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https://www.readbyqxmd.com/read/29771451/modulation-of-inflammatory-and-hormonal-parameters-in-response-to-testosterone-therapy-effects-on-the-ventral-prostate-of-adult-rats
#1
Leonardo O Mendes, Anthony C S Castilho, Cristiane F Pinho, Bianca F Gonçalvez, Eduardo M Razza, Luiz Gustavo A Chuffa, Janete A Anselmo-Franci, Wellerson R Scarano, Francisco E Martinez
Testosterone is often recommended in the treatment of several aging-related conditions. However, there are still questions about the consequences of this therapy in terms of hormonal and inflammatory parameters that are crucial for prostate homeostasis.Thus, we investigate if the testosterone therapy (TT) modulates the hormone receptors and inflammatory cytokines in the ventral prostate of adult rats. Wistar rats aging 150 days were divided into two experimental groups(n = 10/group): T: received subcutaneous injections of testosterone cypionate (5mg/kg body weight) diluted in corn oil every other day for 4 weeks; and C: received corn oil as vehicle...
May 17, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29695515/novel-role-of-prostate-apoptosis-response-4-tumor-suppressor-in-b-cell-chronic-lymphocytic-leukemia
#2
Mary K McKenna, Sunil K Noothi, Sara S Alhakeem, Karine Z Oben, Joseph T Greene, Rajeswaran Mani, Kathryn L Perry, James P Collard, Jacqueline R Rivas, Gerhard Hildebrandt, Roger Fleischman, Eric B Durbin, John C Byrd, Chi Wang, Natarajan Muthusamy, Vivek M Rangnekar, Subbarao Bondada
Prostate apoptosis response-4 (Par-4), a pro-apoptotic tumor suppressor protein, is down regulated in many cancers including renal cell carcinoma, glioblastoma, endometrial and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from the Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1 to S cell cycle transition...
April 25, 2018: Blood
https://www.readbyqxmd.com/read/29695020/significant-hypo-responsiveness-to-gpvi-and-clec-2-agonists-in-pre-term-and-full-term-neonatal-platelets-and-following-immune-thrombocytopenia
#3
Alexander T Hardy, Verónica Palma-Barqueros, Stephanie K Watson, Jean-Daniel Malcor, Johannes A Eble, Elizabeth E Gardiner, José E Blanco, Rafael Guijarro-Campillo, Juan L Delgado, María L Lozano, Raúl Teruel-Montoya, Vicente Vicente, Steve P Watson, José Rivera, Francisca Ferrer-Marín
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation...
April 25, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29672923/dual-role-of-par-4-in-abrogation-of-emt-and-switching-on-mesenchymal-to-epithelial-transition-met-in-metastatic-pancreatic-cancer-cells
#4
Archana Katoch, Sujit Suklabaidya, Souneek Chakraborty, Debasis Nayak, Reyaz Ur Rasool, Deepak Sharma, Debaraj Mukherjee, Mir Mohd Faheem, Anmol Kumar, Parduman Raj Sharma, Shantibhusan Senapati, Lekha Dinesh Kumar, Anindya Goswami
Epithelial-mesenchymal transition (EMT), a critical event that occurs during invasion and metastatic spread of cancer cells. Here, we conceive a dual mechanism of Par-4-mediated inhibition of EMT and induction of MET in metastatic pancreatic cancer cells. First, we demonstrate that 1,1'-β-D-glucopyranosyl-3,3'-bis(5-bromoindolyl)-octyl methane (NGD16), an N-glycosylated derivative of medicinally important phytochemical 3,3'-diindolylmethane (DIM) abrogates EMT by inducing pro-apoptotic protein Par-4. Induction of Par-4 (by NGD16 or ectopic overexpression) strongly impedes invasion with inhibition of major mesenchymal markers viz...
April 19, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29656006/par-4-dependent-p53-up-regulation-plays-a-critical-role-in-thymoquinone-induced-cellular-senescence-in-human-malignant-glioma-cells
#5
Karthikeyan Subburayan, Faisal Thayyullathil, Siraj Pallichankandy, Anees Rahman, Sehamuddin Galadari
Thymoquinone (TQ), the predominant bioactive constituent present in black cumin (Nigella sativa), exerts tumor suppressive activity against a wide variety of cancer cells. Cellular senescence, characterized by stable and long term loss of proliferative capacity, acts as a potent tumor suppressive mechanism. Here, we provide evidence for the first time that TQ suppresses growth of glioma cells by potentially inducing the expression of prostate apoptosis response-4 (Par-4) tumor suppressor protein. In turn, TQ-induced Par-4 expression triggers cellular senescence, as evidenced by increasing cellular size, β-galactosidase staining, G1 phase arrest, and increased expression of senescence markers such as p53, p21, Rb, and decreased expression of lamin B1, cyclin E and cyclin depended kinase-2 (CDK-2)...
April 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29439694/cardiometabolic-disorder-reduces-survival-prospects-more-than-suboptimal-body-mass-index-irrespective-of-age-or-gender-a-longitudinal-study-of-377-929-adults-in-taiwan
#6
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
https://www.readbyqxmd.com/read/29378352/atherothrombosis-and-thromboembolism-position-paper-from-the-second-maastricht-consensus-conference-on-thrombosis
#7
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
https://www.readbyqxmd.com/read/29330285/foxo-dependent-par-4-upregulation-prevents-long-term-survival-of-residual-cells-following-pi3k-akt-inhibition
#8
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 proapoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans...
April 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29317264/the-genetics-of-chronic-itch-gene-expression-in-the-skin-of-patients-with-atopic-dermatitis-and-psoriasis-with-severe-itch
#9
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 nonitchy, nonlesional skin biopsies from 25 patients with atopic dermatitis and 25 patients with psoriasis and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared with healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and nonitchy skin in atopic and psoriatic subjects...
January 6, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29278364/tnf-%C3%AE-and-ifn-%C3%AE-together-up-regulates-par-4-expression-and-induce-apoptosis-in-human-neuroblastomas
#10
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
https://www.readbyqxmd.com/read/29249426/par-4-the-paragon-of-protease-activated-receptors
#11
EDITORIAL
Tobias Geisler
No abstract text is available yet for this article.
February 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29249425/evidence-for-functional-par-4-thrombin-receptor-expression-in-cardiac-fibroblasts-and-its-regulation-by-high-glucose-par-4-in-cardiac-fibroblasts
#12
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
https://www.readbyqxmd.com/read/29115593/mir-17-3p-regulates-the-proliferation-and-survival-of-colon-cancer-cells-by-targeting-par4
#13
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
https://www.readbyqxmd.com/read/29105468/-effect-of-manual-acupuncture-electroacupuncture-and-moxibustion-on-intestinal-motility-and-expression-of-enteric-nervous-activity-related-proteins-in-functional-constipation-rats
#14
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
https://www.readbyqxmd.com/read/29089436/protease-mediated-suppression-of-drg-neuron-excitability-by-commensal-bacteria
#15
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
https://www.readbyqxmd.com/read/29044290/protease-activated-receptor-par-4-an-inducible-switch-between-thrombosis-and-vascular-inflammation
#16
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
https://www.readbyqxmd.com/read/28981200/soluble-fibrin-causes-an-acquired-platelet-glycoprotein-vi-signaling-defect-implications-for-coagulopathy
#17
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
https://www.readbyqxmd.com/read/28971310/recombinant-production-and-characterization-of-sac-the-core-domain-of-par-4-by-sumo-fusion-system
#18
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...
April 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28874459/protease-activated-receptor-2-activates-airway-apical-membrane-chloride-permeability-and-increases-ciliary-beating
#19
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...
January 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28759536/ranking-prediction-model-using-the-competition-record-of-ladies-professional-golf-association-players
#20
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
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