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https://www.readbyqxmd.com/read/29238610/a-role-for-erbb-signaling-in-the-induction-of-reactive-astrogliosis
#1
Jing Chen, Wanwan He, Xu Hu, Yuwen Shen, Junyan Cao, Zhengdong Wei, Yifei Luan, Li He, Fangdun Jiang, Yanmei Tao
Reactive astrogliosis is a hallmark of many neurological disorders, yet its functions and molecular mechanisms remain elusive. Particularly, the upstream signaling that regulates pathological responses of astrocytes is largely undetermined. We used a mouse traumatic brain injury model to induce astrogliosis and revealed activation of ErbB receptors in reactive astrocytes. Moreover, cell-autonomous inhibition of ErbB receptor activity in reactive astrocytes by a genetic approach suppressed hypertrophic remodeling possibly through the regulation of actin dynamics...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29237457/the-role-of-src-erk1-2-kinases-in-inspiratory-resistive-breathing-induced-acute-lung-injury-and-inflammation
#2
Dimitrios Toumpanakis, Vyronia Vassilakopoulou, Ioanna Sigala, Panagiotis Zacharatos, Ioanna Vraila, Vassiliki Karavana, Stamatios Theocharis, Theodoros Vassilakopoulos
BACKGROUND: Inspiratory resistive breathing (IRB), a hallmark of obstructive airway diseases, is associated with large negative intrathoracic pressures, due to strenuous contractions of the inspiratory muscles. IRB is shown to induce lung injury in previously healthy animals. Src is a multifunctional kinase that is activated in the lung by mechanical stress. ERK1/2 kinase is a downstream target of Src. We hypothesized that Src is activated in the lung during IRB, mediates ERK1/2 activation and IRB-induced lung injury...
December 13, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29237371/genetic-variability-of-src-family-kinases-and-its-association-with-platelet-hyperreactivity-and-clinical-outcomes-a-systematic-review
#3
Lukasz Milanowski, Fazila Rasul, Gajda Sylwia Natalia, Ceren Eyileten, Jolanta Siller-Matula, Marek Postula
BACKGROUND: Platelet hyperactivity has been implicated many cardiovascular (CV) events such as ischemic stroke, myocardial infarction and CV death. Genetic variability of platelet receptors has been shown to impact Src family kinases (SFKs) activation and in turn influence platelet activation. SFKs are important signal transmitters in platelets, interacting with several receptors as GPIIB/IIIa, GPIb, PEAR 1, GPIa, GPVI, PECAM and CD148. METHODS: In this review, we focused on genetic variants of platelet receptors whose signals are transmitted mainly by SFKs and may be associated with clinical manifestations of platelet hyperactivation like MI or IS...
December 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29234409/antcin-h-isolated-from-antrodia-cinnamomea-inhibits-renal-cancer-cell-invasion-partly-through-inactivation-of-fak-erk-c-ebp-%C3%AE-c-fos-mmp-7-pathways
#4
Kun-Yuan Chiu, Tzu-Hsiu Chen, Chi-Luan Wen, Jin-Mei Lai, Chi-Chih Cheng, Hsiang-Chun Liu, Shih-Lan Hsu, Yew-Min Tzeng
Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, Antrodia cinnamomea, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC50 value (for 48 h) was 170 μM. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 μM); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234114/probing-the-requirement-for-cd38-in-retinoic-acid-induced-hl-60-cell-differentiation-with-a-small-molecule-dimerizer-and-genetic-knockout
#5
Robert J MacDonald, Jonathan H Shrimp, Hong Jiang, Lu Zhang, Hening Lin, Andrew Yen
CD38 is an ectoenzyme and receptor with key physiological roles. It metabolizes NAD+ to adenosine diphosphate ribose (ADPR) and cyclic ADPR, regulating several processes including calcium signalling. CD38 is both a positive and negative prognostic indicator in leukaemia. In all-trans retinoic acid (RA)-induced differentiation of acute promyelocytic leukaemia and HL-60 cells, CD38 is one of the earliest and most prominently upregulated proteins known. CD38 overexpression enhances differentiation, while morpholino- and siRNA-induced knockdown diminishes it...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234112/a-switch-in-nucleotide-affinity-governs-activation-of-the-src-and-tec-family-kinases
#6
Freia von Raußendorf, Anita de Ruiter, Thomas A Leonard
The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. Whilst the Src and Abl kinases are regulated by tail phosphorylation and N-terminal myristoylation respectively, the Tec kinases are notable for the absence of either regulatory element. We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234062/development-of-erasin-a-chromone-based-stat3-inhibitor-which-induces-apoptosis-in-erlotinib-resistant-lung-cancer-cells
#7
Christian Lis, Stefan Rubner, Martin Roatsch, Angela Berg, Tyler Gilcrest, Darwin Fu, Elizabeth Nguyen, Anne-Marie Schmidt, Harald Krautscheid, Jens Meiler, Thorsten Berg
Inhibition of protein-protein interactions by small molecules offers tremendous opportunities for basic research and drug development. One of the fundamental challenges of this research field is the broad lack of available lead structures from nature. Here, we demonstrate that modifications of a chromone-based inhibitor of the Src homology 2 (SH2) domain of the transcription factor STAT5 confer inhibitory activity against STAT3. The binding mode of the most potent STAT3 inhibitor Erasin was analyzed by the investigation of structure-activity relationships, which was facilitated by chemical synthesis and biochemical activity analysis, in combination with molecular docking studies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29232409/lupeol-and-stigmasterol-suppress-tumor-angiogenesis-and-inhibit-cholangiocarcinoma-growth-in-mice-via-downregulation-of-tumor-necrosis-factor-%C3%AE
#8
Thaned Kangsamaksin, Supattra Chaithongyot, Chanida Wootthichairangsan, Rattanavinan Hanchaina, Chayada Tangshewinsirikul, Jisnuson Svasti
Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities and have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol and stigmasterol on tumor and endothelial cells in vitro and their anti-cancer activities in vivo. Our results demonstrated that lupeol and stigmasterol suppressed cell viability, migration, and morphogenesis of human umbilical vein endothelial cells (HUVECs) but not cholangiocarcinoma (CCA) cells...
2017: PloS One
https://www.readbyqxmd.com/read/29231998/phosphorylated-tyr142-%C3%AE-catenin-localizes-to-centrosomes-and-is-regulated-by-syk
#9
D Bhardwaj, M Náger, A Visa, M C Sallán, P J Coopman, C Cantí, J Herreros
β-catenin is a central component of adherent junctions and a key effector of canonical Wnt signalling, in which dephosphorylated Ser/Thr β-catenin regulates gene transcription. β-catenin phosphorylation at Tyr142 (PTyr142 β-catenin), which is induced by receptor and Src family Tyr kinases, represents a previously described β-catenin switch from adhesive to migratory roles. In addition to classical β-catenin roles, phosphorylated Ser/Thr β-catenin and total β-catenin were involved in centrosomal functions, including mitotic spindle formation and centrosome separation...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29231907/activated-hgf-c-met-axis-in-head-and-neck-cancer
#10
REVIEW
Levi Arnold, Jonathan Enders, Sufi Mary Thomas
Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent's pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal-epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy...
December 12, 2017: Cancers
https://www.readbyqxmd.com/read/29229683/mesenchymal-stem-cells-promote-endothelial-progenitor-cell-migration-vascularization-and-bone-repair-in-tissue-engineered-constructs-via-activating-cxcr2-src-pkl-vav2-rac1
#11
Zhilin Li, Aijun Yang, Xiaolong Yin, Shiwu Dong, Fei Luo, Ce Dou, Xu Lan, Zhao Xie, Tianyong Hou, Jianzhong Xu, Junchao Xing
Tissue-engineered constructs (TECs) hold great promise for treating large bone defects. Incorporated mesenchymal stem cells (MSCs) can facilitate the vascularization of TECs. Nevertheless, the underlying mechanism remains ambiguous. Here we analyzed the roles of C-X-C chemokine receptor 2 (CXCR2) and its downstream signal pathways in MSC-induced endothelial progenitor cell (EPC) migration. Transwell assays and immunofluorescence staining were performed for cell migration analysis in vitro and in vivo, respectively...
December 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29229632/activation-of-the-aryl-hydrocarbon-receptor-leads-to-resistance-to-egfr-tkis-in-non-small-cell-lung-cancer-by-activating-src-mediated-bypass-signaling
#12
Mingxiang Ye, Yong Zhang, Hongjun Gao, Yan Xu, Pengyu Jing, Jianxiong Wu, Xinxin Zhang, Jie Xiong, Chenfang Dong, Libo Yao, Jian Zhang, Jian Zhang
PURPOSE: The aryl hydrocarbon receptor (AhR) has been generally recognized as a ligand-activated transcriptional factor that responds to xenobiotic chemicals. Recent studies have suggested that the expression of AhR varies widely across different cancer types and cancer cell lines, but its significance in cancer treatment has yet to be clarified. EXPERIMENTAL DESIGN: AhR expression in non-small-cell lung cancer (NSCLC) was determined by Western blotting and IHC staining...
December 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29228862/oculomotor-cognitive-control-abnormalities-in-australian-rules-football-players-with-a-history-of-concussion
#13
Meaghan Clough, Steven Mutimer, David K Wright, Adrian Tsang, Daniel Costello, Andrew Gardner, Peter Stanwell, Richelle Mychasiuk, Mujun Sun, Rhys D Brady, Stuart John McDonald, Kyria Maree Webster, Maddison Johnstone, Joanne Fielding, Bridgette Semple, Denes V Agoston, Owen B White, Richard Frayne, Terence John O'Brien, Sandy Richard Shultz
This study used oculomotor, cognitive, and multimodal magnetic resonance imaging (MRI) measures to assess for neurological abnormalities in current asymptomatic amateur Australian rules footballers (i.e., Australia's most participated collision sport) with a history of sports-related concussion (SRC). Participants were 15 male amateur Australian rules football players with a history of SRC greater than 6 months previously, and 15 sex-, age- and education-matched athlete control subjects that had no history of neurotrauma or participation in collision sports...
December 11, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29228573/pnma5-is-essential-to-the-progression-of-meiosis-in-mouse-oocytes-through-a-chain-of-phosphorylation
#14
Xiao-Lan Zhang, Peng Liu, Zhi-Xia Yang, Jing-Jing Zhao, Lei-Lei Gao, Bo Yuan, Li-Ya Shi, Chun-Xiang Zhou, Hai-Feng Qiao, Ya-Hong Liu, Xiao-Yan Ying, Jun-Qiang Zhang, Xiu-Feng Ling, Dong Zhang
PNMA (paraneoplastic antigen MA) family includes Pnma1-6. Although other members have been found to be involved in paraneoplastic neurological disorders, death receptor-dependent apoptosis, and tumorigenesis, Pnma5 was thought to be a female fertility factor, as indicated by one genome-wide study. But until now there have not been any further functional studies about Pnma5 in female meiosis. Our preliminary study indicated that Pnma5 might play important roles in meiosis. To further address this, Pnma5 was knocked down in in-vitro maturated (IVM) mouse oocytes, which are common models for mammalian female meiosis, by specific siRNA, and results showed that the loss of Pnma5 significantly delayed the progression of meiosis I and increased chromosome segregation errors during anaphase I...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228424/circulating-ship2-mrna-as-a-novel-biomarker-in-the-diagnosis-and-prognosis-of-gastric-cancer
#15
J-F Xie, N-S Xie, J-H Tang, Q-P Gu, Q-T Luo
OBJECTIVE: Previous studies showed the aberrant expression of Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) in GC tissue. However, the exact role of circulating SHIP2 in GC remains unclear. The aim of this manuscript was to analyze potential diagnostic and prognostic value of circulating SHIP2 levels in GC. PATIENTS AND METHODS: Circulating SHIP2 expression was detected in the plasma of 156 GC patients and 60 healthy controls by qRT-PCR. The receiver operating characteristic (ROC) curves were plotted to explore the reliability of circulating SHIP2 in detecting GC...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29228131/synaptic-potentiation-at-basal-and-apical-dendrites-of-hippocampal-pyramidal-neurons-involves-activation-of-a-distinct-set-of-extracellular-and-intracellular-molecular-cues
#16
Patrycja Brzdak, Olga Wójcicka, Monika Zareba-Koziol, Daniel Minge, Christian Henneberger, Jakub Wlodarczyk, Jerzy W Mozrzymas, Tomasz Wójtowicz
In the central nervous system, several forms of experience-dependent plasticity, learning and memory require the activity-dependent control of synaptic efficacy. Despite substantial progress in describing synaptic plasticity, mechanisms related to heterogeneity of synaptic functions at local circuits remain elusive. Here we studied the functional and molecular aspects of hippocampal circuit plasticity by analyzing excitatory synapses at basal and apical dendrites of mouse hippocampal pyramidal cells (CA1 region) in acute brain slices...
December 8, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29227280/proapoptotic-puma-targets-stem-like-breast-cancer-cells-to-suppress-metastasis
#17
Qi Sun, Jacqueline Lesperance, Hiromi Wettersten, Elaine Luterstein, Yoko S DeRose, Alana Welm, David A Cheresh, Jay S Desgrosellier
Breast cancer cells with stem cell properties are key contributors to metastatic disease, and there remains a need to better understand and target these cells in human cancers. Here, we identified rare stem-like cells in patients' tumors characterized by low levels of the proapoptotic molecule p53-upregulated modulator of apoptosis (PUMA) and showed that these cells play a critical role in tumor progression that is independent of clinical subtype. A signaling axis consisting of the integrin αvβ3, Src kinase, and the transcription factor Slug suppresses PUMA in these cells, promoting tumor stemness...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29225564/revealing-the-radial-effect-on-orientation-discrimination-by-manual-reaction-time
#18
Lixin Liang, Yang Zhou, Mingsha Zhang, Yujun Pan
It has been shown that the sensitivity and accuracy of orientation perception in the periphery is significantly better when the orientations are radial with respect to the fixation point than when they are tangential. However, since perception and action may be dissociated, it is unclear whether the perceptual radial effect has a counterpart in reaction time (RT) of motor responses. Furthermore, it is unknown whether or how stimulus-response-compatibility (SRC) effect interacts with the radial effect to determine RT...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29225458/antiangiogenic-effect-of-dasatinib-in-murine-models-of-oxygen-induced-retinopathy-and-laser-induced-choroidal-neovascularization
#19
Songyi Seo, Wonhee Suh
Purpose: Vascular endothelial growth factor (VEGF) is a principal mediator of pathological ocular neovascularization, which is the leading cause of blindness in various ocular diseases. As Src, a non-receptor tyrosine kinase, has been implicated as one of the major signaling molecules in VEGF-mediated neovascularization, the present study aimed to investigate whether dasatinib, a potent Src kinase inhibitor, could suppress pathological ocular neovascularization in murine models of oxygen-induced retinopathy (OIR) and choroidal neovascularization (CNV)...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29224511/measuring-and-improving-student-engagement-in-clinical-training
#20
Simin Lee, Yannis K Valtis, Tomi Jun, David Wang, Biqi Zhang, Esther H Chung, Amy Yu, Rachael Williams, Marya J Cohen
Purpose Volunteer service learning activities, including Student Run Clinics (SRCs), are becoming an increasingly popular extracurricular component of medical education. While there are reports that student clinicians generally enjoy their educational experiences at SRCs, it is not understood how to optimize and measure student engagement in them. To identify key drivers of student engagement a tool was created to measure volunteer experience at the Crimson Care Collaborative (CCC), a primary care SRC. Methods CCC volunteers were asked to complete an online engagement survey...
December 11, 2017: Education for Primary Care
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