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https://www.readbyqxmd.com/read/29156675/glioblastoma-and-glioblastoma-stem-cells-are-dependent-on-functional-mth1
#1
Linda Pudelko, Pegah Rouhi, Kumar Sanjiv, Helge Gad, Christina Kalderén, Andreas Höglund, Massimo Squatrito, Alberto J Schuhmacher, Steven Edwards, Daniel Hägerstrand, Ulrika Warpman Berglund, Thomas Helleday, Lars Bräutigam
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156153/hyperbaric-oxygen-therapy-is-not-associated-with-oxidative-stress-assessed-using-plasma-f2-isoprostanes-and-isofurans
#2
Tomas Corcoran, Sonya Ting, Emilie Mas, Michael Phillips, Edmond O'Loughlin, Anne Barden, Trevor A Mori
BACKGROUND AND AIMS: Hyperbaric oxygen (HBO) therapy is increasingly used in medical practice as a means of enhancing the formation of collagen matrix and angiogenesis, thus promoting healing in wounds and necrotic tissue. However, there are concerns that oxygen can also associate with increased production of oxygen free radicals and oxidative stress. F2-Isoprostanes (F2-IsoPs) formed by non-enzymatic oxidation of arachidonic acid (AA) are reliable measures for assessing oxidative stress in vivo...
December 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29155815/allopurinol-attenuates-acute-kidney-injury-following-bothrops-jararaca-envenomation
#3
Pedro Henrique França Gois, Monique Silva Martines, Daniela Ferreira, Rildo Volpini, Daniele Canale, Ceila Malaque, Renato Crajoinas, Adriana Castello Costa Girardi, Maria Heloisa Massola Shimizu, Antonio Carlos Seguro
Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI...
November 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29155560/asymmetric-assembling-of-iron-oxide-nanocubes-for-improving-magnetic-hyperthermia-performance
#4
Dina Niculaes, Aidin Lak, George C Anyfantis, Sergio Marras, Oliver Laslett, Sahitya K Avugadda, Marco Cassani, David Serantes, Ondrej Hovorka, Roy Chantrell, Teresa Pellegrino
agnetic hyperthermia (MH) based on magnetic nanoparticles (MNPs) is a promising adjuvant therapy for cancer treatment. Particle clustering leading to complex magnetic interactions affects the heat generated by MNPs during MH. The heat efficiencies, theoretically predicted, are still poorly understood because of lack of the control of the fabrication of such clusters with defined geometries and thus their functionality. This study aims to correlate the heating efficiency under MH of individually coated iron oxide nanocubes (IONCs) vs...
November 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/29155496/insulin-resistance-in-chronic-kidney-disease
#5
REVIEW
Hong Xu, Juan J Carrero
This review provides an overview of insulin resistance (IR) in patients with chronic kidney disease (CKD). IR is a pathological state in which target tissues fail to respond normally to insulin. IR is understood as a consequence of CKD and its prevalence rises particularly in advanced CKD stages. Mechanisms leading to IR are complex and multifactorial, involving post-receptor signaling defects, unhealthy lifestyles, metabolic acidosis, inflammation, oxidative stress, vitamin D deficiency, anemia, and uremic toxicity, as shown by human and experimental studies over the last 30 years...
December 2017: Nephrology
https://www.readbyqxmd.com/read/29155491/variation-in-the-response-of-clozapine-biotransformation-pathways-in-human-hepatic-microsomes-to-cyp1a2-and-cyp3a4-selective-inhibitors
#6
Michael Murray, Wei V Zhang, Robert J Edwards
The atypical antipsychotic agent clozapine (CLZ) is effective in many patients who are resistant to conventional antipsychotic drugs. Cytochromes P450 (CYPs) 1A2 and 3A4 oxidise CLZ to norCLZ and CLZ N-oxide in human liver. Concurrent treatment with inducers and inhibitors of CYP1A2 modulates CLZ elimination that disrupts therapy. Drug-drug interactions involving CYP3A4 are also significant but less predictable. To further characterise the factors underlying these interactions, we used samples from a cohort of human livers to assess variation in CLZ oxidation pathways in relation to intrinsic CYP3A4 and CYP1A2 activities and the effects of the corresponding selective inhibitors ketoconazole (0...
November 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29155449/baicalein-inhibits-acinar-to-ductal-metaplasia-of-pancreatic-acinal-cell-ar42j-via-improving-the-inflammatory-microenvironment
#7
Wei-Ling Pu, Ying-Ying Luo, Ru-Yu Bai, Ao-Wei Guo, Kun Zhou, Yun-Sha Zhang, Lin Miao, Curzio Rüegg, Micheal O Hottiger, Xiu-Mei Gao, Li-Kang Sun
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29155409/biomaterial-strategies-for-limiting-the-impact-of-secondary-events-following-spinal-cord-injury
#8
Trevor R Ham, Nic D Leipzig
The nature of traumatic spinal cord injury (SCI) often involves limited recovery and long-term quality of life complications. The initial injury sets off a variety of secondary cascades, which result in an expanded lesion area. Ultimately, the native tissue fails to regenerate. As treatments are developed in the laboratory, the management of this secondary cascade is an important first step in achieving recovery of normal function. Current literature identifies four broad targets for intervention: inflammation, oxidative stress, disruption of the blood-spinal cord barrier, and formation of an inhibitory glial scar...
November 20, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/29155336/evaluation-of-the-combined-effect-of-nir-laser-and-ionizing-radiation-on-cellular-damages-induced-by-iudr-loaded-plga-coated-nano-graphene-oxide
#9
Samira Kargar, Samideh Khoei, Sepideh Khoee, Sakine Shirvalilou, Seied Rabi Mahdavi
Glioma is one of the most common malignant cancers of the central nervous system (CNS). Radiatherapy and chemotherapy may be used to slow the growth of tumors that cannot be removed with surgery. The current study developed a combination therapy tool using Nanographene oxide (NGO) functionalized with poly lactic-co-glycolic acid (PLGA) as a carrier of 5-iodo-2-deoxyuridine (IUdR) for glioma cancer treatment. U87MG cells were treated in different groups with IUdR, PLGA-coated Nanographene oxide (PLGA-NGO), IUdR-loaded PLGA-coated Nanographene oxide (IUdR-PLGA-NGO), 2Gy 6MV X-ray radiation, and near-infrared region (NIR) laser radiation...
November 16, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29154977/polymer-nitric-oxide-donors-potentiate-the-treatment-of-experimental-solid-tumours-by-increasing-drug-accumulation-in-the-tumour-tissue
#10
M Studenovsky, L Sivak, O Sedlacek, R Konefal, V Horkova, T Etrych, M Kovar, B Rihova, M Sirova
The delivery of nitric oxide (NO) specifically to solid tumours was explored in this study as a strategy to augment the passive accumulation of nanomedicines in tumours induced by the Enhanced Permeability and Retention (EPR) effect. An increase in accumulation was achieved by the binding of the chemical precursor of NO, based on an organic nitrate, to a water-soluble synthetic polymer drug carrier. Four structurally different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer NO donors were synthesized...
November 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29154687/pyruvate-enhancement-of-cardiac-performance-cellular-mechanisms-and-clinical-application
#11
Robert T Mallet, Albert H Olivencia-Yurvati, Rolf Bünger
Cardiac contractile function is adenosine-5'-triphosphate (ATP)-intensive, and the myocardium's high demand for oxygen and energy substrates leaves it acutely vulnerable to interruptions in its blood supply. The myriad cardioprotective properties of the natural intermediary metabolite pyruvate make it a potentially powerful intervention against the complex injury cascade ignited by myocardial ischemia-reperfusion. A readily oxidized metabolic substrate, pyruvate augments myocardial free energy of ATP hydrolysis to a greater extent than the physiological fuels glucose, lactate and fatty acids, particularly when it is provided at supra-physiological plasma concentrations...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29154501/challenges-to-laser-assisted-drug-delivery-applying-theory-to-clinical-practice
#12
Omer Ibrahim, Emily Wenande, Sara Hogan, Kenneth A Arndt, Merete Haedersdal, Jeffrey S Dover
BACKGROUND: The percutaneous penetration of topically applied compounds can be enhanced using external chemical or physical sources and thus laser-assisted drug delivery is a burgeoning area of interest within the field of dermatology. OBJECTIVES: This article briefly discusses the mechanism of laser-assisted drug delivery and expands upon the challenges and safety issues that may arise in the clinical implementation of this modality. RESULTS: The existing literature demonstrates that investigators and clinicians in dermatology have successfully delivered anti-inflammatory, anti-neoplastic, and anti-oxidative medications transdermally for the treatment of a variety of conditions including scarring, photoageing, and cutaneous neoplasia...
November 20, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29154270/ubisol-q10-a-nanomicellar-water-soluble-formulation-of-coq10-treatment-inhibits-alzheimer-type-behavioral-and-pathological-symptoms-in-a-double-transgenic%C3%A2-mouse%C3%A2-tgapeswe-%C3%A2-psen1de9-model-of-alzheimer-s-disease
#13
Krithika Muthukumaran, Annie Kanwar, Caleb Vegh, Alexandra Marginean, Austin Elliott, Nicholas Guilbeault, Alexander Badour, Marianna Sikorska, Jerome Cohen, Siyaram Pandey
 Alzheimer's disease (AD) is one of the most common neurodegenerative pathologies for which there are no effective therapies to halt disease progression. Given the increase in the incidence of this disorder, there is an urgent need for pharmacological intervention. Unfortunately, recent clinical trials produced disappointing results. Molecular mechanisms of AD are converging on the notion that mitochondrial dysfunction, oxidative stress, and accumulation of dysfunctional proteins are involved in AD pathology...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154063/the-impact-of-silymarin-on-antioxidant-and-oxidative-status-in-patients-with-%C3%AE-thalassemia-major-a-crossover-randomized-controlled-trial
#14
Hadi Darvishi-Khezri, Ebrahim Salehifar, Mehrnoush Kosaryan, Hossein Karami, Abbas Alipour, Fatemeh Shaki, Aily Aliasgharian
BACKGROUND & AIMS: Blood transfusion therapy is lifesaving for individuals with β-thalassemia major (β-TM). Iron burden following blood transfusion is the main cause of oxidative stress (OS) and organ dysfunction in these patients. The aim of this study was to evaluate the effects of silymarin on serum antioxidant and oxidative status in patients with β-TM. METHODS: A crossover, randomized controlled trial was performed on 82 thalassemia patients. In two periods of 12 weeks, patients received 420mg silymarin (divided into three equal 140-mg daily doses) and placebo...
December 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/29153989/psen1-mutant-ipsc-derived-model-reveals-severe-astrocyte-pathology-in-alzheimer-s-disease
#15
Minna Oksanen, Andrew J Petersen, Nikolay Naumenko, Katja Puttonen, Šárka Lehtonen, Max Gubert Olivé, Anastasia Shakirzyanova, Stina Leskelä, Timo Sarajärvi, Matti Viitanen, Juha O Rinne, Mikko Hiltunen, Annakaisa Haapasalo, Rashid Giniatullin, Pasi Tavi, Su-Chun Zhang, Katja M Kanninen, Riikka H Hämäläinen, Jari Koistinaho
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls...
November 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153923/macrophages-sensing-oxidized-damps-reprogram-their-metabolism-to-support-redox-homeostasis-and-inflammation-through-a-tlr2-syk-ceramide-dependent-mechanism
#16
Vlad Serbulea, Clint M Upchurch, Katelyn W Ahern, Gael Bories, Paxton Voigt, Dory E DeWeese, Akshaya K Meher, Thurl E Harris, Norbert Leitinger
OBJECTIVE: Macrophages control tissue homeostasis and inflammation by sensing and responding to environmental cues. However, the metabolic adaptation of macrophages to oxidative tissue damage and its translation into inflammatory mechanisms remains enigmatic. METHODS: Here we identify the critical regulatory pathways that are induced by endogenous oxidation-derived DAMPs (oxidized phospholipids, OxPL) in vitro, leading to formation of a unique redox-regulatory metabolic phenotype (Mox), which is strikingly different from conventional classical or alternative macrophage activation...
November 7, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29153608/cofilin-signaling-in-hemin-induced-microglial-activation-and-inflammation
#17
Muhammad Shahdaat Bin Sayeed, Qasim Alhadidi, Zahoor A Shah
Intracerebral hemorrhage (ICH) is the most severe form of stroke and is further exacerbated by the secondary injury involving inflammatory response due to the activation of microglia. This secondary injury is partly due to the toxic effects of hemin, an endogenous breakdown product of hemoglobin. Cofilin, an actin depolymerizing factor, controls actin dynamics and has been previously shown to be involved in mediating neuronal cell death in ischemic conditions and during bacterial lipopolysaccharide induced microglial activation...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29152647/cryptotanshinone-exhibits-therapeutical-effects-on-cerebral-stroke-through-the-pi3k-akt%C3%A2-enos-signaling-pathway
#18
Weixin Zhu, Weihong Qiu, Ailan Lu
Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS)...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29152258/in-vitro-screening-of-neuroprotective-activity-of-indian-medicinal-plant-withania-somnifera
#19
Manjeet Singh, Charles Ramassamy
Canine cognitive dysfunction (CCD) is an age-dependent neurodegenerative condition characterised by changes in decline in learning and memory patterns. The neurodegenerative features of CCD in ageing dogs and cats are similar to human ageing and Alzheimer's disease (AD). Discovering neuroprotective disease-modifying therapies against CCD and AD is a major challenge. Strong evidence supports the role of amyloid β peptide deposition and oxidative stress in the pathophysiology of CCD and AD. In both the human and canine brain, oxidative damage progressively increases with age...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29152215/ozone-therapy-an-overview-of-pharmacodynamics-current-research-and-clinical-utility
#20
REVIEW
Noel L Smith, Anthony L Wilson, Jason Gandhi, Sohrab Vatsia, Sardar Ali Khan
The use of ozone (O3) gas as a therapy in alternative medicine has attracted skepticism due to its unstable molecular structure. However, copious volumes of research have provided evidence that O3's dynamic resonance structures facilitate physiological interactions useful in treating a myriad of pathologies. Specifically, O3 therapy induces moderate oxidative stress when interacting with lipids. This interaction increases endogenous production of antioxidants, local perfusion, and oxygen delivery, as well as enhances immune responses...
July 2017: Medical Gas Research
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