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https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#1
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28212927/patients-with-chronic-dizziness-following-traumatic-head-injury-typically-have-multiple-diagnoses-involving-combined-peripheral-and-central-vestibular-dysfunction
#2
Q Arshad, R E Roberts, H Ahmad, R Lobo, M Patel, T Ham, D J Sharp, B M Seemungal
OBJECTIVE: We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted...
February 7, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28212542/two-stage-genome-wide-association-study-identifies-a-novel-susceptibility-locus-associated-with-melanoma
#3
Katherine J Ransohoff, Wenting Wu, Hyunje G Cho, Harvind C Chahal, Yuan Lin, Hong-Ji Dai, Christopher I Amos, Jeffrey E Lee, Jean Y Tang, David A Hinds, Jiali Han, Qingyi Wei, Kavita Y Sarin
Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208971/a-rare-association-of-pentalogy-of-fallot-with-situs-inversus-totalis-complicated-by-brain-abscess-in-an-adolescent-case-report
#4
Muhammed Basheer, Sunil Kumar Agarwalla
Tetralogy of Fallot (TOF) is the most frequently diagnosed congenital cyanotic heart disease. It is often associated with additional findings, such as atrial septal defect (i.e., pentalogy of Fallot) or right sided aortic arch. Association of this pentalogy of Fallot with situs inversus totalis is rarely reported in paediatric literature and it can cause technical challenges to intracardiac repair. We report the case of pentalogy of Fallot with dextrocardia and situs inversus presenting as parieto-occipital abscess in a 12-year-old child...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28198124/long-distance-axonal-growth-and-protracted-functional-maturation-of-neurons-derived-from-human-induced-pluripotent-stem-cells-after-intracerebral-transplantation
#5
Jonathan C Niclis, Christopher Turner, Jennifer Durnall, Stuart McDougal, Jessica A Kauhausen, Bryan Leaw, Mirella Dottori, Clare L Parish, Lachlan H Thompson
The capacity for induced pluripotent stem (iPS) cells to be differentiated into a wide range of neural cell types makes them an attractive donor source for autologous neural transplantation therapies aimed at brain repair. Translation to the in vivo setting has been difficult, however, with mixed results in a wide variety of preclinical models of brain injury and limited information on the basic in vivo properties of neural grafts generated from human iPS cells. Here we have generated a human iPS cell line constitutively expressing green fluorescent protein as a basis to identify and characterize grafts resulting from transplantation of neural progenitors into the adult rat brain...
February 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28196356/therapeutic-hypothermia-provides-variable-protection-against-behavioral-deficits-after-neonatal-hypoxia-ischemia-a-potential-role-for-brain-derived-neurotrophic-factor
#6
Johana Diaz, Suleiman Abiola, Nancy Kim, Oliver Avaritt, Debra Flock, Jenny Yu, Frances J Northington, Raul Chavez-Valdez
BACKGROUND: Despite treatment with therapeutic hypothermia (TH), infants who survive hypoxic ischemic (HI) encephalopathy (HIE) have persistent neurological abnormalities at school age. Protection by TH against HI brain injury is variable in both humans and animal models. Our current preclinical model of hypoxia-ischemia (HI) and TH displays this variability of outcomes in neuropathological and neuroimaging end points with some sexual dimorphism. The detailed behavioral phenotype of this model is unknown...
February 15, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28188802/crosstalk-of-metabolic-factors-and-neurogenic-signaling-in-adult-neurogenesis-implication-of-metabolic-regulation-for-mental-and-neurological-diseases
#7
Chong Gao, Qi Wang, Sookja K Chung, Jiangang Shen
Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect adult neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases. Adult neurogenesis contains multiple steps including proliferation of neural stem cells, lineage commitments of neural progenitor cells, maturation into functional neurons, and integration into neuronal network. Many intrinsic and extrinsic factors produced from neural stem/progenitor cells and their microenvironment or neurogenic niche take roles in modulating neurogenesis and contribute to the brain repair and functional recoveries in many neurological diseases and psychiatric disorders...
February 7, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28186348/transplantation-with-hypoxia-preconditioned-mesenchymal-stem-cells-suppresses-brain-injury-caused-by-cardiac-arrest-induced-global-cerebral-ischemia-in-rats
#8
Ji-Wen Wang, Yu-Ru Qiu, Yue Fu, Jun Liu, Zhi-Jie He, Zi-Tong Huang
Cardiac arrest-induced global cerebral ischemia is a main cause of neurological dysfunction in emergency medicine. Transplantation with bone marrow mesenchymal stem cells (MSCs) has been used in stroke models to repair the ischemic brain injury, but it is little studied in models with global cerebral ischemia. In the present study, a hypoxia precondition was used to improve the efficacy of MSC transplantation, given the low survival and migration rates and limited differentiation capacities of MSCs. We found that hypoxia can increase the expansion and migration of MSCs by activating the PI3K/AKT and hypoxia-inducible factor-1α/CXC chemokine receptor-4 pathways...
February 10, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28186177/the-far-reaching-scope-of-neuroinflammation-after-traumatic-brain-injury
#9
REVIEW
Dennis W Simon, Mandy J McGeachy, Hülya Bayır, Robert S B Clark, David J Loane, Patrick M Kochanek
The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration...
February 10, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28185119/biallelic-brca2-mutations-in-two-black-south-african-children-with-fanconi-anaemia
#10
Candice Feben, Careni Spencer, Anneline Lochan, Nakita Laing, Karen Fieggen, Engela Honey, Tasha Wainstein, Amanda Krause
Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition, characterized cytogenetically by chromosomal instability and breakage secondary to impaired DNA repair mechanisms. Affected individuals typically manifest growth restriction and congenital physical abnormalities and most progress to hematological disease including bone marrow aplasia. A rare genetic subtype of FA (FA-D1) is caused by biallelic mutations in the BRCA2 gene. Affected individuals manifest severe congenital anomalies and significant pigmentary changes and are additionally at risk for early onset leukemia and certain solid organ malignancies, including Wilms tumors and brain tumors...
February 9, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28182332/challenging-the-great-vascular-wall-can-we-envision-a-simple-yet-comprehensive-therapy-for-stroke
#11
Marta Machado-Pereira, Tiago Santos, Lino Ferreira, Liliana Bernardino, Raquel Ferreira
Stroke is a leading cause of death in adult life, closely behind ischemic heart disease, and causes a significant and abiding socioeconomic burden. However, current therapies are not able to ensure full neurologic and/or sequelae-free recovery to all stroke survivors. We believe treatment efficacy and patient rehabilitation could be enhanced significantly by targeting blood-brain barrier (BBB) deregulation and inflammation-induced barrier loss occurring after stroke. In this pathological context, bone marrow-derived endothelial progenitor cells (EPC) enter the bloodstream towards the lesion site but their insufficient numbers and impaired angiogenic ability compromise neurovascular regeneration...
February 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28181563/the-antimicrobial-molecule-trappin-2-elafin-has-anti-parasitic-properties-and-is-protective-in-vivo-in-a-murine-model-of-cerebral-malaria
#12
Christian Roussilhon, Gilles Bang, Fabien Bastaert, Brigitte Solhonne, Ignacio Garcia-Verdugo, Roger Peronet, Pierre Druilhe, Anavaj Sakuntabhai, Salaheddine Mecheri, Jean-Michel Sallenave
According to the WHO, and despite reduction in mortality rates, there were an estimated 438 000 malaria deaths in 2015. Therefore new antimalarials capable of limiting organ damage are still required. We show that systemic and lung adenovirus (Ad)-mediated over-expression of trappin-2 (T-2) an antibacterial molecule with anti-inflammatory activity, increased mice survival following infection with the cerebral malaria-inducing Plasmodium berghei ANKA (PbANKA) strain. Systemically, T-2 reduced PbANKA sequestration in spleen, lung, liver and brain, associated with a decrease in pro-inflammatory cytokines (eg TNF-α in spleen and lung) and an increase in IL-10 production in the lung...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181357/post-embryonic-fish-brain-proliferation-zones-exhibit-neuroepithelial-type-gene-expression-profile
#13
E Dambroise, M Simion, T Bourquard, S Bouffard, B Rizzi, Y Jaszczyszyn, M Bourge, P Affaticati, A Heuzé, J Jouralet, J Edouard, S Brown, C Thermes, A Poupon, E Reiter, F Sohm, F Bourrat, J-S Joly
In mammals, neuroepithelial cells play an essential role in embryonic neurogenesis, whereas glial stem cells are the principal source of neurons at post-embryonic stages. By contrast, neuroepithelial-like stem/progenitor (NE) cells have been shown to be present throughout life in teleosts. We used 3-dimensional (3D) reconstructions of cleared transgenic wdr12:GFP medaka brains to demonstrate that this cell type is widespread in juvenile and to identify new regions containing NE cells. We established the gene expression profile of optic tectum (OT) NE cells by cell sorting followed by RNA-seq...
February 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28161197/icariin-enhances-remyelination-process-after-acute-demyelination-induced-by-cuprizone-exposure
#14
Yifan Zhang, Linlin Yin, Na Zheng, Li Zhang, Jianghong Liu, Weixiong Liang, Qi Wang
Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal...
February 1, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28160757/biochemistry-and-neuroscience-the-twain-need-to-meet
#15
REVIEW
Mary B Kennedy
Neuroscience has come to mean the study of electrophysiology of neurons and synapses, micro and macro-scale neuroanatomy, and the functional organization of brain areas. The molecular axis of the field, as reflected in textbooks, often includes only descriptions of the structure and function of individual channels and receptor proteins, and the extracellular signals that guide development and repair. Studies of cytosolic 'molecular machines', large assemblies of proteins that orchestrate regulation of neuronal functions, have been neglected...
February 1, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28159699/drugs-targeting-intermediate-filaments-can-improve-neurosupportive-properties-of-astrocytes
#16
Yolanda de Pablo, Meng Chen, Elin Möllerström, Marcela Pekna, Milos Pekny
In response to central nervous system (CNS) injury, astrocytes upregulate intermediate filament (nanofilament) proteins GFAP and vimentin. Whereas the intermediate filament upregulation in astrocytes is important for neuroprotection in the acute phase of injury, it might inhibit the regenerative processes later on. Thus, timely modulation of the astrocyte intermediate filaments was proposed as a strategy to promote brain repair. We used clomipramine, epoxomicin and withaferin A, drugs reported to decrease the expression of GFAP, and assessed their effect on neurosupportive properties and resilience of astrocytes to oxygen and glucose deprivation (OGD)...
January 31, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28159330/neurosurgery-of-the-future-deep-brain-stimulations-and-manipulations
#17
Stylianos Nicolaidis
Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technology will make both DBS and DBM more precise as procedures and will broaden their indications. CLDBS utilizes as feedback a variety of sources of electrophysiological and neurochemical afferent information about the function of the brain structures to be treated or studied...
January 11, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28155808/using-electrical-stimulation-to-enhance-the-efficacy-of-cell-transplantation-therapies-for-neurodegenerative-retinal-diseases-concepts-challenges-and-future-perspectives
#18
Abby Leigh Manthey, Wei Liu, Zhi Xin Jiang, Marcus Hiu Kong Lee, Jian Ji, Kwok-Fai So, Jimmy Shiu Ming Lai, Vincent Wing Hong Lee, Kin Chiu
Disease or trauma-induced loss or dysfunction of neurons in any central nervous system (CNS) tissue will have a significant impact on the health of the affected patient. The retina is a multilayered tissue that originates from the neuroectoderm, much like the brain and spinal cord. While sight is not required for life, neurodegeneration-related loss of vision not only affects the quality of life for the patient, but also has societal implications in terms of health care expenditure. Thus, it is essential to develop effective strategies to repair the retina and prevent disease symptoms...
February 3, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28153772/%C3%AE-1-integrin-signaling-promotes-neuronal-migration-along-vascular-scaffolds-in-the-post-stroke-brain
#19
Teppei Fujioka, Naoko Kaneko, Itsuki Ajioka, Kanako Nakaguchi, Taichi Omata, Honoka Ohba, Reinhard Fässler, José Manuel García-Verdugo, Kiyotoshi Sekiguchi, Noriyuki Matsukawa, Kazunobu Sawamoto
Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration...
January 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28153049/longitudinal-analysis-of-treatment-induced-genomic-alterations-in-gliomas
#20
E Zeynep Erson-Omay, Octavian Henegariu, S Bülent Omay, Akdes Serin Harmancı, Mark W Youngblood, Ketu Mishra-Gorur, Jie Li, Koray Özduman, Geneive Carrión-Grant, Victoria E Clark, Caner Çağlar, Mehmet Bakırcıoğlu, M Necmettin Pamir, Viviane Tabar, Alexander O Vortmeyer, Kaya Bilguvar, Katsuhito Yasuno, Lisa M DeAngelis, Joachim M Baehring, Jennifer Moliterno, Murat Günel
BACKGROUND: Glioblastoma multiforme (GBM) constitutes nearly half of all malignant brain tumors and has a median survival of 15 months. The standard treatment for these lesions includes maximal resection, radiotherapy, and chemotherapy; however, individual tumors display immense variability in their response to these approaches. Genomic techniques such as whole-exome sequencing (WES) provide an opportunity to understand the molecular basis of this variability. METHODS: Here, we report WES-guided treatment of a patient with a primary GBM and two subsequent recurrences, demonstrating the dynamic nature of treatment-induced molecular changes and their implications for clinical decision-making...
February 2, 2017: Genome Medicine
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