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Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Francesca Galletta, Gennaro Riccio, Emanuela Esposito, Claudia De Lorenzo, Michelino De Laurentiis, Paolo Spallarossa, Giuseppe Mercuro
The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others...
May 2016: Journal of Cardiovascular Medicine
Takashi Umehara, Ikko Kawashima, Tomoko Kawai, Yumi Hoshino, Ken-Ichirou Morohashi, Yuichi Shima, Wenxian Zeng, JoAnne S Richards, Masayuki Shimada
Adult Leydig cells are derived from proliferating stem/progenitor Leydig cells in the infant testis and subsequent differentiation to steroidogenic cells in adult mice. Leydig cell proliferation in the infant testis occurs primarily in response to increased levels of LH that induce Leydig cell expression of neuregulin 1, NRG1. Depletion of NRG1 in Nrg1 mutant mice (Nrg1(flox;flox); Cyp19a1Cre mice) dramatically reduces Leydig cell proliferation in the infant testes leading to reduction of testis weight, epididymial weight and serum testosterone in the adult mutant mice...
October 12, 2016: Endocrinology
Michael S Fleming, Jian J Li, Daniel Ramos, Tong Li, David A Talmage, Shin-Ichi Abe, Silvia Arber, Wenqin Luo
: Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET(+) mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yanjun Sun, Taruna Ikrar, Melissa F Davis, Nian Gong, Xiaoting Zheng, Z David Luo, Cary Lai, Lin Mei, Todd C Holmes, Sunil P Gandhi, Xiangmin Xu
Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear...
October 5, 2016: Neuron
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
: : Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins...
September 14, 2016: Stem Cells Translational Medicine
Dong Hoon Shin, Donghoon Lee, Dong Wan Hong, Seung Hyun Hong, Jung-Ah Hwang, Byung Il Lee, Hye Jin You, Geon Kook Lee, In-Hoo Kim, Yeon-Su Lee, Ji-Youn Han
The neuregulin 1 (NRG1) fusion is a recently identified novel driver oncogene in invasive mucinous adenocarcinoma of the lung (IMA). After identification of a case of SLC3A2-NRG1 in a patient with IMA, we verified this fusion gene in a cohort of 59 patients with IMA. Targeted cancer panel sequencing and RT-PCR identified the possible coexistence of other driver oncogenes. Among 59 IMAs, we found 16 NRG1 fusions (13 SLC3A2-NRG1 and 3 CD74-NRG1). Of 16 patients with NRG1 fusions, concurrent KRAS codon 12 mutations were found in 10 cases...
September 8, 2016: Oncotarget
Benjamin M Schwenk, Hannelore Hartmann, Alperen Serdaroglu, Martin H Schludi, Daniel Hornburg, Felix Meissner, Denise Orozco, Alessio Colombo, Sabina Tahirovic, Meike Michaelsen, Franziska Schreiber, Simone Haupt, Michael Peitz, Oliver Brüstle, Clemens Küpper, Thomas Klopstock, Markus Otto, Albert C Ludolph, Thomas Arzberger, Peer-Hendrik Kuhn, Dieter Edbauer
Nuclear clearance of TDP-43 into cytoplasmic aggregates is a key driver of neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but the mechanisms are unclear. Here, we show that TDP-43 knockdown specifically reduces the number and motility of RAB11-positive recycling endosomes in dendrites, while TDP-43 overexpression has the opposite effect. This is associated with delayed transferrin recycling in TDP-43-knockdown neurons and decreased β2-transferrin levels in patient CSF Whole proteome quantification identified the upregulation of the ESCRT component VPS4B upon TDP-43 knockdown in neurons...
September 12, 2016: EMBO Journal
Colm M P O'Tuathaigh, Fabio Fumagalli, Lieve Desbonnet, Francesc Perez-Branguli, Gerard Moloney, Samim Loftus, Claire O'Leary, Emilie Petit, Rachel Cox, Orna Tighe, Gerard Clarke, Donna Lai, Richard P Harvey, John F Cryan, Kevin J Mitchell, Timothy G Dinan, Marco A Riva, John L Waddington
Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas...
September 9, 2016: Schizophrenia Bulletin
Lauren J Simmons, Monique C Surles-Zeigler, Yonggang Li, Gregory D Ford, Gale D Newman, Byron D Ford
BACKGROUND: We previously demonstrated that neuregulin-1 (NRG-1) was neuroprotective in rats following ischemic stroke. Neuroprotection by NRG-1 was associated with the suppression of pro-inflammatory gene expression in brain tissues. Over-activation of brain microglia can induce pro-inflammatory gene expression by activation of transcriptional regulators following stroke. Here, we examined how NRG-1 transcriptionally regulates inflammatory gene expression by computational bioinformatics and in vitro using microglial cells...
2016: Journal of Neuroinflammation
Shu Zhang, Seema Mukherjee, Xuejun Fan, Ahmad Salameh, Kalpana Mujoo, Zhao Huang, Leike Li, Georgina To'a Salazar, Ningyan Zhang, Zhiqiang An
HER3/ErbB3 has emerged as a new therapeutic target for cancer. Currently, more than a dozen anti-HER3 antibodies are in clinical trials for treatment of various cancers. However, limited understanding of the complex HER3 signaling in cancer and lack of established biomarkers have made it challenging to stratify cancer patients who can benefit from HER3 targeted therapies. In this study, we identified DJ-1/PARK7 (Parkinson Protein 7) as a novel interaction partner of HER3 and demonstrated the potential of DJ-1 as a biomarker for anti-HER3 cancer therapy...
August 25, 2016: Oncotarget
Hyunjeong Liew, Yun-Mi Kim, Hee Soon Choi, Ah Ram Jang, David Churchill, Sang Hyung Lee, Yoo-Hun Suh
Neuregulin-1 (NRG-1) is a ligand of the epidermal growth factor receptor (erbB), and its interaction involves activation of the glutamatergic N-methyl-D-aspartate receptor, which increases the expression of the β2 subunit of the γ-aminobutyric acid receptor and subunits of the nicotinic acetylcholine receptor. In the dentate gyrus of 14-month-old Tg2576 mice, NRG-1 was strongly expressed compared with age-matched controls. The supernatant of oligomeric amyloid β peptide (Aβ42)-treated glial cells enhanced the Aβ42-induced cytotoxic effects, but the expression of Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand in microglial cells was not changed upon cytotoxic treatment...
August 15, 2016: CNS & Neurological Disorders Drug Targets
Jiqing Xu, Fred de Winter, Catherine Farrokhi, Edward Rockenstein, Michael Mante, Anthony Adame, Jonathan Cook, Xin Jin, Eliezer Masliah, Kuo-Fen Lee
Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer's disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed...
2016: Scientific Reports
Hardeep S Gambhir, Eko Raharjo, Joanne Forden, Ranjan Kumar, Chinmaya Mishra, Gui Fang Guo, Joey Grochmal, Yuval Shapira, Rajiv Midha
BACKGROUND: To optimize survival evaluation of Schwann cells (SCs) in vivo, we tested fluorescent labeling of the nucleus as an improved method of tracking and counting the transplanted SCs at sciatic nerve injury sites in rodents. We also investigated if co-administering cells with the glial growth factor Neuregulin-1 β (NRG1β) improves in vivo survival. New Method We transduced SCs using a Lentiviral vector with a nuclear localization signal (NLS) fused with mCherry and transplanted them in the sciatic nerve of rat post-crush injury (bilateral) either in the presence or absence of NRG1β in the injectate media...
August 18, 2016: Journal of Neuroscience Methods
Antonio Jimeno, Jean-Pascal Machiels, Lori Wirth, Pol Specenier, Tanguy Y Seiwert, Feby Mardjuadi, Xiaodong Wang, Amy V Kapp, Stephanie Royer-Joo, Elicia Penuel, Bruce McCall, Andrea Pirzkall, Paul M Clement
BACKGROUND: This open-label, multicenter, phase Ib study assessed the safety and preliminary activity of duligotuzumab, a dual-action antibody that blocks ligand binding to human epidermal growth factor receptor 3 (HER3) and epidermal growth factor receptor, in combination with chemotherapy, in the first-line treatment of patients with recurrent/metastatic squamous cell cancer of the head and neck. METHODS: On day 1, duligotuzumab at a dose of 1650 mg intravenously was combined with cisplatin at a dose of 100 mg/m(2) and 5-fluorouracil at a dose of 1000 mg/m(2) /day on days 1 to 4 in treatment arm A, or carboplatin (area under the curve, 6 mg/mL/min) and paclitaxel (at a dose of 200 mg/m(2) ) in treatment arm B...
August 15, 2016: Cancer
David J Clarke, Jordyn Stuart, Iain S McGregor, Jonathon C Arnold
The endocannabinoid system is dysregulated in schizophrenia. Mice with heterozygous deletion of neuregulin 1 (Nrg1 HET mice) provide a well-characterised animal model of schizophrenia, and display enhanced sensitivity to stress and cannabinoids during adolescence. However, no study has yet determined whether these mice have altered brain endocannabinoid concentrations. Nrg1 application to hippocampal slices decreased 2-arachidonoylglycerol (2-AG) signalling and disrupted long-term depression, a form of synaptic plasticity critical to spatial learning...
January 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Qiong Jiang, Shuangxi Chen, Chengliang Hu, Peizhi Huang, Huifan Shen, Weijiang Zhao
Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop in the elderly, is characterized by the deposition of β‑amyloid protein (Aβ) and extensive neuronal cell death in the brain. Neuregulin‑1 (Nrg1)‑mediated intercellular and intracellular communication via binding to ErbB receptors regulates a diverse set of biological processes involved in the development of the nervous system. In the present study, a linear correlation was identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a human cortical tissue microarray...
September 2016: Molecular Medicine Reports
Ian Mahar, Angus MacIsaac, John Junghan Kim, Calvin Qiang, Maria Antonietta Davoli, Gustavo Turecki, Naguib Mechawar
Adult hippocampal neurogenesis is associated with learning and affective behavioural regulation. Its diverse functionality is segregated along the septotemporal axis from the dorsal to ventral hippocampus. However, features distinguishing immature neurons in these regions have yet to be characterized. Additionally, although we have shown that administration of the neurotrophic factor neuregulin-1 (NRG1) selectively increases proliferation and overall neurogenesis in the mouse ventral dentate gyrus (DG), likely through ErbB3, NRG1's effects on intermediate neurogenic stages in immature neurons are unknown...
2016: Scientific Reports
Renzo Mancuso, Anna Martínez-Muriana, Tatiana Leiva, David Gregorio, Lorena Ariza, Marta Morell, Jesús Esteban-Pérez, Alberto García-Redondo, Ana C Calvo, Gabriela Atencia-Cibreiro, Gabriel Corfas, Rosario Osta, Assumpció Bosch, Xavier Navarro
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motoneurons, which is preceded by loss of neuromuscular connections in a "dying back" process. Neuregulin-1 (Nrg1) is a neurotrophic factor essential for the development and maintenance of neuromuscular junctions, and Nrg1 receptor ErbB4 loss-of-function mutations have been reported as causative for ALS. Our main goal was to investigate the role of Nrg1 type I (Nrg1-I) in SOD1(G93A) mice muscles. We overexpressed Nrg1-I by means of an adeno-associated viral (AAV) vector, and investigated its effect by means of neurophysiological techniques assessing neuromuscular function, as well as molecular approaches (RT-PCR, western blot, immunohistochemistry, ELISA) to determine the mechanisms underlying Nrg1-I action...
November 2016: Neurobiology of Disease
Kathryn M Munro, Amelia Nash, Martina Pigoni, Stefan F Lichtenthaler, Jenny M Gunnersen
Inhibition of the protease β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a promising treatment strategy for Alzheimer's disease, and a number of BACE inhibitors are currently progressing through clinical trials. The strategy aims to decrease production of amyloid-β (Aβ) peptide from the amyloid precursor protein (APP), thus reducing or preventing Aβ toxicity. Over the last decade, it has become clear that BACE1 proteolytically cleaves a number of substrates in addition to APP. These substrates are not known to be involved in the pathogenesis of Alzheimer's disease but have other roles in the developing and/or mature central nervous system...
November 2016: Journal of Molecular Neuroscience: MN
Michael Willem
Neuregulin-1 (NRG1), known also as heregulin, acetylcholine receptor inducing activity (ARIA), glial growth factor (GGF), or sensory and motor neuron derived factor (SMDF), is a key factor for many developmental processes and in adult brain. All known splice variants contain an epidermal growth factor (EGF)-like domain, which is mediating signaling via receptors of the ErbB family. In particular, NRG1 acts as an essential signaling molecule expressed on the axonal surface, where it signals to Schwann cells throughout development and regulates the thickness of the myelin sheath...
July 5, 2016: Brain Research Bulletin
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