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https://www.readbyqxmd.com/read/29782205/nad-repletion-produces-no-therapeutic-effect-in-mice-with-respiratory-chain-complex-iii-deficiency-and-chronic-energy-deprivation
#1
Janne Purhonen, Jayasimman Rajendran, Saara Tegelberg, Olli-Pekka Smolander, Eija Pirinen, Jukka Kallijärvi, Vineta Fellman
Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improve mitochondrial function. We found decreased hepatic NAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed these mice nicotinamide riboside (NR), a NAD+ precursor. A targeted metabolomics verified successful administration and suggested enhanced NAD+ biosynthesis in the treated mice, although hepatic NAD+ concentration was unchanged at the end point...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29781062/antioxidants-in-the-fight-against-atherosclerosis-is-this-a-dead-end
#2
REVIEW
Paola Toledo-Ibelles, Jaime Mas-Oliva
PURPOSE OF REVIEW: The purpose of this review is to focus on the outcome of recent antioxidant interventions using synthetic and naturally occurring molecules established as adjuvant strategies to lipid-lowering or anti-inflammatory therapies designed to reduce the risk of cardiovascular disease. RECENT FINDINGS: To date, accumulated evidence regarding oxidation as a pro-atherogenic factor indicates that redox biochemical events involved in atherogenesis are indeed a very attractive target for the management of cardiovascular disease in the clinic...
May 21, 2018: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29780505/macrophage-mediated-delivery-of-light-activated-nitric-oxide-prodrugs-with-spatial-temporal-and-concentration-control
#3
Michael A Evans, Po-Ju Huang, Yuji Iwamoto, Kelly N Ibsen, Emory M Chan, Yutaka Hitomi, Peter C Ford, Samir Mitragotri
Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+ -doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29779119/a-chemosensitizer-drug-disulfiram-prevents-doxorubicin-induced-cardiac-dysfunction-and-oxidative-stress-in-rats
#4
Varsha K Sonawane, Umesh B Mahajan, Sachin D Shinde, Subhajit Chatterjee, Sandip S Chaudhari, Harshada A Bhangale, Shreesh Ojha, Sameer N Goyal, Chanakya N Kundu, Chandragouda R Patil
In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th day of the initiation of DS treatment. Within 48 h of injection, DOX treatment significantly altered ECG, elevated the ST height, and increased the QT and QRS intervals. It reduced the cardiac levels of injury markers like creatine kinase isoenzyme-MB and lactate dehydrogenase...
May 10, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29778663/glp-1-receptor-agonists-and-reduction-of-cardiometabolic-risk-potential-underlying-mechanisms
#5
REVIEW
Manfredi Rizzo, Dragana Nikolic, Angelo Maria Patti, Carlo Mannina, Giuseppe Montalto, Brooke S McAdams, Ali A Rizvi, Francesco Cosentino
Type 2 diabetes mellitus (T2DM) is a metabolic condition with an elevated impact on cardiovascular (CV) risk. The innovative therapeutic approaches for T2DM - incretin-based therapies (IBTs), including glucagon-like peptide 1 (GLP-1) receptor agonists, have become popular and more widely used in recent years. The available scientific data from clinical studies and clinical practice highlights their beyond glucose-lowering effects, which is achieved without any increase in hypoglycaemia. The former effects include reduction in body weight, lipids, blood pressure, inflammatory markers, oxidative stress, endothelial dysfunction, and subclinical atherosclerosis, thus reducing and potentially preventing CV events...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29778008/plasma-metabolic-changes-in-chinese-hiv-infected-patients-receiving-lopinavir-ritonavir-based-treatment-implications-for-hiv-precision-therapy
#6
Xiaolin Li, Tong Wu, Yongjun Jiang, Zining Zhang, Xiaoxu Han, Wenqing Geng, Haibo Ding, Jing Kang, Qi Wang, Hong Shang
OBJECTIVES: The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. METHODS: 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls...
May 16, 2018: Cytokine
https://www.readbyqxmd.com/read/29777913/the-tp53-induced-glycolysis-and-apoptosis-regulator-mediates-cooperation-between-htlv-1-p30-ii-and-the-retroviral-oncoproteins-tax-and-hbz-and-is-highly-expressed-in-an-in-vivo-xenograft-model-of-htlv-1-induced-lymphoma
#7
Tetiana Hutchison, Aditi Malu, Laçin Yapindi, Rachel Bergeson, Kendra Peck, Megan Romeo, Carolyn Harrod, Jordan Pope, Louisa Smitherman, Wesleigh Gwinn, Lee Ratner, Courtney Yates, Robert Harrod
The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30II induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ...
May 16, 2018: Virology
https://www.readbyqxmd.com/read/29777783/accelerated-lipid-catabolism-and-autophagy-are-cancer-survival-mechanisms-under-inhibited-glutaminolysis
#8
Anna Halama, Michal Kulinski, Shaima S Dib, Shaza B Zaghlool, Kodappully S Siveen, Ahmad Iskandarani, Jonas Zierer, Kirti S Prabhu, Noothan J Satheesh, Aditya M Bhagwat, Shahab Uddin, Gabi Kastenmüller, Olivier Elemento, Steven S Gross, Karsten Suhre
Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777765/in-vitro-and-in-vivo-evaluation-of-an-oral-sustained-release-hepatoprotective-caffeine-loaded-w-o-pickering-emulsion-formula-containing-wheat-germ-oil-and-stabilized-by-magnesium-oxide-nanoparticles
#9
Heba Elmotasem, Hala K Farag, Abeer A A Salama
The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects...
May 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29777706/n-3-polyunsaturated-fatty-acids-ameliorate-hepatic-steatosis-via-the-ppar-%C3%AE-cpt-1%C3%AE-pathway-in-a-mouse-model-of-parenteral-nutrition
#10
Feng Tian, Jiwei Wang, Haifeng Sun, Jianbo Yang, Peng Wang, Songlin Wan, Xuejin Gao, Li Zhang, Jieshou Li, Xinying Wang
Parenteral nutrition (PN) is one of the basic therapies for patients with intestinal failure; however, hepatic steatosis associated with PN limits the long-term use of PN. N-3 polyunsaturated fatty acids (PUFAs) have been used to improve clinical outcomes of patients receiving PN; however, the mechanisms by which n-3 PUFAs ameliorate hepatic steatosis remain unclear. In the present study, C57BL/6J mice were randomly assigned to three treatment groups, namely, enteral nutrition (EN), n-3 PUFAs, and n-6 PUFAs...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777699/cart-peptide-activates-the-nrf2-ho-1-antioxidant-pathway-and-protects-hippocampal-neurons-in-a-rat-model-of-alzheimer-s-disease
#11
Wenyu Jiao, Yongchen Wang, Linghong Kong, Tao Ou-Yang, Qing Meng, Qiang Fu, Zhenzhen Hu
The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777682/inhibition-of-bet-bromodomains-restores-corticosteroid-responsiveness-in-a-mixed-granulocytic-mouse-model-of-asthma
#12
Ahmed Nadeem, Sheikh F Ahmad, Naif O Al-Harbi, Nahid Siddiqui, Khalid E Ibrahim, Sabry M Attia
Asthma is a heterogeneous disease characterized by different endotypes/phenotypes. Th2/Th17 driven mixed granulocytic asthma is one of them and shows resistance to corticosteroid therapy. Bromodomain and extra-terminal (BET) proteins are required for differentiation of Th17 cells which play a pivotal role in neutrophilic inflammation. Therefore, we sought to characterize the differential effects of BET inhibitor versus corticosteroids, and their potential synergism in cockroach allergen extract (CE)-induced mixed granulocytic (eosinophilic and neutrophilic) mouse model of asthma having Th2/Th17 endotype...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29776421/evidence-for-a-hyper-reductive-redox-in-a-sub-set-of-heart-failure-patients
#13
Thiagarajan Sairam, Amit N Patel, Meenu Subrahmanian, Rajendiran Gopalan, Steven M Pogwizd, Sudha Ramalingam, Ramalingam Sankaran, Namakkal Soorapan Rajasekaran
BACKGROUND: Oxidative stress has been linked to heart failure (HF) in humans. Antioxidant-based treatments are often ineffective. Therefore, we hypothesize that some of the HF patients might have a reductive stress (RS) condition. Investigating RS-related mechanisms will aid in personalized optimization of redox homeostasis for better outcomes among HF patients. METHODS: Blood samples were collected from HF patients (n = 54) and healthy controls (n = 42) and serum was immediately preserved in - 80 °C for redox analysis...
May 18, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29774349/role-of-arsenic-3-oxidation-state-methyltransferase-in-arsenic-mediated-apl-treatment-an-in-vitro-investigation
#14
Yasen Maimaitiyiming, Chao Wang, Shi Xu, Khairul Islam, Ye Jia Chen, Chang Yang, Qian Qian Wang, Hua Naranmandura
Arsenic (+3 oxidation state) methyltransferase (AS3MT) is a key enzyme responsible for arsenic metabolism in humans, which facilitates conversion of arsenic trioxide (As2O3) to more reactive metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). However, it is unclear whether the biotransformation of arsenic by AS3MT contributes to the promotion of acute promyelocytic leukemia (APL) therapy. In order to understand the probable role of AS3MT in APL patients, we evaluated the effects of arsenite (iAsIII) and three mixed arsenicals (i...
May 18, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29774098/establishment-of-primary-cell-culture-and-an-intracranial-xenograft-model-of-pediatric-ependymoma-a-prospect-for-therapy-development-and-understanding-of-tumor-biology
#15
Lorena Favaro Pavon, Tatiana Tais Sibov, Silvia Regina Caminada de Toledo, Daniela Mara de Oliveira, Francisco Romero Cabral, Jean Gabriel de Souza, Pamela Boufleur, Luciana C Marti, Jackeline Moraes Malheiros, Edgar Ferreira da Cruz, Fernando F Paiva, Suzana M F Malheiros, Manoel A de Paiva Neto, Alberto Tannús, Sérgio Mascarenhas de Oliveira, Nasjla Saba Silva, Andrea Maria Cappellano, Antonio Sérgio Petrilli, Ana Marisa Chudzinski-Tavassi, Sérgio Cavalheiro
Background: Ependymoma (EPN), the third most common pediatric brain tumor, is a central nervous system (CNS) malignancy originating from the walls of the ventricular system. Surgical resection followed by radiation therapy has been the primary treatment for most pediatric intracranial EPNs. Despite numerous studies into the prognostic value of histological classification, the extent of surgical resection and adjuvant radiotherapy, there have been relatively few studies into the molecular and cellular biology of EPNs...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773191/anti-inflammatory-and-antinociceptive-effects-of-2-2-dipyridyl-diselenide-through-reduction-of-inducible-nitric-oxide-synthase-nuclear-factor-kappa-b-and-c-jun-n-terminal-kinase-phosphorylation-levels-in-the-mouse-spinal-cord
#16
Suzan Gonçalves Rosa, César Augusto Brüning, Ana Paula Pesarico, Ana Cristina Guerra de Souza, Cristina Wayne Nogueira
Appropriate treatment of pain requires analgesics and anti-inflammatory drugs generally associated with undesirable side effects and not fully effective in a significant proportion of patients. Organoselenium compounds elicit a plenty of pharmacological effects in different animal models. Among these compounds, the 2,2`-dipyridyl diselenide (DPD) has a potent antioxidant effect and low toxicity. In this way, the aim of this study was to investigate the possible DPD antinociceptive effect and its mechanism of action, as well as the safety of the compound...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772649/pulmonary-arterial-hypertension-pathophysiology-and-treatment
#17
REVIEW
Norris S H Lan, Benjamin D Massam, Sandeep S Kulkarni, Chim C Lang
Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and subsequent pulmonary arterial pressure, causing right ventricular failure which leads to eventual death if untreated. The management of PAH has advanced rapidly in recent years due to improved understanding of the condition's pathophysiology, specifically the nitric oxide, prostacyclin-thromboxane and endothelin-1 pathways...
May 16, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29772252/sulfiredoxin-1-enhances-cardiac-progenitor-cell-survival-against-oxidative-stress-via-the-upregulation-of-the-erk-nrf2-signal-pathway
#18
Xiuchun Li, Pan He, Xiaoliang Wang, Shuning Zhang, Neil Devejian, Edward Bennett, Chuanxi Cai
Cardiac stem/progenitor cells (CPCs) have recently emerged as a potentially transformative regenerative medicine to repair the infarcted heart. However, the limited survival of donor cells is one of the major challenges for CPC therapy. Our recent research effort on preconditioning human CPCs (hCPCs) with cobalt protoporphyrin (CoPP) indicated that sulfiredoxin-1 (SRXN1) is upregulated upon preconditioning aldehyde dehydrogenase bright hCPCs (ALDHbr -hCPCs) with CoPP. Further studies demonstrated that overexpressing SRXN1 enhanced the survival capacity for ALDHbr -hCPCs...
May 14, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29770166/free-radical-damage-in-ischemia-reperfusion-injury-an-obstacle-in-acute-ischemic-stroke-after-revascularization-therapy
#19
REVIEW
Ming-Shuo Sun, Hang Jin, Xin Sun, Shuo Huang, Fu-Liang Zhang, Zhen-Ni Guo, Yi Yang
Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury) has been found to play a key role in the process...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29770165/targeting-oxidatively-induced-dna-damage-response-in-cancer-opportunities-for-novel-cancer-therapies
#20
REVIEW
Pierpaola Davalli, Gaetano Marverti, Angela Lauriola, Domenico D'Arca
Cancer is a death cause in economically developed countries that results growing also in developing countries. Improved outcome through targeted interventions faces the scarce selectivity of the therapies and the development of resistance to them that compromise the therapeutic effects. Genomic instability is a typical cancer hallmark due to DNA damage by genetic mutations, reactive oxygen and nitrogen species, ionizing radiation, and chemotherapeutic agents. DNA lesions can induce and/or support various diseases, including cancer...
2018: Oxidative Medicine and Cellular Longevity
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