood flow, suggesting that sufficient PGE2 is produced to induce vasodilation. Identification of the molecular partners that interact with GFP will increase our understanding of the vascular-specific factors that regulate stress angiogenesis and hemostasis. 相似文献
104.
The articles in this supplement were developed from a recent pan-European conference entitled 'HIV in Europe 2007: Working together for optimal testing and earlier care', which took place on 26–27 November in Brussels, Belgium. The conference, organized by a multidisciplinary group of experts representing advocacy, clinical and policy areas of the HIV field, was convened in an effort to gain a common understanding on the role of HIV testing and counselling in optimizing diagnosis and the need for earlier care. Key topics discussed at the conference and described in the following articles include: current barriers to HIV testing across Europe, trends in the epidemiology of HIV in the region, problems associated with undiagnosed infection and the psychosocial barriers impacting on testing. The supplement also provides a summary of the World Health Organization's recommendations for HIV testing in Europe and an outline of an indicator disease-guided approach to HIV testing proposed by a committee of experts from the European AIDS Clinical Society (EACS). We hope that consideration of the issues discussed in this supplement will help to shift the HIV field closer towards our ultimate goal: provision of optimal HIV testing and earlier care across the whole of the European region. 相似文献
105.
Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response 下载免费PDF全文
106.
Joseph V. Pergolizzi MD Jr Robert Taylor PhD Jr Robert B. Raffa PhD 《Pain practice》2015,15(4):378-388
Despite recent advances in the knowledge of pain mechanisms and pain management, postoperative pain continues to be a problem. Inadequately managed postsurgical pain has both clinical and economic consequences such as longer recovery times, delayed ambulation, higher incidence of complications, increased length of hospital stay, and potential to develop into chronic pain. Generally, opioids are the mainstay option for pain management in patients with moderate‐to‐severe postsurgical pain; however, opioids have significant side effects and have abuse potential. To improve patient and economic outcomes after surgery, postoperative pain guidelines have suggested incorporating a multi‐modal/multi‐mechanistic approach to pain treatment. A multi‐modal approach is the simultaneous use of a combination of two or more (usually opioid and non‐opioid) analgesics that provide two different mechanisms of actions. Utilizing a multi‐modal approach may result in a greater reduction in pain vs. single therapies in addition to minimizing opioid use, thus reducing opioid related side effects. However, not all approaches may be effective for all types of patients and not all analgesics may be a viable option for outpatient settings, ambulatory surgery, or the fast‐track surgical procedures. In this report, we present a review of the literature with a focus on intranasal ketorolac in order to provide a timely update regarding past, present, and future multi‐modal treatment options for postoperative pain. 相似文献
107.
Oral Diseases (2010) 16 , 119–128 Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck area. They are classically divided into two subgroups, Hodgkin’s lymphomas (HLs) and non‐Hodgkin’s lymphomas (NHLs). We describe the clinical characteristics of head and neck lymphomas and the methods to establish the diagnosis. The World Health Organization classification of lymphoid tissues describes more than 50 different histological types, and we analyse the most common staging system for lymphomas, the Ann Arbor staging system. Finally, the different therapeutic approaches are discussed. 相似文献
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C Hernández E Santamatilde KJ McCreath AM Cervera I Díez D Ortiz-Masiá N Martínez S Calatayud JV Esplugues MD Barrachina 《British journal of pharmacology》2009,156(2):262-272
Background and purpose:
Mucosal microcirculation is compromised during gastric damage induced by non-steroidal anti-inflammatory drugs, such as aspirin. Consequently, oxygen supply to epithelial cells is decreased. The trefoil factor (TFF) peptides are involved in mechanisms of defence and repair in the gastrointestinal tract but their regulation at sites of gastric injury is unknown.Experimental approach:
Hypoxia and expression of TFF genes and peptides were measured in the damaged stomach of aspirin-treated rats. In a human gastric cell line (AGS cells), the effects of hypoxia and of hypoxia inducible factor (HIF)-1 (through transient transfection of HIF-1α siRNA or over-expression of HIF-1α) on TFF gene expression were evaluated.Key results:
Hypoxyprobe immunostaining, up-regulation of TFF2 (1.9-fold) and TFF3 (1.8-fold) and a non-significant increase of TFF1 (1.5-fold) mRNA were observed in the damaged stomach of aspirin-treated rats, compared with control animals. Hypoxia (3% O2, 16 h) induced mRNA for TFF1 (5.8-fold), TTF2 (9.1-fold) and TFF3 (9.3-fold) in AGS cells, an effect mediated by HIF-1, as transient transfection of HIF-1α siRNA reduced the effects of hypoxia. Over-expression of HIF-1α by transfection in non-hypoxic epithelial cells produced a similar pattern of TFF induction to that observed with hypoxia and transactivated a TFF1 reporter construct.Conclusions and implications:
Hypoxia inducible factor-1 mediated the induction of TFF gene expression by hypoxia in gastric epithelial cells. Low oxygen levels and up-regulation of TFF gene expression in the damaged stomach of aspirin-treated rats suggest that hypoxia induced expression of TFF genes at sites of gastric injury. 相似文献110.
N Apostolova LJ Gomez-Sucerquia A Moran A Alvarez A Blas-Garcia JV Esplugues 《British journal of pharmacology》2010,160(8):2069-2084