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https://www.readbyqxmd.com/read/29352564/optical-metabolic-imaging-of-irradiated-rat-heart-exposed-to-ischemia-reperfusion-injury
#1
Mette Funding la Cour, Shima Mehrvar, James S Heisner, Mohammad Masoudi Motlagh, Meetha Medhora, Mahsa Ranji, Amadou K S Camara
Whole thoracic irradiation (WTI) is known to cause deterioration in cardiac function. Whether irradiation predisposes the heart to further ischemia and reperfusion (IR) injury is not well known. The aim of this study is to examine the susceptibility of rat hearts to IR injury following a single fraction of 15 Gy WTI and to investigate the role of mitochondrial metabolism in the differential susceptibility to IR injury. After day 35 of irradiation, ex vivo hearts from irradiated and nonirradiated rats (controls) were exposed to 25-min global ischemia followed by 60-min IR, or hearts were perfused without IR for the same protocol duration [time controls (TC)]...
January 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29351465/emerging-potential-benefits-of-modulating-nad-metabolism-in-cardiovascular-disease
#2
Daniel S Matasic, Charles Brenner, Barry London
Nicotinamide adenine dinucleotide (NAD+) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NAD+ is required for the activity of multifunctional enzymes including sirtuins and poly(ADP-ribose) polymerases (PARPs) that regulate post-translational modifications, DNA damage responses, and calcium signaling. Recent research indicates that NAD+ participates in a multitude of processes dysregulated in cardiovascular diseases. Therefore, supplementation of NAD+ precursors including nicotinamide riboside (NR) that boost or replete the NAD+ metabolome may be cardioprotective...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29350405/reactive-oxygen-species-induced-parthanatos-of-immunocytes-by-human-cytomegalovirus-associated-substance
#3
Jung Heon Kim, Jiyeon Kim, Jin Roh, Chan-Sik Park, Ju-Young Seoh, Eung-Soo Hwang
Previous studies examined various immune evasion strategies of human cytomegalovirus (HCMV) to understand HCMV pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, we show that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). We characterized this mechanism of cell death induced by HCMVAIS to understand the death of immunocytes near HCMV-infected lesions...
January 19, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29348808/dual-nampt-hdac-inhibitors-as-a-new-strategy-for-multitargeting-antitumor-drug-discovery
#4
Wei Chen, Guoqiang Dong, Ying Wu, Wannian Zhang, Chaoyu Miao, Chunquan Sheng
Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) inhibitors were designed by a pharmacophore fusion approach. The thiazolocarboxamide inhibitors were highly active for both targets. In particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new strategy for multitarget antitumor drug discovery by simultaneously acting on cancer metabolism and epigenetics.
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29347850/feasibility-of-electrospray-deposition-for-rapid-screening-of-the-cocrystal-formation-and-single-step-continuous-production-of-pharmaceutical-nanococrystals
#5
Shahram Emami, Mohammadreza Siahi-Shadbad, Mohammad Barzegar-Jalali, Khosro Adibkia
OBJECTIVES: This study employed electrospray deposition (ESD) for simultaneous synthesis and particle engineering of cocrystals. SIGNIFICANCE: Exploring new methods for the efficient production of cocrystals with desired particle properties is an essential demand. METHODS: The possibility of cocrystal formation by ESD was examined for indomethacin-saccharin, indomethacin-nicotinamide, naproxen-nicotinamide, and naproxen-iso-nicotinamide cocrystals...
January 18, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29345930/%C3%AE-amino-%C3%AE-carboxymuconate-%C3%AE%C2%B5-semialdehyde-decarboxylase-acmsd-inhibitors-as-novel-modulators-of-de-novo-nicotinamide-adenine-dinucleotide-nad-biosynthesis
#6
Roberto Pellicciari, Paride Liscio, Nicola Giacchè, Francesca De Franco, Andrea Carotti, Janet Robertson, Lucia Cialabrini, Elena Katsyuba, Nadia Raffaelli, Johan Auwerx
NAD+ has a central function in linking cellular metabolism to major cell signaling and gene regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Whilst the beneficial effects of NAD+ boosting are well established in mitochondrial fitness, metabolism, and lifespan, to date, no therapeutic enhancers of de novo NAD+ biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22) the first potent and selective inhibitor of human ACMSD (IC50 = 0...
January 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29344671/role-of-mir-34c-in-the-cognitive-function-of-epileptic-rats-induced-by-pentylenetetrazol
#7
Yiqing Huang, Xixia Liu, Yuhan Liao, Yayun Liao, Donghua Zou, Xing Wei, Qi Huang, Yuan Wu
Studies suggest that microRNA (miR)‑34c may serve a role in cognitive function in rodent and primate groups. A previous study demonstrated an increase in miR‑34c expression in chronic epileptic rats with memory disorders, induced by pentylenetetrazol (PTZ). However, the mechanism underlying the effects of miR‑34c on cognitive function in epileptic rats remains unclear. Therefore, the present study investigated alterations in cognitive function in temporal lobe epileptic rats, induced by repeated injections of PTZ, following treatment with an miR‑34c agomir compared with a scramble group...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344415/rhizoma-coptidis-and-berberine-as-a-natural-drug-to-combat-aging-and-aging-related-diseases-via-anti-oxidation-and-ampk-activation
#8
REVIEW
Zhifang Xu, Wei Feng, Qian Shen, Nannan Yu, Kun Yu, Shenjun Wang, Zhigang Chen, Seiji Shioda, Yi Guo
Aging is the greatest risk factor for human diseases, as it results in cellular growth arrest, impaired tissue function and metabolism, ultimately impacting life span. Two different mechanisms are thought to be primary causes of aging. One is cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK) and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive component of natural Chinese medicine rhizoma coptidis (RC), berberine has recently been reported to expand life span in Drosophila melanogaster, and attenuate premature cellular senescence...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29342889/a-case-control-study-of-the-genetic-variability-in-reactive-oxygen-species-metabolizing-enzymes-in-melanoma-risk
#9
Tze-An Yuan, Vandy Yourk, Ali Farhat, Argyrios Ziogas, Frank L Meyskens, Hoda Anton-Culver, Feng Liu-Smith
Recent studies have shown that ultraviolet (UV)-induced chemiexcitation of melanin fragments leads to DNA damage; and chemiexcitation of melanin fragments requires reactive oxygen species (ROS), as ROS excite an electron in the melanin fragments. In addition, ROS also cause DNA damages on their own. We hypothesized that ROS producing and metabolizing enzymes were major contributors in UV-driven melanomas. In this case-control study of 349 participants, we genotyped 23 prioritized single nucleotide polymorphisms (SNPs) in nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4 (NOX1 and NOX4, respectively), CYBA, RAC1, superoxide dismutases (SOD1, SOD2, and SOD3) and catalase (CAT), and analyzed their associated melanoma risk...
January 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340307/a-patient-with-ckd-develops-cholestatic-liver-injury-during-a%C3%A2-clinical-trial
#10
Emma D A Wagener, Nao Souma, Alexander Hodakowski, Carlos Martinez, Patrick Fox, Rupal Mehta, Matthew J O'Brien, Maureen Bolon, Laura Kulik, Guang-Yu Yang, Tamara Isakova
No abstract text is available yet for this article.
January 2018: KI Reports
https://www.readbyqxmd.com/read/29337590/novel-mechanism-for-nicotinamide-phosphoribosyltransferase-inhibition-of-tnf-%C3%AE-mediated-apoptosis-in-human-lung-endothelial-cells
#11
Radu C Oita, Sara M Camp, Wenli Ma, Ermelinda Ceco, Mark Harbeck, Patrick Singleton, Joe Messana, Xiaoguang Sun, Ting Wang, Joe G N Garcia
Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular (iNAMPT) and extracellular (eNAMPT) proteins. eNAMPT is secreted into the blood and functions as a cytokine/enzyme (cytozyme) that activates NFκB signaling via ligation of the TLR4 receptor, further serving as a biomarker for inflammatory lung disorders such as the acute respiratory distress syndrome (ARDS). In contrast, iNAMPT is involved in nicotinamide mononucleotide (NMN) synthesis and has been implicated in the regulation of cellular apoptosis, although the exact mechanisms for this regulation are poorly understood...
January 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29332790/ultrasensitive-electrochemical-detection-of-poly-adp-ribose-polymerase-1-via-polyaniline-deposition
#12
Yong Liu, Jiahui Fan, Li Shangguan, Yuanjian Liu, Yuanqing Wei, Wei Wei, Songqin Liu
Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target because it is closely related to the development of tumor. So, studies on its detection and inhibitors evaluation have attracted more attention. It is interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the existence of nicotinamide adenine dinucleotide (NAD+), possess twice charge density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and multiple branched strands...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29330215/mir-195-regulates-metabolism-in-failing-myocardium-via-alterations-in-sirt3-expression-and-mitochondrial-protein-acetylation
#13
Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Estibaliz Castillero, Peter J Kennel, Danielle L Brunjes, Marcus Franz, Sven Möbius-Winkler, Konstantinos Drosatos, Isaac George, Emily I Chen, Paolo C Colombo, P Christian Schulze
Background -Heart failure (HF) leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. Interestingly, unique cardiac and systemic miRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium...
January 12, 2018: Circulation
https://www.readbyqxmd.com/read/29330025/the-role-of-extracellular-and-intracellular-nicotinamide-phosphoribosyl-transferase-in-cancer-diagnostic-and-therapeutic-perspectives-and-challenges
#14
REVIEW
Maria Dalamaga, Gerasimos Socrates Christodoulatos, Christos S Mantzoros
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties...
January 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29329924/effects-of-dark-chocolate-on-endothelial-function-in-patients-with-non-alcoholic-steatohepatitis
#15
L Loffredo, F Baratta, P Ludovica, S Battaglia, R Carnevale, C Nocella, M Novo, G Pannitteri, F Ceci, F Angelico, F Violi, M Del Ben
BACKGROUND AND AIM: Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH...
November 13, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29329393/tgf-%C3%AE-mediated-nadph-oxidase-4-dependent-oxidative-stress-promotes-colistin-induced-acute-kidney-injury
#16
Bo Young Jeong, Se-Ra Park, Sungkwon Cho, Seong-Lan Yu, Hoi Young Lee, Chang Gyo Park, Jaeku Kang, Da-Young Jung, Moon Hyang Park, Won-Min Hwang, Sung-Ro Yun, Ju-Young Jung, Se-Hee Yoon
Background: Colistin (polymyxin E) is an important constituent of the polymyxin class of cationic polypeptide antibiotics. Intrarenal oxidative stress can contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide 3-phosphate oxidases (Noxs) are important sources of reactive oxygen species. Among the various types of Noxs, Nox4 is predominantly expressed in the kidney. Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in colistin-induced acute kidney injury using in vivo and in vitro models...
January 9, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29329317/oxidative-stress-caused-by-activation-of-nadph-oxidase-4-promotes-contrast-induced-acute-kidney-injury
#17
Bo Young Jeong, Hoi Young Lee, Chang Gyo Park, Jaeku Kang, Seong-Lan Yu, Du-Ri Choi, Seung-Yun Han, Moon Hyang Park, Sungkwon Cho, Soo Young Lee, Won-Min Hwang, Sung-Ro Yun, Hye-Myung Ryu, Eun-Joo Oh, Sun-Hee Park, Yong-Lim Kim, Se-Hee Yoon
Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831)...
2018: PloS One
https://www.readbyqxmd.com/read/29329057/chronic-corticosterone-induced-depression-mediates-premature-aging-in-rats
#18
Xiaoxian Xie, Qichen Shen, Lingyan Ma, Yangyang Chen, Binggong Zhao, Zhengwei Fu
BACKGROUND: Stress hormones such as corticosterone (CORT) play an essential role in the development of depression. Chronic CORT administration has been shown to induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to depression, which was in turn associated with accelerated aging. However, the effect of CORT administration on aging remains unclear. METHODS: Rats were acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n = 10 each) for 21 consecutive days...
January 2, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29327278/nicotinamide-inhibits-ethanol-induced-caspase-3-and-parp-1-over-activation-and-subsequent-neurodegeneration-in-the-developing-mouse-cerebellum
#19
Alessandro Ieraci, Daniel G Herrera
Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable...
January 11, 2018: Cerebellum
https://www.readbyqxmd.com/read/29327228/postoperative-intermittent-fasting-prevents-hippocampal-oxidative-stress-and-memory-deficits-in-a-rat-model-of-chronic-cerebral-hypoperfusion
#20
Yuan Hu, Miao Zhang, Yunyun Chen, Ying Yang, Jun-Jian Zhang
PURPOSE: Whether intermittent fasting (IF) treatment after stroke can prevent its long-term detrimental effects remains unknown. Here, we investigate the effects of postoperative IF on cognitive deficits and its underlying mechanisms in a permanent two-vessel occlusion (2VO) vascular dementia rat model. METHODS: Rats were subjected to either IF or ad libitum feeding 1 week after 2VO surgery. The cognition of rats was assessed using the novel object recognition (NOR) task and Morris water maze (MWM) 8 weeks after surgery...
January 11, 2018: European Journal of Nutrition
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