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https://www.readbyqxmd.com/read/28427942/inhibitory-effects-of-ethyl-pyruvate-on-platelet-aggregation-and-phosphatidylserine-exposure
#1
Wenjin Li, Xinyu Yang, Minyuan Peng, Can Li, Guangfu Mu, Fangping Chen
Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28427224/ponatinib-promotes-a-g1-cell-cycle-arrest-of-merlin-nf2-deficient-human-schwann-cells
#2
Alejandra M Petrilli, Jeanine Garcia, Marga Bott, Stephani Klingeman Plati, Christine T Dinh, Olena R Bracho, Denise Yan, Bing Zou, Rahul Mittal, Fred F Telischi, Xue-Zhong Liu, Long-Sheng Chang, D Bradley Welling, Alicja J Copik, Cristina Fernández-Valle
Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC)...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423550/quantitative-proteomic-analysis-of-gastric-cancer-tissue-reveals-novel-proteins-in-platelet-derived-growth-factor-b-signaling-pathway
#3
Fang Liu, Yuan Zhang, Tingting Men, Xingyue Jiang, Chunhua Yang, He Li, Xiaodan Wei, Dong Yan, Gangming Feng, Jianke Yang, Jonas Bergquist, Bin Wang, Wenguo Jiang, Jia Mi, Geng Tian
Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415580/the-n-terminal-polypeptide-derived-from-viral-macrophage-inflammatory-protein-ii-reverses-breast-cancer-epithelial-tomesenchymal-transition-via-a-pdgfra-dependent-mechanism
#4
Qing-Ling Yang, Ling-Yu Zhang, Hai-Feng Wang, Yu Li, Yue-Yue Wang, Tian-Tian Chen, Meng-Fen Dai, Hai-Hua Wu, Su-Lian Chen, Wen-Rui Wang, Qiong Wu, Chang-Jie Chen, Cong-Zhao Zhou
NT21MP, a 21-residue peptide derived from the viral macrophage inflammatory protein II, competed effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in breast cancer. Its role in tumor epithelial-to-mesenchymal transition (EMT) regulation remains unknown. In this study, we evaluated the reversal of EMT upon NT21MP treatment and examined its role in the inhibition of EMT in breast cancer. The parental cells of breast cancer (SKBR-3 and MCF-7) and paclitaxel-resistant (SKBR-3 PR and MCF-7 PR) cells were studied in vitro and in combined immunodeficient mice...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411253/a-new-path-to-platelet-production-through-matrix-sensing
#5
Vittorio Abbonante, Christian Andrea Di Buduo, Cristian Gruppi, Carmelo De Maria, Elise Spedden, Aurora De Acutis, Cristian Staii, Mario Raspanti, Giovanni Vozzi, David Kaplan, Francesco Moccia, Katya Ravid, Alessandra Balduini
Megakaryocytes in the bone marrow are immersed in a network of extracellular matrix (ECM) components that regulate platelet release into the circulation. Combining biological and bioengineering approaches, we found that the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechano-sensitive ion channel, is induced upon megakaryocyte adhesion on softer matrices. This response promoted platelet production by triggering a cascade of events that lead to calcium influx, β1 integrin activation and internalization, and Akt phosphorylation, responses not found on stiffer matrices...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#6
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28393245/knockdown-of-fstl1-inhibits-pdgf%C3%A2-bb%C3%A2-induced-human-airway-smooth-muscle-cell-proliferation-and-migration
#7
Yuelin Deng, Yao Zhang, Huajie Wu, Zhaoling Shi, Xin Sun
Abnormal proliferation and migration of airway smooth muscle (ASM) cells serve roles in airway remodeling, and contribute to airway hyper‑responsiveness. Follistatin‑like protein 1 (FSTL1) is a secreted glycoprotein that belongs to the follistatin family of proteins. It was reported that in the lungs of patients suffering from severe asthma, FSTL1 is highly expressed by macrophages. However, the role of FSTL1 in ASM cell proliferation and migration remains unknown. The present study aimed to investigate the role of FSTL1 in cell proliferation and migration mediated by platelet‑derived growth factor subunit B (PDGF‑BB) in human ASM cells...
April 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28388313/arachidonic-acid-and-docosahexanoic-acid-enhance-platelet-formation-from-human-apheresis-derived-cd34-cells
#8
Ankita Dhenge, Kedar Limbkar, Sameer Melinkeri, Vaijayanti Prakash Kale, Lalita Limaye
An Aberration in megakaryopoiesis and thrombopoiesis, 2 important processes that maintain hemostasis, leads to thrombocytopenia. Though platelet transfusions are used to treat this condition, blood banks frequently face a shortage of platelets. Therefore, methods to generate platelets on a large scale are strongly desirable. However, to generate megakaryocytes (MKs) and platelets (PLTs) in numbers sufficient for clinical application, it is essential to understand the mechanism of platelet production and explore efficient strategies accordingly...
April 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#9
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28294559/the-platelet-activating-receptor-c-type-lectin-receptor-2-plays-an-essential-role-in-liver-regeneration-after-partial-hepatectomy-in-mice
#10
H Kono, H Fujii, K Suzuki-Inoue, O Inoue, S Furuya, K Hirayama, Y Akazawa, Y Nakata, C Sun, N Tsukiji, T Shirai, Y Ozaki
Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx. SUMMARY: Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice...
March 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28268217/a-phenanthrene-derivative-5-7-dimethoxy-1-4-phenanthrenequinone-inhibits-cell-adhesion-molecule-expression-and-migration-in-vascular-endothelial-and-smooth-muscle-cells
#11
Huey-Ming Lo, Tsong-Long Hwang, Wen-Bin Wu
The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs...
2017: Pharmacology
https://www.readbyqxmd.com/read/28266802/polydatin-inhibits-cell-proliferation-and-induces-apoptosis-in-laryngeal-cancer-and-hela-cells-via-suppression-of-the-pdgf-akt-signaling-pathway
#12
Haixia Li, Baoyuan Shi, Yanyun Li, Fengfang Yin
Polydatin (PD), a stilbene compound extracted from Polygonum cuspidatum, is suggested to possess anti-cancer activities, including inhibition of cell proliferation, cell cycle arrest, and induction of apoptosis. The platelet-derived growth factor (PDGF)/AKT signaling pathway plays complex roles in tumor suppression. However, the effect of PD on the PDGF/AKT signaling pathway in laryngeal cancer and HeLa cells has not been explored. MTT assay and flow cytometry showed that PD inhibited cell proliferation and induced apoptosis in Hep-2 and AMC-HN-8 cells...
March 7, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28260800/a-novel-stat3-inhibitor-negatively-modulates-platelet-activation-and-aggregation
#13
Zhuan Xu, Yu-Jia Xu, Ya-Nan Hao, Li-Jie Ren, Zu-Bin Zhang, Xin Xu, Bi-Yin Cao, Ke-Sheng Dai, Li Zhu, Qi Fang, Yan Kong, Xin-Liang Mao
The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively...
March 6, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28255363/exosomes-derived-from-human-platelet-rich-plasma-prevent-apoptosis-induced-by-glucocorticoid-associated-endoplasmic-reticulum-stress-in-rat-osteonecrosis-of-the-femoral-head-via-the-akt-bad-bcl-2-signal-pathway
#14
Shi-Cong Tao, Ting Yuan, Bi-Yu Rui, Zhen-Zhong Zhu, Shang-Chun Guo, Chang-Qing Zhang
An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material...
2017: Theranostics
https://www.readbyqxmd.com/read/28245285/the-platelet-derived-growth-factor-receptor-stat3-signaling-pathway-regulates-the-phenotypic-transition-of-corpus-cavernosum-smooth-muscle-in-rats
#15
Jun-Feng Yan, Wen-Jie Huang, Jian-Feng Zhao, Hui-Ying Fu, Gao-Yue Zhang, Xiao-Jun Huang, Bo-Dong Lv
Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28242694/receptor-interacting-protein-kinase-3-promotes-platelet-activation-and-thrombosis
#16
Yiwen Zhang, Jian Zhang, Rong Yan, Jingluan Tian, Yang Zhang, Jie Zhang, Mengxing Chen, Qingya Cui, Lili Zhao, Renping Hu, Miao Jiang, Zhenyu Li, Changgeng Ruan, Sudan He, Kesheng Dai
Previous studies have shown that receptor-interacting protein kinase 3 (RIP3) is involved in many important biological processes, including necroptosis, apoptosis, and inflammation. Here we show that RIP3 plays a critical role in regulating platelet functions and in vivo thrombosis and hemostasis. Tail bleeding times were significantly longer in RIP3-knockout (RIP3(-/-)) mice compared with their wild-type (WT) littermates. In an in vivo model of arteriole thrombosis, mice lacking RIP3 exhibited prolonged occlusion times...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28237515/adiporon-an-adiponectin-receptor-agonist-attenuates-pdgf-induced-vsmc-proliferation-through-inhibition-of-mtor-signaling-independent-of-ampk-implications-toward-suppression-of-neointimal-hyperplasia
#17
Arwa Fairaq, Noha M Shawky, Islam Osman, Prahalathan Pichavaram, Lakshman Segar
Hypoadiponectinemia is associated with an increased risk of coronary artery disease. Although adiponectin replenishment mitigates neointimal hyperplasia and atherosclerosis in mouse models, adiponectin therapy has been hampered in a clinical setting due to its large molecular size. Recent studies demonstrate that AdipoRon (a small-molecule adiponectin receptor agonist) improves glycemic control in type 2 diabetic mice and attenuates postischemic cardiac injury in adiponectin-deficient mice, in part, through activation of AMP-activated protein kinase (AMPK)...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28220122/nf-%C3%AE%C2%BAb-links-tlr2-and-par1-to-soluble-immunomodulator-factor-secretion-in-human-platelets
#18
Pauline Damien, Fabrice Cognasse, Bernard Payrastre, Sherry L Spinelli, Neil Blumberg, Charles-Antoine Arthaud, Marie-Ange Eyraud, Richard P Phipps, Archibald McNicol, Bruno Pozzetto, Olivier Garraud, Hind Hamzeh-Cognasse
The primary toll-like receptor (TLR)-mediated immune cell response pathway common for all TLRs is MyD88-dependent activation of NF-κB, a seminal transcription factor for many chemokines and cytokines. Remarkably, anucleate platelets express the NF-κB machinery, whose role in platelets remains poorly understood. Here, we investigated the contribution of NF-κB in the release of cytokines and serotonin by human platelets, following selective stimulation of TLR2 and protease activated receptor 1 (PAR1), a classical and non-classical pattern-recognition receptor, respectively, able to participate to the innate immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28212891/sulforaphane-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cell-proliferation-by-targeting-mtor-p70s6kinase-signaling-independent-of-nrf2-activation
#19
Noha M Shawky, Lakshman Segar
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28194217/schisandra-chinensis-and-morus-alba-synergistically-inhibit-in-vivo-thrombus-formation-and-platelet-aggregation-by-impairing-the-glycoprotein-vi-pathway
#20
Dong-Seon Kim, Muhammad Irfan, Yoon-Young Sung, Seung Hyung Kim, Sun Haeng Park, Young Hyun Choi, Man Hee Rhee, Ho Kyoung Kim
Morus alba L. (MAL) extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC), has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and [Ca(2+)] i release assays were carried out...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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