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https://www.readbyqxmd.com/read/28634089/wedelolactone-a-plant-coumarin-prevents-vascular-smooth-muscle-cell-proliferation-and-injury-induced-neointimal-hyperplasia-through-akt-and-ampk-signaling
#1
Lu Peng, Xuefeng Huang, Xin Jin, Zuo Jing, Lichao Yang, Yu Zhou, Jie Ren, Yun Zhao
Wedelolactone (WDL) is a natural compound derived from Chinese herbal medicine Eclipta prostrate L, and has been reported to exhibit various effects potentially beneficial for human health. However, the possible preventive effects of WDL toward vascular remodeling and mechanisms involved have not been investigated to date. In this study, we investigated the effects of WDL on proliferation induced by platelet-derived growth factor (PDGF) in primary rat aortic smooth muscle cells (VSMCs) and on neointimal hyperplasia resulted from balloon injury in rats...
June 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28629815/resveratrol-suppresses-pulmonary-tumor-metastasis-by-inhibiting-platelet-mediated-angiogenic-responses
#2
Liwei He, Fangtian Fan, Xianbang Hou, Cuixiang Gao, Li Meng, Shu Meng, Shiwen Huang, Hongyan Wu
BACKGROUND: To explore the impact of Resveratrol (RSV) on the angiogenic potential of activated platelets and to elucidate the underlying mechanism. METHODS: Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay. Capillary tube formation assay was used to examine the impact of RSV on the angiogenic potential of activated platelets. The levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) in the supernatant were evaluated using corresponding enzyme-linked immunosorbent assay kits...
May 10, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28603902/extracellular-signal-regulated-kinase-5-associates-with-casein-kinase-ii-to-regulate-gpib-ix-mediated-platelet-activation-via-the-pten-pi3k-akt-pathway
#3
Z Cheng, W Gao, X Fan, X Chen, H Mei, J Liu, X Luo, Y Hu
BACKGROUND: The platelet glycoprotein (GP) Ib-IX complex plays essential roles in thrombosis and hemostasis. The mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 have been shown to be important in the GPIb-IX-mediated signaling leading to integrin activation. However, the roles of the MAPK extracellular signal-regulated kinase 5 (ERK5) in GPIb-IX-mediated platelet activation are unknown. OBJECTIVE: To reveal the function and mechanisms of ERK5 in GPIb-IX-mediated platelet activation...
June 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28577568/pirfenidone-inhibits-myofibroblast-differentiation-and-lung-fibrosis-development-during-insufficient-mitophagy
#4
Yusuke Kurita, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Kazuya Tsubouchi, Nahoko Sato, Masahiro Yoshida, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28576849/proteome-wide-identification-of-glycosylation-dependent-interactors-of-galectin-1-and-galectin-3-on-mesenchymal-retinal-pigment-epithelial-cells
#5
Jara Obermann, Claudia S Priglinger, Juliane Merl-Pham, Arie Geerlof, Sigfried Priglinger, Magdalena Götz, Stefanie M Hauck
Identification of interactors is a major goal in cell biology. Not only protein-protein but also protein-carbohydrate interactions are of high relevance for signal transduction in biological systems. Here we aim to identify novel interacting binding partners for the β-galactoside-binding proteins Galectin-1 (Gal-1) and Galectin-3 (Gal-3) relevant in the context of the eye disease proliferative vitreoretinopathy (PVR). PVR is one of the most common failures after retinal detachment surgeries and is characterized by the migration, adhesion and epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE) and the subsequent formation of sub- and epiretinal fibrocellular membranes...
June 2, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28511645/therapeutic-potential-of-tas-115-via-c-met-and-pdgfr%C3%AE-signal-inhibition-for-synovial-sarcoma
#6
Shutaro Yamada, Yoshinori Imura, Takaaki Nakai, Sho Nakai, Naohiro Yasuda, Keiko Kaneko, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Akira Myoui, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
BACKGROUND: The prognosis of synovial sarcoma (SS), an aggressive soft tissue sarcoma, remains poor. We previously reported that c-MET or platelet-derived growth factor receptor α (PDGFRα) signalling pathway is related to SS progression based upon the findings of phospho-receptor tyrosine kinase (RTK) arrays. TAS-115 is a novel c-MET/ vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitor that has been shown to inhibit multiple RTKs. Here we aimed to investigate the therapeutic potential of TAS-115 against SS...
May 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#7
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28497199/arachidonic-acid-induces-are-nrf2-dependent-heme-oxygenase-1-transcription-in-rat-brain-astrocytes
#8
Chih-Chung Lin, Chien-Chung Yang, Yu-Wen Chen, Li-Der Hsiao, Chuen-Mao Yang
Arachidonic acid (AA) is a major product of phospholipid hydrolysis catalyzed by phospholipase A2 during neurodegenerative diseases. AA exerts as a second messenger to regulate various signaling components which may be involved in different pathophysiological processes. Astrocytes are the main types of CNS resident cells which maintain and support the physiological function of brain. AA has been shown to induce ROS generation through activation of NADPH oxidases (Noxs) which may play a key role in the expression of heme oxygenase-1 (HO-1)...
May 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28492699/lipopolysaccharide-as-trigger-of-platelet-aggregation-via-eicosanoid-over-production
#9
Cristina Nocella, Roberto Carnevale, Simona Bartimoccia, Marta Novo, Roberto Cangemi, Daniele Pastori, Camilla Calvieri, Pasquale Pignatelli, Francesco Violi
The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15-100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H2O2 production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A2 and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp)...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28487975/decreased-phosphorylation-of-pdgfr-%C3%AE-impairs-the-angiogenic-potential-of-expanded-endothelial-progenitor-cells-via-the-inhibition-of-pi3k-akt-signaling
#10
Haiyuan Lu, Hua Mei, Fan Wang, Qian Zhao, Siqi Wang, Lvjun Liu, Lamei Cheng
Human umbilical cord blood-derived endothelial progenitor cells (EPCs) have been proven to contribute to post-natal angiogenesis, and have been applied in various models of ischemia. However, to date, to the best of our knowledge, there is no available data on the angiogenic properties of EPCs during the process of in vitro expansion. In this study, we expanded EPCs to obtain cells at different passages, and analyzed their cellular properties and angiogenic ability. In the process of expansion, no changes were observed in cell cobblestone-like morphology, apoptotic rate and telomere length...
June 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28486691/combined-kinase-inhibitors-of-mek1-2-and-either-pi3k-or-pdgfr-are-efficacious-in-intracranial-triple-negative-breast-cancer
#11
Amanda E D Van Swearingen, Maria J Sambade, Marni B Siegel, Shivani Sud, Robert S McNeill, Samantha M Bevill, Xin Chen, Ryan E Bash, Louisa Mounsey, Brian T Golitz, Charlene Santos, Allison Deal, Joel S Parker, Naim Rashid, C Ryan Miller, Gary L Johnson, Carey K Anders
Background: Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases...
May 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28457985/validation-of-aspirin-response-related-transcripts-in-patients-with-coronary-artery-disease-and-preliminary-investigation-on-cmtm5-function
#12
J W Zhang, T F Liu, X H Chen, W Y Liang, X R Feng, L Wang, Sidney W Fu, Timothy A McCaffrey, M L Liu
Aspirin is widely used in the prevention of cardiovascular diseases, but the antiplatelet responses vary from one patient to another. To validate aspirin response related transcripts and illustrate their roles in predicting cardiovascular events, we have quantified the relative expression of 14 transcripts previously identified as related to high on-aspirin platelet reactivity (HAPR) in 223 patients with coronary artery disease (CAD) on regular aspirin treatment. All patients were followed up regularly for cardiovascular events (CVE)...
August 15, 2017: Gene
https://www.readbyqxmd.com/read/28448438/antiplatelet-activity-of-a-newly-synthesized-novel-ruthenium-ii-a-potential-role-for-akt-jnk-signaling
#13
Themmila Khamrang, Kuo-Chen Hung, Chih-Hsuan Hsia, Cheng-Ying Hsieh, Marappan Velusamy, Thanasekaran Jayakumar, Joen-Rong Sheu
In oncotherapy, ruthenium complexes are considered as potential alternatives for platinum compounds, and have been proved as promising anticancer drugs with high efficacy and lesser side effects. Platelet activation plays a major role in cancer metastasis and progression. Hence, this study explored the effect of a newly synthesized ruthenium complex, [Ru(η⁶-cymene)(L)Cl]BF₄(TQ5), where L = 4-phenyl-2-pyridin-2-yl-quinazoline), on human platelet activation. TQ5 (3-5 µM) inhibited concentration-dependent collagen-induced platelet aggregation in washed human platelets...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28427942/inhibitory-effects-of-ethyl-pyruvate-on-platelet-aggregation-and-phosphatidylserine-exposure
#14
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
#15
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)...
May 9, 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
#16
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-to-mesenchymal-transition-via-a-pdgfr%C3%AE-dependent-mechanism
#17
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...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411253/a-new-path-to-platelet-production-through-matrix-sensing
#18
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
#19
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
#20
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...
June 2017: Molecular Medicine Reports
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