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https://www.readbyqxmd.com/read/29792166/the-pdgfr%C3%AE-erk1-2-pathway-regulates-cdcp1-expression-in-triple-negative-breast-cancer
#1
Luca Forte, Federica Turdo, Cristina Ghirelli, Piera Aiello, Patrizia Casalini, Marilena Valeria Iorio, Elvira D'Ippolito, Patrizia Gasparini, Roberto Agresti, Beatrice Belmonte, Gabriella Sozzi, Lucia Sfondrini, Elda Tagliabue, Manuela Campiglio, Francesca Bianchi
BACKGROUND: CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. METHODS: The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29790746/neuroprotective-compound-from-an-endophytic-fungus-colletotrichum-sp-js-0367
#2
Ji Hoon Song, Changyeol Lee, Dahae Lee, Soonok Kim, Sunghee Bang, Myoung-Sook Shin, Jun Lee, Ki Sung Kang, Sang Hee Shim
Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate...
May 23, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29789792/remote-ischemic-postconditioning-protects-against-myocardial-ischemia-reperfusion-injury-by-inhibition-of-the-rage-hmgb1-pathway
#3
Xiangming Wang, Junhong Wang, Tiantian Tu, Zakaria Iyan, Deeraj Mungun, Zhijian Yang, Yan Guo
Background: The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Methods: Mice model of MIRI was established and randomly divided into three groups: control group, ischemia reperfusion group, and remote ischemic postconditioning group. Infarction size was detected by Evans blue and TTC staining. Cardiac function was detected by echocardiography measurement...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29789577/long-non-coding-rna-gm2199-rescues-liver-injury-and-promotes-hepatocyte-proliferation-through-the-upregulation-of-erk1-2
#4
Qiang Gao, Yunyan Gu, Yanan Jiang, Li Fan, Zixiang Wei, Haobin Jin, Xirui Yang, Lijuan Wang, Xuguang Li, Sheng Tai, Baofeng Yang, Yan Liu
Long non-coding RNAs (lncRNAs) are a new class of regulators of various human diseases. This study was designed to explore the potential role of lncRNAs in experimental hepatic damage. In vivo hepatic damage in mice and in vitro hepatocyte damage in AML12 and NCTC1469 cells were induced by carbon tetrachloride (CCl4 ) treatments. Expression profiles of lncRNAs and mRNAs were analyzed by microarray. Bioinformatics analyses were conducted to predict the potential functions of differentially expressed lncRNAs with respect to hepatic damage...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29788264/mpk-1-erk-pathway-regulates-dna-damage-response-during-development-through-daf-16-foxo
#5
Julien N Bianco, Björn Schumacher
Ultraviolet (UV) induces distorting lesions to the DNA that can lead to stalling of the RNA polymerase II (RNAP II) and that are removed by transcription-coupled nucleotide excision repair (TC-NER). In humans, mutations in the TC-NER genes CSA and CSB lead to severe postnatal developmental defects in Cockayne syndrome patients. In Caenorhabditis elegans, mutations in the TC-NER genes csa-1 and csb-1, lead to developmental growth arrest upon UV treatment. We conducted a genetic suppressor screen in the nematode to identify mutations that could suppress the developmental defects in csb-1 mutants...
May 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29788096/pnaktide-ameliorates-renal-interstitial-fibrosis-through-inhibition-of-sodium-potassium-adenosine-triphosphatase-mediated-signaling-pathways-in-unilateral-ureteral-obstruction-mice
#6
Xi Cheng, Yi Song, Yu Wang
Background: Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been shown to regulate Src activity by combining with Src to keep it in an inactive form. We previously reported that Na/K-ATPase was downregulated in unilateral ureteral obstruction (UUO) animals. In this study, we examined whether inhibition of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial fibrosis induced by UUO. Methods: UUO was performed on male C57BL/6J mice...
May 17, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29787986/anti-inflammatory-effects-and-mechanism-of-the-total-flavonoids-from-artemisia-scoparia-waldst-et-kit-in-vitro-and-in-vivo
#7
Xue Wang, Hua Huang, Xueping Ma, Linlin Wang, Chong Liu, Biyu Hou, Shengqian Yang, Li Zhang, Guanhua Du
Artemisia scoparia Waldst. et Kit. is traditionally used for the treatment of jaundice urinary retention, itching wet sores, infectious icteric hepatitis and influenza in Uighur medicine. This study aimed to further illuminate the anti-inflammatory effects and mechanism of the total flavonoids (ASTF) from Artemisia scoparia Waldst. et Kit. In vitro, RAW 264.7 cells were pretreated with ASTF 1 h before stimulation with LPS (1 μg/mL) for 24 h. Then, the concentrations of NO, PGE2 , TNF-α, IL-6 and MCP-1 in the medium were determined...
May 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29786867/growth-hormone-releasing-hormone-antagonists-reduce-prostatic-enlargement-and-inflammation-in-carrageenan-induced-chronic-prostatitis
#8
Petra Popovics, Renzhi Cai, Wei Sha, Ferenc G Rick, Andrew V Schally
BACKGROUND: Inflammation plays a key role in the etiology of benign prostatic hyperplasia (BPH) through multiple pathways involving the stimulation of proliferation by cytokines and growth factors as well as the induction of the focal occurrence of epithelial-to-mesenchymal transition (EMT). We have previously reported that GHRH acts as a prostatic growth factor in experimental BPH and in autoimmune prostatitis models and its blockade with GHRH antagonists offer therapeutic approaches for these conditions...
May 21, 2018: Prostate
https://www.readbyqxmd.com/read/29783779/hyperoxia-disrupts-extracellular-signal-regulated-kinases-1-2-induced-angiogenesis-in-the-developing-lungs
#9
Renuka T Menon, Amrit Kumar Shrestha, Roberto Barrios, Binoy Shivanna
Hyperoxia contributes to the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of infants that is characterized by interrupted alveologenesis. Disrupted angiogenesis inhibits alveologenesis, but the mechanisms of disrupted angiogenesis in the developing lungs are poorly understood. In pre-clinical BPD models, hyperoxia increases the expression of extracellular signal-regulated kinases (ERK) 1/2; however, its effects on the lung endothelial ERK1/2 signaling are unclear. Further, whether ERK1/2 activation promotes lung angiogenesis in infants is unknown...
May 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29782313/kainic-acid-impairs-the-memory-behavior-of-app23-mice-by-increasing-brain-amyloid-load-through-a-tumor-necrosis-factor-%C3%AE-dependent-mechanism
#10
Yang Ruan, Shi-Jie Guo, Xu Wang, Dong Dong, Dong-Hui Shen, Jie Zhu, Xiang-Yu Zheng
Kainic acid (KA) was recently identified as an epileptogenic and neuroexcitotoxic agent that is responsible for inducing learning and memory deficits in various neurodegenerative diseases, such as Alzheimer's disease (AD). However, the mechanism by which KA acts upon AD remains unclear. To this end, we presently investigated the roles of KA in processing amyloid-β protein precursor (AβPP) and amyloid-β protein (Aβ) loads during the course of AD development and progression. Specifically, KA treatment clearly caused the upregulation of tumor necrosis factor α (TNF-α) via activation of the PI3-K/AKT, ERK1/2, and p65 pathways in glial cells...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29779473/activation-of-the-cxcl16-cxcr6-axis-by-tnf-%C3%AE-contributes-to-ectopic-endometrial-stromal-cells-migration-and-invasion
#11
Yaoming Peng, Junyan Ma, Jun Lin
The activation of systemic and local inflammatory mechanisms, including elevated levels of chemokines and proinflammatory cytokines in endometriosis progression, is becoming more evident in the recent years. Here, we report the involvement of CXC chemokine 16 (CXCL16) and its sole receptor, CXC chemokine receptor 6 (CXCR6), in pathophysiology of endometriosis. Expression of CXCL16, but not CXCR6, was significantly upregulated in endometriotic lesions when compared to control endometrium. Additionally, serum CXCL16 was significantly elevated in women with endometriosis when compared to control group...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29778778/swimming-improves-cognitive-reserve-in-ovariectomized-rats-and-enhances-neuroprotection-after-global-cerebral-ischemia
#12
Meng Zhang, Yating Zhai, Yaping Sun, Wenli Zhang, Qian Li, Darrell Brann, Ruimin Wang
Cognitive reserve has been proposed to account for different responses to brain damage or pathology. Factors implicated to influence cognitive reserve include cognitive engagement, physical activity, leisure activities, stress levels, and diet. Furthermore, long-term ovariectomy (OVX), such as occurs in women that have underwent surgical menopause, has been reported to increase the risk of cognitive impairment. In the current study, we examined whether swimming improves cognitive function in long-term OVX-rats...
May 17, 2018: Brain Research
https://www.readbyqxmd.com/read/29778748/protein-kinases-are-involved-in-the-cardioprotective-effects-activated-by-platelet-glycoprotein-iib-iiia-inhibitor-tirofiban-at-reperfusion-in-rats-in-vivo
#13
Shih-Tai Chang, Ya-Ting Yang, Chi-Ming Chu, Kuo-Li Pan, Jen-Te Hsu, Ju-Feng Hsiao, Yu-Sheng Lin, Chang-Min Chung
The thrombolytic effect of platelet glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa inhibitors) in myocardial infarction has been well established. Nevertheless, data on the mechanism of the cardioprotective effect of GP IIb/IIIa inhibitors in ischemic-reperfusion injury (IR) are lacking. Sprague-Dawley rats received 120min of coronary ischemia and 180min of reperfusion. A GP IIb/IIIa inhibitor was given via continuous intravenous infusion at a rate of 2 ug/kg/min 30min prior to reperfusion with/without inhibitors of PKCε (chelerythrine), PI3 kinase and Akt (wortmannin), p38 MAPK (SB203582), p42/44 MAPK (PD98059) and ERK1/2 (u0126) 15min prior to the GP IIb/IIIa inhibitor...
May 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29778505/novel-peptide-nanoparticle-biased-antagonist-of-ccr3-blocks-eosinophil-recruitment-and-airway-hyperresponsiveness
#14
Milica Grozdanovic, Kimberly G Laffey, Hazem Abdelkarim, Ben Hitchinson, Anantha Harijith, Hyung-Geon Moon, Gye Young Park, Lee K Rousslang, Joanne C Masterson, Glenn T Furuta, Nadya I Tarasova, Vadim Gaponenko, Steven J Ackerman
BACKGROUND: Chemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason may be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance. OBJECTIVE: We sought to develop a novel peptide nanoparticle CCR3 inhibitor (R321) with a biased mode of inhibition that would block G-protein signaling, but enable or promote receptor internalization...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29778459/bisphenol-a-inhibits-improvement-of-testosterone-in-anxiety-and-depression-like-behaviors-in-gonadectomied-male-mice
#15
Yvfeng Liang, Jiahong Li, Tao Jin, Ting Gu, Qingjie Zhu, Yizhong Hu, Yang Yang, Jisui Li, Donghong Wu, Kesheng Jiang, Xiaohong Xu
Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice...
May 17, 2018: Hormones and Behavior
https://www.readbyqxmd.com/read/29777777/mir-128-3p-directly-targets-vegfc-vegfr3-to-modulate-the-proliferation-of-lymphatic-endothelial-cells-through-ca-2-signaling
#16
Jie Zhou, Zhiyou He, Le Guo, Jizhang Zeng, Pengfei Liang, Licheng Ren, Minghua Zhang, Pihong Zhang, Xiaoyuan Huang
Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation...
May 16, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29777684/repositioning-of-anti-cancer-drug-candidate-azd7762-to-an-anti-allergic-drug-suppressing-ige-mediated-mast-cells-and-allergic-responses-via-the-inhibition-of-lyn-and-fyn
#17
Young Hwan Park, Do Kyun Kim, Hyun Woo Kim, Hyuk Soon Kim, Dajeong Lee, Min Bum Lee, Keun Young Min, Jimo Koo, Su Jeong Kim, Changhee Kang, Young Mi Kim, Hyung Sik Kim, Wahn Soo Choi
Mast cells are critical effector cells in IgE-mediated allergic responses. The aim of this study was to investigate the anti-allergic effects of 3-[(aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-thiophenecarboxamide (AZD7762) in vitro and in vivo. AZD7762 inhibited the antigen-stimulated degranulation from RBL-2H3 (IC50 , ∼ 27.9 nM) and BMMCs (IC50 , ∼ 99.3 nM) in a dose-dependent manner. AZD7762 also inhibited the production of TNF-α and IL-4. As the mechanism of its action, AZD7762 inhibited the activation of Syk and its downstream signaling proteins, such as Linker of activated T cells (LAT), phospholipase (PL) Cγ1, Akt, and mitogen-activated protein (MAP) kinases (Erk1 / 2, p38, and JNK) in mast cells...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29777374/the-tenascin-c-derived-peptide-vswrapta-promotes-neuronal-branching-via-transcellular-activation-of-the-focal-adhesion-kinase-fak-and-the-erk1-2-signaling-pathway-in-vitro
#18
Marvin Jarocki, Omar Sallouh, Ralf Weberskirch, Andreas Faissner
The central nervous system (CNS) of mammals has a limited regeneration capacity after traumatic events, which causes chronic functional disability. The development of biomaterials aims at providing support for the regeneration process. One strategy integrates peptides that mimic functional domains of extracellular matrix (ECM) or cell adhesion molecules with synthetic polymers designed to present growth-supporting cues to the neuronal microenvironment. Thus, small peptide sequences originating from molecules of the ECM may serve as promising bio-additives, acting as artificial matricryptins to gear cellular processes...
May 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29775898/particle-induced-sirt1-downregulation-promotes-osteoclastogenesis-and-osteolysis-through-er-stress-regulation
#19
Liang Zhang, Dongmei Bao, Peng Li, Zhidong Lu, Long Pang, Zhirong Chen, Haohui Guo, Zhihui Gao, Qunhua Jin
BACKGROUND: Sirtuin 1 (SIRT1) downregulation has been found to be induced by wear particles in aseptic prosthesis loosening (APL). Osteoclastogenesis and osteoclast activation are the main pathological factors associated with APL. However, whether SIRT1 downregulation contributes to the formation and activation of osteoclasts through the induction of endoplasmic reticulum (ER) stress is unclear. METHODS: To address this, an osteolysis mouse model was used in which animals were treated with the SIRT1 activator, resveratrol (RES), or an ER stress inhibitor, 4-PBA, for two weeks...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775310/fragment-based-discovery-of-a-potent-orally-bioavailable-inhibitor-which-modulates-the-phosphorylation-and-catalytic-activity-of-erk1-2
#20
Tom D Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Maria Buck, Megan Cassidy, Juan Castro, Aurelie Courtin, James E H Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte M Griffiths-Jones, John F Lyons, Vanessa Martins, Sandra Muench, Joanne M Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Michael Reader, David C Rees, Sharna J Rich, Caroline Richardson, Harpreet Saini, Neil T Thompson, Nicola G Wallis, Hugh Walton, Nicola E Wilsher, Alison J-A Woolford, Michael Cooke, David Cousin, Stuart Onions, Jonathan Shannon, John Watts, Christopher W Murray
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signalling through ERK1/2. Here we describe the fragment based generation of ERK1/2 inhibitors which block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity...
May 18, 2018: Journal of Medicinal Chemistry
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