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Chih-Cheng Hsu, Mark L Wahlqvist, I-Chien Wu, Yu-Hung Chang, I-Shou Chang, Yi-Fen Tsai, Ting-Ting Liu, Chwen Keng Tsao, Chao A Hsiung
BACKGROUND: The effect of cardio-metabolic profile on the relationship of body mass index (BMI) with mortality is unclear. The aim of this study was to explore association between BMI and mortality at all ages, taking account of cardio-metabolic disorders. METHODS: We followed 377,929 individuals (≥ 20 years), who registered for health checkups in 1996-2007, until 2008 and found 9490 deaths. From multivariable Cox proportional hazards models we estimated mortality hazard ratios (HR) for those in high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and different BMIs categories (the underweight [< 18...
February 14, 2018: BMC Public Health
H M H Spronk, T Padro, J E Siland, J H Prochaska, J Winters, A C van der Wal, J J Posthuma, G Lowe, E d'Alessandro, P Wenzel, D M Coenen, P H Reitsma, W Ruf, R H van Gorp, R R Koenen, T Vajen, N A Alshaikh, A S Wolberg, F L Macrae, N Asquith, J Heemskerk, A Heinzmann, M Moorlag, N Mackman, P van der Meijden, J C M Meijers, M Heestermans, T Renné, S Dólleman, W Chayouâ, R A S Ariëns, C C Baaten, M Nagy, A Kuliopulos, J J Posma, P Harrison, M J Vries, H J G M Crijns, E A M P Dudink, H R Buller, Y M C Henskens, A Själander, S Zwaveling, O Erküner, J W Eikelboom, A Gulpen, F E C M Peeters, J Douxfils, R H Olie, T Baglin, A Leader, U Schotten, B Scaf, H M M van Beusekom, L O Mosnier, L van der Vorm, P Declerck, M Visser, D W J Dippel, V J Strijbis, K Pertiwi, A J Ten Cate-Hoek, H Ten Cate
Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1...
February 2018: Thrombosis and Haemostasis
Jeffrey S Damrauer, Stephanie N Phelps, Katie Amuchastegui, Ryan Lupo, Nathaniel W Mabe, Andrea Walens, Benjamin R Kroger, James V Alvarez
Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathways that regulate residual cancer cell survival may suggest opportunities for targeting these cells to prevent recurrence. Previously it was observed that the pro-apoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans...
January 12, 2018: Molecular Cancer Research: MCR
Leigh A Nattkemper, Hong Liang Tey, Rodrigo Valdes-Rodriguez, Helen Lee, Nicholas K Mollanazar, Christian Albornoz, Kristen M Sanders, Gil Yosipovitch
To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and non-itchy, non-lesional skin biopsies from 25 atopic dermatitis (AD) and 25 psoriasis patients and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared to healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and non-itchy skin in atopic and psoriatic subjects...
January 6, 2018: Journal of Investigative Dermatology
Ganesh V Shelke, Jayashree C Jagtap, Dae-Kyum Kim, Reecha D Shah, Gowry Das, Mruthyunjaya Shivayogi, Radha Pujari, Padma Shastry
The objective of this study was to examine the combined effect of Interferon-gamma (IFN-γ) and Tumor Necrosis factor-alpha (TNF-α) on cytotoxicity and expression of prostate apoptosis response-4 (Par-4) and Par-4 interacting proteins B-cell lymphoma (Bcl-2), nuclear factor kappa-light-chain-enhancer of activated B cells/p65 subunit (NF-κB/p65), Ak mouse strain thymoma (Akt) in human neuroblastoma (NB) cells. Materials and methods included human neuroblastoma cell lines-SK-N-MC, SK-N-SH, and SH-SY5Y, which were treated with IFN-γ and TNF-α individually, or in combination, and were assessed for viability by tetrazolium (MTT) assay...
December 26, 2017: Biomedicines
Tobias Geisler
No abstract text is available yet for this article.
February 1, 2018: International Journal of Cardiology
Sonja Kleeschulte, Johann Jerrentrup, Daniel Gorski, Joachim Schmitt, Anke C Fender
BACKGROUND: Thrombin promotes cardiac fibroblast proliferation and fibrosis via protease-activated receptor (PAR-1). PAR-4 is reportedly absent in cardiac fibroblasts. In smooth muscle cells, PAR-4 expression is also low but increases upon hyperglycemia and contributes to vascular remodelling in diabetic mice. We examined if PAR-4 is a glucose-responsive gene with remodelling-related functions in cardiac fibroblasts. METHODS AND RESULTS: Cardiac PAR-4 increased in mice with streptozotocin- or diabetogenic diet (DD)-induced diabetes...
February 1, 2018: International Journal of Cardiology
Debao Lu, Liang Tang, Yan Zhuang, Peng Zhao
Colorectal cancer (CRC) is a common malignancy worldwide. However, the pathogenesis by which CRC progression occurs remains to be elucidated. The present study investigated the role of miRNA (miR)‑17‑3P in the regulation of CRC cell survival. Firstly, miR‑17‑3P expression was aberrantly upregulated in human CRC tumor tissues compared with controls. Further results demonstrated that the proliferation capacity of human CRC SW480 and LoVo cells was significantly increased by an miR‑17‑3P specific mimic, and was inhibited by miR‑17‑3P silencing...
January 2018: Molecular Medicine Reports
Xin Zhang, Xuan-Ping Zhang, Yu-Zhu Du, Hai-Jiao Xing, Rui Jia, Li-Jia Pan, Jing Xu, Chun-Sheng Jia
OBJECTIVE: To compare the effect of manual acupuncture (MA), electroacupuncture (EA) and moxibustion interventions on intestinal motility and expression of enteric nervous activity related proteins calcitonin gene related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV 1) and proteinase activated receptor-4 (PAR-4) in colon tissue of rats with functional constipation (FC), so as to select a better intervention method for FC. METHODS: Sixty male SD rats were randomly divided into blank control (n=8), model (n=11), medication (n=8), MA (n=11), EA (n=11), and moxibustion (n=11) groups...
October 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
Jessica L Sessenwein, Corey C Baker, Sabindra Pradhananga, Megan E Maitland, Elaine O Petrof, Emma Allen-Vercoe, Curtis Noordhof, David E Reed, Stephen J Vanner, Alan E Lomax
Peripheral pain signaling reflects a balance of pronociceptive and antinociceptive influences; the contribution by the gastrointestinal microbiota to this balance has received little attention. Disorders, such as inflammatory bowel disease and irritable bowel syndrome, are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal gastrointestinal bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse DRG neurons...
November 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Anke C Fender, Bernhard H Rauch, Tobias Geisler, Karsten Schrör
Thrombin triggers activation of platelets through protease-activated receptor 1 (PAR-1) and PAR-4. Both receptors are widely expressed and exert multiple platelet-independent functions. PAR signalling contributes to healing responses after injury, by promoting cytokine activity and cellular growth and mobility. Uncontrolled PAR activation, however, can prevent timely resolution of inflammation, enhance thrombogenic endothelial function and drive adverse remodelling. The specific role of PAR-4 in thromboinflammatory vascular disease has been largely underestimated, given the relatively limited expression of PAR-4 in non-platelet cells under healthy conditions...
November 2017: Thrombosis and Haemostasis
M Y Lee, C C Verni, B A Herbig, S L Diamond
Essentials Collagen and thrombin when used simultaneously generate highly activated platelets. The effect of thrombin stimulation on subsequent glycoprotein VI (GPVI) function was observed. Soluble fibrin, but not protease activated receptor (PAR) activation, prevented GPVI activation. Circulating soluble fibrin in coagulopathic blood may cause an acquired GPVI signaling defect. SUMMARY: Background In coagulopathic blood, circulating thrombin may drive platelet dysfunction. Methods/Results Using calcium dye-loaded platelets, the effect of thrombin exposure and soluble fibrin generation on subsequent platelet GPVI function was investigated...
December 2017: Journal of Thrombosis and Haemostasis: JTH
Jian Zhang, Aiyou Sun, Yuguo Dong, Dongzhi Wei
Prostate apoptosis response-4 (Par-4), an anticancer protein that interacts with cell surface receptor GRP78, can selectively suppress proliferation and induce apoptosis of cancer cells. The core domain of Par-4 (aa 137-195), designated as SAC, is sufficient to inhibit tumor growth and metastasis without harming normal tissues and organs. Nevertheless, the anticancer effects of SAC have not been determined in ovarian cancer cells. Here, we developed a novel method for producing native SAC in Escherichia coli using a small ubiquitin-related modifier (SUMO) fusion system...
October 2, 2017: Applied Biochemistry and Biotechnology
Derek B McMahon, Alan D Workman, Michael A Kohanski, Ryan M Carey, Jenna R Freund, Benjamin M Hariri, Bei Chen, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Robert J Lee
Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl(-) current...
September 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jin Seok Chae, Jin Park, Wi-Young So
The purpose of this study was to suggest a ranking prediction model using the competition record of the Ladies Professional Golf Association (LPGA) players. The top 100 players on the tour money list from the 2013-2016 US Open were analyzed in this model. Stepwise regression analysis was conducted to examine the effect of performance and independent variables (i.e., driving accuracy, green in regulation, putts per round, driving distance, percentage of sand saves, par-3 average, par-4 average, par-5 average, birdies average, and eagle average) on dependent variables (i...
July 28, 2017: Journal of Strength and Conditioning Research
Jun Wang, Yunjie Li, Fangfang Ma, Huifeng Zhou, Rong Ding, Binbin Lu, Li Zou, Junxia Li, Rugang Lu
Wilms' tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms' tumor. Wilms' tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic agents targeting this process, termed selective inhibitors of nuclear export (SINE), have demonstrated antitumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1), which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma, adenomatous polyposis coli, p53, p73, p21, p27, forkhead box O, signal transducer and activator of transcription 3, inhibitor of κB, topoisomerase II, and protease activated receptor 4-is the principal focus of development of SINE...
September 2017: Journal of Thoracic Oncology
Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S J Elenitoba-Johnson, Vivek M Rangnekar
Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth...
August 1, 2017: Cancer Research
Laura Roesler Nery, Natalia Eltz Silva, Raphaela Fonseca, Monica Ryff Moreira Vianna
Presenilins are transmembrane proteases required for the proteolytic cleavage of Notch and also act as the catalytic core of the γ-secretase complex, which is responsible for the final cleavage of the amyloid precursor protein into Amyloid-β (Aβ) peptides of varying lengths. Presenilin-1 gene (psen1) mutations are the main cause of early-onset autosomal-dominant Familial Alzheimer Disease. Elucidating the roles of Presenilin-1 and other hallmark proteins involved in Alzheimer's disease is crucial for understanding the disease etiology and underlying molecular mechanisms...
October 2017: Neurochemical Research
Udaya K Tiruttani Subhramanyam, Jan Kubicek, Ulf B Eidhoff, Joerg Labahn
Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization...
September 2017: Cell Death and Differentiation
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