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https://www.readbyqxmd.com/read/29752600/pancreatic-cancer-metabolism-molecular-mechanisms-and-clinical-applications
#1
REVIEW
Abdel Nasser Hosein, Muhammad Shaalan Beg
PURPOSE OF REVIEW: Pancreatic adenocarcinoma is a leading cause of cancer mortality in western countries with a uniformly poor prognosis. Unfortunately, there has been little in the way of novel therapeutics for this malignancy over the last several decades. Derangements in metabolic circuitry favoring excess glycolysis are increasingly recognized as a key hallmark of cancer. RECENT FINDINGS: The role of alterations in glutamine metabolism in pancreatic tumor progression has been elucidated in animal models and human cells lines, and there has been considerable interest in exploiting these aberrations for the treatment of pancreatic cancer...
May 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29750296/hyperoside-protects-human-kidney%C3%A2-2-cells-against-oxidative-damage-induced-by-oxalic-acid
#2
Yongliang Chen, Lihong Ye, Wangjian Li, Dongzhang Li, Feng Li
The majority of renal calculi (kidney stones) are calcium stones. Oxidative damage to renal tubular epithelial cells induced by reactive oxygen species (ROS) is the predominant cause of calcium oxalate stone formation. Hyperoside (Hyp) is a flavonol glycoside extracted from medicinal plants and appears to exhibit potent antioxidant activity in various cells. The aim of the present study was to investigate the protective effect of Hyp on renal cells exposed to oxidative stress simulated by oxalic acid (OA), and to determine whether the underlying mechanism involves the nuclear factor E2‑related factor2 (Nrf2)‑antioxidative response element signaling pathway...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29746824/reduction-of-2-methoxy-1-4-naphtoquinone-by-mitochondrially-localized-nqo1-yielding-nad-supports-substrate-level-phosphorylation-during-respiratory-inhibition
#3
Dora Ravasz, Gergely Kacso, Viktoria Fodor, Kata Horvath, Vera Adam-Vizi, Christos Chinopoulos
Provision of NAD+ for oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA by the ketoglutarate dehydrogenase complex (KGDHC) is critical for maintained operation of succinyl-CoA ligase yielding high-energy phosphates, a process known as mitochondrial substrate-level phosphorylation (mSLP). We have shown previously that when NADH oxidation by complex I is inhibited by rotenone or anoxia, mitochondrial diaphorases yield NAD+ , provided that suitable quinones are present (Kiss G et al., FASEB J 2014, 28:1682)...
May 7, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29743984/ingredients-from-litsea-garrettii-as-potential-preventive-agents-against-oxidative-insult-and-inflammatory-response
#4
Yan-Ru Li, Guo-Hui Li, Lin Sun, Lin Li, Yue Liu, De-Gang Kong, Shu-Qi Wang, Dong-Mei Ren, Xiao-Ning Wang, Hong-Xiang Lou, Tao Shen
Oxidative stress and inflammation undoubtedly contribute to the pathogenesis of many human diseases. The nuclear transcription factor erythroid 2-related factor (Nrf2) and the nuclear factor κ B (NF- κ B) play central roles in regulation of oxidative stress and inflammation and thus are targets for developing agents against oxidative stress- and inflammation-related diseases. Our previous study indicated that the EtOH extract of Litsea garrettii protected human bronchial epithelial cells against oxidative insult via the activation of Nrf2...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29742868/modulated-gene-expression-of-toxoplasma-gondii-infected-retinal-pigment-epithelial-cell-line-arpe-19-via-pi3k-akt-or-mtor-signal-pathway
#5
Wei Zhou, Juan-Hua Quan, Fei-Fei Gao, Hassan Ahmed Hassan Ahmed Ismail, Young-Ha Lee, Guang-Ho Cha
Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes...
April 2018: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/29733330/benefits-of-caloric-restriction-in-longevity-and-chemical-induced-tumorigenesis-are-transmitted-independent-of-nqo1
#6
Alberto Diaz-Ruiz, Andrea Di Francesco, Bethany A Carboneau, Sophia R Levan, Kevin J Pearson, Nathan L Price, Theresa M Ward, Michel Bernier, Rafael de Cabo, Evi M Mercken
Caloric restriction (CR) is the most potent nonpharmacological intervention known to both protect against carcinogenesis and delay aging in laboratory animals. There is a growing number of anticarcinogens and CR mimetics that activate NAD(P)H:quinone oxidoreductase 1 (NQO1). We have previously shown that NQO1, an antioxidant enzyme that acts as an energy sensor through modulation of intracellular redox and metabolic state, is upregulated by CR. Here, we used NQO1-knockout (KO) mice to investigate the role of NQO1 in both the aging process and tumor susceptibility, specifically in the context of CR...
May 4, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29725495/characterization-of-the-antioxidant-effects-of-%C3%AE-oryzanol-involvement-of-the-nrf2-pathway
#7
W Rungratanawanich, G Abate, M M Serafini, M Guarienti, M Catanzaro, M Marziano, M Memo, C Lanni, D Uberti
γ -Oryzanol (ORY) is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS) scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293). The 24 h ORY exposure significantly prevented hydrogen peroxide- (H2 O2 -) induced ROS/RNS production at 3 h, and this effect was sustained for at least 24 h...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29712428/nad-p-h-quinone-oxidoreductase-1-nqo1-as-a-therapeutic-and-diagnostic-target-in-cancer
#8
Kuojun Zhang, Dong Cheng, Kun Ma, Xiaoxing Wu, Haiping Hao, Sheng Jiang
NAD(P)H: quinone oxidoreductase 1 (NQO1) is a two-electron reductase responsible for detoxification of quinones and also bioactivation of certain quinones. It is abnormally overexpressed in many tumors and intimately linked with multiple carcinogenic processes. NQO1 is considered to be a cancer-specific target for therapy but currently available NQO1 inhibitors have not yet led to chemotherapeutic success. Utilization of NOQ1's ability to bioactivate chemotherapeutic quinones however has emerged as a promising selective anticancer therapy...
April 30, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29706024/overexpression-of-cyb5r3-and-nqo1-two-nad-producing-enzymes-mimics-aspects-of-caloric-restriction
#9
Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A Aon, Kenneth W Fishbein, Kevin J Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael de Cabo
Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases...
April 28, 2018: Aging Cell
https://www.readbyqxmd.com/read/29697282/the-role-of-genetic-variants-in-the-association-between-dietary-acrylamide-and-advanced-prostate-cancer-in-the-netherlands-cohort-study-on-diet-and-cancer
#10
Andy Perloy, Leo J Schouten, Piet A van den Brandt, Roger Godschalk, Frederik-Jan van Schooten, Janneke G F Hogervorst
To investigate the association between dietary acrylanide and advanced prostate cancer, we examined acrylamide-gene interactions for advanced prostate cancer risk by using data from the Netherlands Cohort Study. Participants (n = 58,279 men) completed a baseline food frequency questionnaire (FFQ), from which daily acrylamide intake was calculated. At baseline, 2,411 men were randomly selected from the full cohort for case-cohort analysis. Fifty eight selected single nucleotide polymorphisms (SNPs) and two gene deletions in genes in acrylamide metabolism, DNA repair, sex steroid systems, and oxidative stress were analyzed...
April 26, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29680643/phosphorylation-of-nuclear-factor-erythroid-2-like-2-nfe2l2-in-mammary-tissue-of-holstein-cows-during-the-periparturient-period-is-associated-with-mrna-abundance-of-antioxidant-gene-networks
#11
L Q Han, Z Zhou, Y Ma, F Batistel, J S Osorio, J J Loor
Changes in the production of reactive oxygen species in the mammary gland of dairy cows during the periparturient period could lead to oxidative stress and potentially impair mammary function. Phosphorylation of the transcription factor nuclear factor erythroid 2-like 2 (NFE2L2), also known as nuclear factor-E2-related factor 2, controls mRNA abundance of genes encoding antioxidant proteins and enzymes. The hypothesis was that NFE2L2 phosphorylation status and target gene mRNA abundance in the mammary gland of dairy cows is altered around parturition...
April 18, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29659176/nrf2-attenuates-inflammatory-response-in-copd-emphysema-crosstalk-with-wnt3a-%C3%AE-catenin-and-ampk-pathways
#12
Wenhui Cui, Zhihui Zhang, Panpan Zhang, Jiao Qu, Cheng Zheng, Xiaoting Mo, Wencheng Zhou, Liang Xu, Hongwei Yao, Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway...
April 16, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29652514/-nqo1-gene-c609t-polymorphism-dbsnp-rs1800566-and-digestive-tract-cancer-risk-a-meta-analysis
#13
Upendra Yadav, Pradeep Kumar, Vandana Rai
Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H): quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Authors conducted a meta-analysis to investigate association between C609T polymorphism and DT cancer risk. Eligible studies were extracted from the databases of PubMed, Google Scholar, Science Direct, and Springer Link. All retrieved articles were evaluated. All statistical analyses were performed using Open Meta-Analyst and MIX1...
April 13, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29642608/neuroprotective-effects-of-four-phenylethanoid-glycosides-on-h%C3%A2-o%C3%A2-induced-apoptosis-on-pc12-cells-via-the-nrf2-are-pathway
#14
Maiquan Li, Tao Xu, Fei Zhou, Mengmeng Wang, Huaxin Song, Xing Xiao, Baiyi Lu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H₂O₂-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM)...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29626606/curcumin-provides-neuroprotection-in-models-of-traumatic-brain-injury-via-the-nrf2-are-signaling-pathway
#15
Wei Dai, Handong Wang, Jiang Fang, Yihao Zhu, Jian Zhou, Xiaoliang Wang, Yuan Zhou, Mengliang Zhou
Curcumin has been found to play the protective role in many neurological disorders, however, its roles and the underlying molecular mechanisms in traumatic brain injury (TBI) are not fully understood. The aim of this study was to investigate the potential neuroprotection of curcumin and the possible role of Nrf2-ARE pathway in the weight-drop model of TBI. The administration of curcumin significantly ameliorated secondary brain injury induced by TBI, such as brain water content, oxidative stress, neurological severity score, and neuronal apoptosis...
April 4, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29621903/impact-of-nrf2-on-tumor-growth-and-drug-sensitivity-in-oncogenic-k-ras-transformed-cells-in-vitro-and-in-vivo
#16
Jiajia Shao, Christophe Glorieux, Jianwei Liao, Ping Chen, Wenhua Lu, Zhenhao Liang, Shijun Wen, Yumin Hu, Peng Huang
K-ras is one of the most common oncogenes in human cancers, and its aberrant activation may lead to malignant transformation associated with oxidative stress and activation of the transcription factor Nrf2 that regulates multiple detoxification enzymes. The purpose of this research was to use gene editing technology to evaluate the role of Nrf2 in affecting tumor growth and drug sensitivity of K-rasG12V -transformed cells. We showed that induction of K-rasG12V caused a significant activation of Nrf2 associated with increased expression of its target genes NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1)...
April 5, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29621130/astaxanthin-promotes-nrf2-are-signaling-to-inhibit-hg-induced-renal-fibrosis-in-gmcs
#17
Xi Xie, Qing Chen, Jun Tao
Oxidative stress is the main cause of diabetic nephropathy (DN) progression. Nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling is a crucial cellular defense system to cope with oxidative stress. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid with remarkable antioxidative capacity. AST exerted renal protective in diabetic rats. This study aimed to determine whether AST could alleviate the pathological progress of DN by activating Nrf2/ARE signaling and diminishing the excessive oxidative stress and fibronectin (FN) accumulation in glomerular mesangial cells (GMCs) challenged with high glucose (HG)...
April 5, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29615906/mechanisms-of-triptolide-induced-hepatotoxicity-and-protective-effect-of-combined-use-of-isoliquiritigenin-possible-roles-of-nrf2-and-hepatic-transporters
#18
Zhenyan Hou, Lei Chen, Pingfei Fang, Hualin Cai, Huaibo Tang, Yongbo Peng, Yang Deng, Lingjuan Cao, Huande Li, Bikui Zhang, Miao Yan
Triptolide (TP), the main bioactive component of Tripterygium wilfordii Hook F, can cause severe hepatotoxicity. Isoliquiritigenin (ISL) has been reported to be able to protect against TP-induced liver injury, but the mechanisms are not fully elucidated. This study aims to explore the role of nuclear transcription factor E2-related factor 2 (Nrf2) and hepatic transporters in TP-induced hepatotoxicity and the reversal protective effect of ISL. TP treatment caused both cytotoxicity in L02 hepatocytes and acute liver injury in mice...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29571471/persimmon-vinegar-polyphenols-protect-against-hydrogen-peroxide-induced-cellular-oxidative-stress-via-nrf2-signalling-pathway
#19
Bo Zou, Gengsheng Xiao, Yujuan Xu, Jijun Wu, Yuanshan Yu, Manqin Fu
Since polyphenols are known to exhibit antioxidative properties, we prepared and characterized persimmon vinegar polyphenols (PVP) in this study. Furthermore, we investigated the protective effect of PVP on hydrogen peroxide (H2 O2 )-induced oxidative stress in HepG2 cells and its underlying mechanisms. Our results showed that flavon-3-ols were the predominant polyphenols in PVP. Pre-treatment with PVP significantly decreased (p < 0.05) H2 O2 -induced cell damage in a dose-dependent manner, accompanied by decrease in lactate dehydrogenase (LDH) leakage, aminotransferase activities, and ROS accumulation...
July 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29570846/neuroprotective-effects-of-creatine-in-the-cmvmjd135-mouse-model-of-spinocerebellar-ataxia-type-3
#20
Sara Duarte-Silva, Andreia Neves-Carvalho, Carina Soares-Cunha, Joana M Silva, Andreia Teixeira-Castro, Rita Vieira, Anabela Silva-Fernandes, Patrícia Maciel
BACKGROUND AND OBJECTIVE: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine-enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which no treatment is available. METHODS: We performed 2 independent preclinical trials using the CMVMJD135 mouse model (treating 2 groups of animals with different disease severity) and wild-type mice, to which 2% creatine was provided for 19 (preclinical trial 1) or 29 (preclinical trial 2) weeks, starting at a presymptomatic age...
March 23, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
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