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https://www.readbyqxmd.com/read/29353219/blocking-mitochondrial-cyclophilin-d-ameliorates-tsh-impaired-defensive-barrier-of-artery
#1
Xiaojing Liu, Heng Du, Qiang Chai, Qing Jia, Lu Liu, Meng Zhao, Jun Li, Hui Tang, Wenbin Chen, Lifang Zhao, Li Fang, Ling Gao, Jiajun Zhao
AIMS: Endothelial cells (ECs) constitute the defensive barrier of vasculature, which maintains the vascular homeostasis. Mitochondrial oxidative stress (mitoOS) in ECs significantly affects the initiation and progression of vascular diseases. The higher serum thyroid stimulating hormone (TSH) level is being recognized as a nonconventional risk factor responsible for the increased risk of cardiovascular diseases in subclinical hypothyroidism (SCH). However, effects and underlying mechanisms of elevated TSH on ECs are still ambiguous...
January 9, 2018: Redox Biology
https://www.readbyqxmd.com/read/29352735/s-nitrosated-poly-propylene-sulfide-nanoparticles-for-enhanced-nitric-oxide-delivery-to-lymphatic-tissues
#2
Alex Schudel, Lauren F Sestito, Susan N Thomas
Nitric oxide (NO) is a therapeutic implicated for the treatment of diseases affecting lymphatic tissues, which range from infectious and cardiovascular diseases to cancer. Existing technologies available for NO therapy, however, provide poor bioactivity within lymphatic tissues. In this work, we address this technology gap with a NO encapsulation and delivery strategy leveraging the formation of S-nitrosothiols on lymphatic-targeting Pluronic-stabilized, poly(propylene sulfide)-core nanoparticles (SNO-NP). We evaluated in vivo the lymphatic versus systemic delivery of NO resulting from intradermal administration of SNO-NP benchmarked against a commonly used, commercially available small molecule S-nitrosothiol NO donor, examined signs of toxicity systemically as well as localized to the site of injection, and investigated SNO effects on lymphatic transport and NP uptake by LN-resident cells...
January 20, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#3
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352300/5-aminosalicylic-acid-improves-lipid-profile-in-mice-fed-a-high-fat-cholesterol-diet-through-its-dual-effects-on-intestinal-ppar%C3%AE-and-ppar%C3%AE
#4
Zheng Wang, Debby Koonen, Marten Hofker, Zhijun Bao
Obesity is associated with a series of metabolic complications, including dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent years, intestinal inflammation has been suggested to contribute to obesity related metabolic syndrome and targeting gut inflammation with 5-ASA improves diet induced IR, however, its role in dyslipidemia is unknown and has never been explored. In the present study, we reported for the first time that administration of 5-ASA for 12 weeks significantly improved lipid profile by repressing plasma triglycerides and free cholesterol levels in mice fed high-fat cholesterol diet (HFC)...
2018: PloS One
https://www.readbyqxmd.com/read/29351461/exercise-training-induces-enos-coupling-and-restores-relaxation-in-coronary-arteries-of-heart-failure-rats
#5
Gisele Kruger Couto, Suliana Mesquita Paula, Igor L Gomes-Santos, Carlos Eduardo Negrão, Luciana Venturini Rossoni
Exercise training (ET) has emerged as a non-pharmacological therapy for cardiovascular diseases because of its helpful milieu for improving vascular function. The aim of the present study was to assess whether ET reverses the alterations in vascular reactivity observed in heart failure (HF)-related coronary arteries and to elucidate the molecular mechanisms involved in these adjustments. Male Wistar rats were subjected to either coronary artery ligation or sham operation (SO). Four weeks after the surgery, the rats were divided into two groups: untrained HF (UHF) and exercise-trained HF (THF)...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351446/mechanisms-and-consequences-of-oxidative-stress-in-lung-disease-therapeutic-implications-for-an-aging-populace
#6
Louise Hecker
The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351404/type-2-diabetes-impairs-the-ability-of-skeletal-muscle-pericytes-to-augment-postischemic-neovascularization-in-db-db-mice
#7
Katherine L Hayes, Louis M Messina, Lawrence M Schwartz, Jinglian Yan, Amy S Burnside, Sarah Witkowski
Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective non-interventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild type and type 2 diabetic (T2DM) mice. Wild type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351386/protective-effect-of-c-peptide-on-experimentally-induced-diabetic-nephropathy-and-the-possible-link-between-c-peptide-and-nitric-oxide
#8
Eman A Elbassuoni, Neven M Aziz, Nashwa F El-Tahawy
Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of Nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by NG-nitro-L-arginine methyl ester (L-NAME)...
January 19, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29351198/superoxide-dismutase-mimetic-gc4419-enhances-the-oxidation-of-pharmacological-ascorbate-and-its-anticancer-effects-in-an-h%C3%A2-o%C3%A2-dependent-manner
#9
Collin D Heer, Andrew B Davis, David B Riffe, Brett A Wagner, Kelly C Falls, Bryan G Allen, Garry R Buettner, Robert A Beardsley, Dennis P Riley, Douglas R Spitz
Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH-) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH-, enhancing the anti-tumor effects of AscH- in several cancer types...
January 19, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29350678/pik3r3-regulates-ppar%C3%AE-expression-to-stimulate-fatty-acid-%C3%AE-oxidation-and-decrease-hepatosteatosis
#10
Xi Yang, Yinjia Fu, Fuqing Hu, Xuelai Luo, Junbo Hu, Guihua Wang
Phosphatidylinositol 3-kinase (PI3K) signaling plays an important role in the regulation of cellular lipid metabolism and non-alcoholic fatty liver disease (NAFLD). However, little is known about the role of the regulatory subunits of PI3K in lipid metabolism and NAFLD. In this study, we characterized the functional role of PIK3R3 in fasting-induced hepatic lipid metabolism. In this study, we showed that the overexpression of PIK3R3 promoted hepatic fatty acid oxidation via PIK3R3-induced expression of PPARα, thus improving the fatty liver phenotype in high-fat diet (HFD)-induced mice...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350351/convection-enhanced-delivery-of-cetuximab-conjugated-iron-oxide-nanoparticles-for-treatment-of-spontaneous-canine-intracranial-gliomas
#11
A Courtenay Freeman, Simon R Platt, Shannon Holmes, M Kent, Kelsey Robinson, Elizabeth Howerth, Joe Eagleson, Alexandros Bouras, Milota Kaluzova, Constantinos G Hadjipanayis
Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs for treatment of spontaneously occurring intracranial gliomas in canines after convection-enhanced delivery (CED). The use of CED allowed for direct infusion of the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood brain barrier (BBB) and limiting systemic effects...
January 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29349687/adjunct-and-rescue-therapies-for-refractory-hypoxemia-prone-position-inhaled-nitric-oxide-high-frequency-oscillation-extra-corporeal-life-support
#12
Niall D Ferguson, Claude Guérin
No abstract text is available yet for this article.
January 18, 2018: Intensive Care Medicine
https://www.readbyqxmd.com/read/29349577/combination-therapy-with-sulfasalazine-and-valproic-acid-promotes-human-glioblastoma-cell-death-through-imbalance-of-the-intracellular-oxidative-response
#13
Carlos Gustavo Garcia, Suzana Assad Kahn, Luiz Henrique Medeiros Geraldo, Igor Romano, Ivan Domith, Deborah Christinne Lima E Silva, Fernando Dos Santos Assunção, Marcos José Ferreira, Camila Cabral Portugal, Jorge Marcondes de Souza, Luciana Ferreira Romão, Annibal Duarte Pereira Netto, Flávia Regina Souza Lima, Marcelo Cossenza
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor and still lacks effective therapeutic strategies. It has already been shown that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present antitumoral activities in glioma cell lines. SAS has also been associated with a decrease of intracellular glutathione (GSH) levels through a potent inhibition of xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor capable of activating tumor suppression genes...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29349446/ameliorative-role-of-camel-whey-protein-and-rosuvastatin-on-induced-dyslipidemia-in-mice
#14
Nashwa Ahmed El-Shinnawy, Sahar Sobhy Abd Elhalem, Nawal Zakaria Haggag, Gamal Badr
The incidence of obesity is rapidly increasing throughout the world. Dyslipidemia is a major risk factor for a number of chronic diseases, including diabetes and cardiovascular diseases. This work presents a novel approach to study the activity of camel whey protein (WP) with antioxidant and anti-inflammatory properties as a cheap dietary protein substance extracted from camel milk to produce satiety and help in building muscles. Mice model suffering from dyslipidemia as a result of feeding on high fat-cholesterol diet for 8 weeks were administrated with either camel WP and/or rosuvastatin for 4 weeks...
January 19, 2018: Food & Function
https://www.readbyqxmd.com/read/29348817/a-mitochondrial-targeted-purine-based-hsp90-antagonist-for-leukemia-therapy
#15
Kelly G Bryant, Young Chan Chae, Rogelio L Martinez, John C Gordon, Khaled M Elokely, Andrew V Kossenkov, Steven Grant, Wayne E Childers, Magid Abou-Gharbia, Dario C Altieri
Reprogramming of mitochondrial functions sustains tumor growth and may provide therapeutic opportunities. Here, we targeted the protein folding environment in mitochondria by coupling a purine-based inhibitor of the molecular chaperone Heat Shock Protein-90 (Hsp90), PU-H71 to the mitochondrial-targeting moiety, triphenylphosphonium (TPP). Binding of PU-H71-TPP to ADP-Hsp90, Hsp90 co-chaperone complex or mitochondrial Hsp90 homolog, TRAP1 involved hydrogen bonds, π-π stacking, cation-π contacts and hydrophobic interactions with the surrounding amino acids in the active site...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348439/dual-suppression-of-inner-and-outer-mitochondrial-membrane-functions-augments-apoptotic-responses-to-oncogenic-mapk-inhibition
#16
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348389/efficacy-of-curcumin-as-adjuvant-therapy-to-induce-or-maintain-remission-in-ulcerative-colitis-patients-an-evidence-based-clinical-review
#17
Marcellus Simadibrata, Christopher Christian Halimkesuma, Benedicta Mutiara Suwita
BACKGROUND: treatment guidelines for ulcerative colitis (UC) not yet established. Currently, mesalazine, corticosteroids, and immunomodulators are treatment options for UC. However, they are known to have unpleaseant side effects such as nausea, vomiting, headaches, hepatitis, and male infertility. Curcumin is found in Turmeric plants (Curcuma longa L.), which possesses both anti-inflammatory and antioxidant properties. This study aimed to determine whether curcumin as adjuvant therapy can induce or maintain remission in UC patients...
October 2017: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/29346597/exenatide-increases-il-1ra-concentration-and-induces-nrf-2-keap-1-regulated-anti-oxidant-enzymes-relevance-to-%C3%AE-cell-function
#18
Paresh Dandona, Husam Ghanim, Sanaa Abuaysheh, Kelly Green, Sandeep Dhindsa, Antoine Makdissi, Manav Batra, Nitesh D Kuhadiya, Ajay Chaudhuri
Purpose: We have previously demonstrated anti-inflammatory and antioxidant effects of exenatide. We have now hypothesized that exenatide also increases the plasma concentration of IL-1RA, an endogenous anti-inflammatory protein and modulates the Nrf-2-Keap-1-ARE system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress. Methods: Twenty four obese type 2 diabetic patients on combined oral and insulin therapy were randomized to receive either exenatide 10μg or placebo b...
January 15, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29346320/c-phycocyanin-and-phycocyanobilin-as-remyelination-therapies-for-enhancing-recovery-in-multiple-sclerosis-and-ischemic-stroke-a-preclinical-perspective
#19
REVIEW
Giselle Pentón-Rol, Javier Marín-Prida, Viviana Falcón-Cama
Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery. Here, we show the experimental findings of our group and others supporting the remyelinating effects of C-Phycocyanin (C-PC), the main biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin (PCB), in models of these illnesses...
January 18, 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29345292/preparation-and-characterization-of-the-antibody-recognizing-amacr-inside-its-catalytic-center
#20
Boris V Popov, Gleb I Sutula, Nikolay S Petrov, Ximing J Yang
Alpha-methylacyl-CoA racemase (AMACR) catalyzes the β-oxidation of fatty acids and is overexpressed in carcinomas in various organs, while its inactivation results in the inhibition of cancer growth. In the present study, we prepared and characterized 20 different mouse monoclonal antibodies against human AMACR. In the course of biopanning of a phage peptide commercial library against in-house prepared 6H9 and 2A5, and commercial 13H4 antibodies, 10 phage mimotopes recognized by each type of the antibody were selected...
February 2018: International Journal of Oncology
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