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https://www.readbyqxmd.com/read/28212563/progression-of-motor-deficits-in-glioma-bearing-mice-impact-of-cnf1-therapy-at-symptomatic-stages
#1
Eleonora Vannini, Federica Maltese, Francesco Olimpico, Alessia Fabbri, Mario Costa, Matteo Caleo, Laura Baroncelli
Glioblastoma (GBM) is the most aggressive type of brain tumor. In this context, animal models represent excellent tools for the early detection and longitudinal mapping of neuronal dysfunction, that are critical in the preclinical validation of new therapeutic strategies. In a mouse glioma model, we developed sensitive behavioral readouts that allow early recognizing and following neurological symptoms. We injected GL261 cells into the primary motor cortex of syngenic mice and we used a battery of behavioral tests to longitudinally monitor the dysfunction induced by tumor growth...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212525/ablation-of-ferroptosis-regulator-glutathione-peroxidase-4-in-forebrain-neurons-promotes-cognitive-impairment-and-neurodegeneration
#2
William Sealy Hambright, Rene Solano Fonseca, Liuji Chen, Ren Na, Qitao Ran
Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD); however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus) that are severely afflicted in AD patients might be vulnerable to ferroptosis...
February 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#3
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212522/taking-up-the-cudgels-for-the-traditional-reactive-oxygen-and-nitrogen-species-detection-assays-and-their-use-in-the-cardiovascular-system
#4
REVIEW
Andreas Daiber, Matthias Oelze, Sebastian Steven, Swenja Kröller-Schön, Thomas Münzel
Reactive oxygen and nitrogen species (RONS such as H2O2, nitric oxide) confer redox regulation of essential cellular functions (e.g. differentiation, proliferation, migration, apoptosis), initiate and catalyze adaptive stress responses. In contrast, excessive formation of RONS caused by impaired break-down by cellular antioxidant systems and/or insufficient repair of the resulting oxidative damage of biomolecules may lead to appreciable impairment of cellular function and in the worst case to cell death, organ dysfunction and severe disease phenotypes of the entire organism...
February 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212441/depressive-disorder-and-gastrointestinal-dysfunction-after-myocardial-infarct-are-associated-with-abnormal-tryptophan-5-hydroxytryptamine-metabolism-in-rats
#5
Xiaofang Lu, Yuefen Wang, Chunyan Liu, Yangang Wang
In this study, we investigated the relationship between tryptophan-5-hydroxytryptamine metabolism, depressive disorder, and gastrointestinal dysfunction in rats after myocardial infarction. Our goal was to elucidate the physiopathologic bases of somatic/psychiatric depression symptoms after myocardial infarction. A myocardial infarction model was established by permanent occlusion of the left anterior descending coronary artery. Depression-like behavior was evaluated using the sucrose preference test, open field test, and forced swim test...
2017: PloS One
https://www.readbyqxmd.com/read/28212423/phenolic-extract-from-oleaster-olea-europaea-var-sylvestris-leaves-reduces-colon-cancer-growth-and-induces-caspase-dependent-apoptosis-in-colon-cancer-cells-via-the-mitochondrial-apoptotic-pathway
#6
Wafa Zeriouh, Abdelhafid Nani, Meriem Belarbi, Adélie Dumont, Charlotte de Rosny, Ikram Aboura, Fatima Zahra Ghanemi, Babar Murtaza, Danish Patoli, Charles Thomas, Lionel Apetoh, Cédric Rébé, Dominique Delmas, Naim Akhtar Khan, François Ghiringhelli, Mickael Rialland, Aziz Hichami
Dietary polyphenols, derived from natural products, have received a great interest for their chemopreventive properties against cancer. In this study, we investigated the effects of phenolic extract of the oleaster leaves (PEOL) on tumor growth in mouse model and on cell death in colon cancer cell lines. We assessed the effect of oleaster leaf infusion on HCT116 (human colon cancer cell line) xenograft growth in athymic nude mice. We observed that oleaster leaf polyphenol-rich infusion limited HCT116 tumor growth in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28212375/epilepsy-associated-gene-nedd4-2-mediates-neuronal-activity-and-seizure-susceptibility-through-ampa-receptors
#7
Jiuhe Zhu, Kwan Young Lee, Kathryn A Jewett, Heng-Ye Man, Hee Jung Chung, Nien-Pei Tsai
The neural precursor cell expressed developmentally down-regulated gene 4-2, Nedd4-2, is an epilepsy-associated gene with at least three missense mutations identified in epileptic patients. Nedd4-2 encodes a ubiquitin E3 ligase that has high affinity toward binding and ubiquitinating membrane proteins. It is currently unknown how Nedd4-2 mediates neuronal circuit activity and how its dysfunction leads to seizures or epilepsies. In this study, we provide evidence to show that Nedd4-2 mediates neuronal activity and seizure susceptibility through ubiquitination of GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, (AMPAR)...
February 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28212323/low-intensity-extracorporeal-shock-wave-therapy-enhances-brain-derived-neurotrophic-factor-expression-through-perk-atf4-signaling-pathway
#8
Bohan Wang, Hongxiu Ning, Amanda B Reed-Maldonado, Jun Zhou, Yajun Ruan, Tie Zhou, Hsun Shuan Wang, Byung Seok Oh, Lia Banie, Guiting Lin, Tom F Lue
Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212224/exploring-the-dark-side-of-the-moon-pulmonary-vascular-dysfunction-in-acute-respiratory-distress-syndrome
#9
Michael R Pinsky
No abstract text is available yet for this article.
March 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28212204/1-2-4-dibromophenyl-3-6-6-trimethyl-1-5-6-7-tetrahydro-4h-indazol-4-one-a-novel-opioid-receptor-agonist-with-less-accompanying-gastrointestinal-dysfunction-than-morphine
#10
Po-Kuan Chao, Shau-Hua Ueng, Li-Chin Ou, Teng-Kuang Yeh, Wan-Ting Chang, Hsiao-Fu Chang, Shu-Chun Chen, Pao-Luh Tao, Ping-Yee Law, Horace H Loh, Ming-Fu Cheng, Jian-Ying Chuang, Chiung-Tong Chen, Chuan Shih, Shiu-Hwa Yeh
BACKGROUND: The authors investigated the pharmacology and signaling pathways of the opioid receptors modulated by compound 1, 1-(2,4-dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one. METHODS: In vitro studies of compound 1 were assessed by using a radioligand-binding assay (n = 3), a cyclic adenosine monophosphate assay (n = 3), a β-arrestin assay (n = 3), an internalization assay (n = 3), and an immunohistochemistry (n = 8). In vivo studies of compound 1 were characterized using a tail-flick test (n = 5 to 6), tail-clip test (n = 7), von Frey hair test (n = 5), and charcoal meal test (n = 5)...
February 17, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28212195/suicide-in-guyana-nurses-perspectives
#11
Maureen Anthony, Carla Groh, Jean Gash
Guyana, an English-speaking country on the north coast of South America, has the highest suicide rate in the world. Nurses are an integral part of the healthcare team working with patients experiencing psychological distress and are uniquely qualified to add to the discourse on factors contributing to the high suicide rate in Guyana. The purpose of this study was to explore the attitudes and experiences of nurses and nurse assistants in Guyana related to suicide. Nine registered nurses and nurse assistants who worked at a private hospital in Georgetown, Guyana, were recruited to participate in a focus group...
January 2017: Journal of Forensic Nursing
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#12
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212190/endothelial-cell-disease-emerging-knowledge-from-cerebral-cavernous-malformations
#13
Maria Grazia Lampugnani, Matteo Malinverno, Elisabetta Dejana
PURPOSE OF REVIEW: Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasionally haemorrhagic stroke...
February 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212163/multiple-organ-dysfunction-in-children-mechanically-ventilated-for-acute-respiratory-failure
#14
Scott L Weiss, Lisa A Asaro, Heidi R Flori, Geoffrey L Allen, David Wypij, Martha A Q Curley
OBJECTIVES: The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure. DESIGN: Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013...
February 16, 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28212120/neurogenic-voiding-dysfunction
#15
Petros Georgopoulos, Apostolos Apostolidis
PURPOSE OF REVIEW: This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. RECENT FINDINGS: They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments...
February 16, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28211985/a-girl-with-developmental-delay-ataxia-cranial-nerve-palsies-severe-respiratory-problems-in-infancy-expanding-ndst1-syndrome
#16
Linlea Armstrong, Maja Tarailo-Graovac, Graham Sinclair, Kimberly I Seath, Wyeth W Wasserman, Colin J Ross, Clara D M van Karnebeek
NDST1 encodes an enzyme involved in the first steps in the synthesis of heparan sulfate chains, proteoglycans that are regulators found on the cell surface and in the extracellular matrix. Eight individuals homozygous for one of four family-specific missense mutations in the sulfotransferase domain of the enzyme have been described. They have intellectual disability. Some additionally had hypotonia, ataxia. seizures, and/or short stature, but none had history of respiratory problems. No humans with homozygous null mutations are known...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211970/brain-hemorrhages-in-jacobsen-syndrome-a-retrospective-review-of-six-cases-and-clinical-recommendations
#17
Paul Grossfeld
Jacobsen syndrome is a rare chromosomal disorder caused by distal deletions in the long arm of chromosome 11. All patients with Jacobsen syndrome have Paris-Trousseau syndrome, a bleeding disorder that causes neonatal thrombocytopenia, and persistent platelet dysfunction. Despite that, to date there are no reported cases of hemorrhagic strokes occurring in patients with Jacobsen syndrome. In the last 6 years at least six cases of brain hemorrhages in patients with Jacobsen syndrome have occurred. In this report, we perform a retrospective review of these six cases...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#18
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211883/the-inflammatory-state-provokes-sexual-dimorphism-in-left-ventricular-and-electrocardiographic-effects-of-chronic-cyclosporine-in-rats
#19
Hany M El-Bassossy, Zainy M Banjar, Mahmoud M El-Mas
Although cardiotoxicity has been recognized as an adverse effect of cyclosporine A (CSA), no information exists regarding sex specificity of CSA cardiotoxicity. We tested the hypothesis that left ventricular (LV) and electrocardiographic (ECG) effects of CSA and related inflammatory/histopathological derangements are sex related. CSA reduced the LV slope of end-systolic pressure volume relationship and increased isovolumic relaxation constant. These effects were more pronounced in male compared to female rats, suggesting LV systolic and diastolic dysfunction...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211874/datf4-regulation-of-mitochondrial-folate-mediated-one-carbon-metabolism-is-neuroprotective
#20
Ivana Celardo, Susann Lehmann, Ana C Costa, Samantha Hy Loh, L Miguel Martins
Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity...
February 17, 2017: Cell Death and Differentiation
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