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https://www.readbyqxmd.com/read/28922594/dose-dependent-response-to-3-nitrobenzanthrone-exposure-in-human-urothelial-cancer-cells
#1
Mario Pink, Nisha Verma, Anna Zerries, Simone Schmitz-Spanke
A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterise the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 µM (environmentally relevant) to 80 µM by utilising toxicological and metabolomic approaches...
September 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#2
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911204/enhanced-vulnerability-of-human-proteins-towards-disease-associated-inactivation-through-divergent-evolution
#3
Encarnación Medina-Carmona, Julian E Fuchs, Jose A Gavira, Noel Mesa-Torres, Jose L Neira, Eduardo Salido, Rogelio Palomino-Morales, Miguel Burgos, David J Timson, Angel L Pey
Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28905938/triptolide-induces-sertoli-cell-apoptosis-in-mice-via-ros-jnk-dependent-activation-of-the-mitochondrial-pathway-and-inhibition-of-nrf2-mediated-antioxidant-response
#4
Yu Wang, Su-Han Guo, Xue-Jun Shang, Li-Sha Yu, Jian-Wei Zhu, Ang Zhao, Yan-Fen Zhou, Guo-Hua An, Qi Zhang, Bo Ma
Triptolide (TP), an oxygenated diterpene, has a variety of beneficial pharmacodynamic activities but its clinical applications are restricted due to severe testicular injury. This study aimed to delineate the molecular mechanisms of TP-induced testicular injury in vitro and in vivo. TP (5-50000 nmol/L) dose-dependently decreased the viability of TM4 Sertoli cells with an IC50 value of 669.5-269.45 nmol/L at 24 h. TP (125, 250, and 500 nmol/L) dose-dependently increased the accumulation of ROS, the phosphorylation of JNK, mitochondrial dysfunction and activation of the intrinsic apoptosis pathway in TM4 cells...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28903401/7-deacetylgedunin-suppresses-inflammatory-responses-through-activation-of-keap1-nrf2-ho-1-signaling
#5
Jian-Yu Chen, Guo-Yuan Zhu, Xiao-Hui Su, Rui Wang, Juan Liu, Kangsheng Liao, Rutong Ren, Ting Li, Liang Liu
Macrophages play a critical role in a variety of inflammatory diseases. Activation of Keap1/Nrf2/HO-1 signaling results in inactivation of macrophages and amelioration of inflammatory and autoimmune conditions. Hence, discovery for the activators of Keap1/Nrf2/HO-1 signaling has become a promising strategy for treatment inflammatory diseases. In the current study, the anti-inflammatory potential of 7-deacetylgedunin (7-DGD), a limonin chemical isolated from the fruits of Toona sinensis (A. Juss.) Roem, was intensively examined in vivo and in vitro for the first time...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28886998/propolis-reversed-cigarette-smoke-induced-emphysema-through-macrophage-alternative-activation-independent-of-nrf2
#6
Marina Valente Barroso, Isabella Cattani-Cavalieri, Lycia de Brito-Gitirana, Alain Fautrel, Vincent Lagente, Martina Schmidt, Luís Cristóvão Porto, Bruna Romana-Souza, Samuel Santos Valença, Manuella Lanzetti
Chronic obstructive pulmonary disease (COPD) is an incurable and progressive disease. Emphysema is the principal manifestation of COPD, and the main cause of this condition is cigarette smoke (CS). Natural products have shown antioxidant and anti-inflammatory properties that can prevent acute lung inflammation and emphysema, but there are few reports in the literature regarding therapeutic approaches to emphysema. We hypothesized that supplementation with natural extracts would repair lung damage in emphysema caused by CS exposure...
August 19, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28883796/functions-of-nqo1-in-cellular-protection-and-coq10-metabolism-and-its-potential-role-as-a-redox-sensitive-molecular-switch
#7
REVIEW
David Ross, David Siegel
NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28881715/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#8
Zipeng Zhou, Chang Liu, Shurui Chen, Haosen Zhao, Kang Zhou, Wei Wang, Yajiang Yuan, Zhuo Li, Yue Guo, Zhaoliang Shen, Xifan Mei
The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879492/molecular-modeling-and-structure-based-drug-discovery-approach-reveals-protein-kinases-as-off-targets-for-novel-anticancer-drug-rh1
#9
Pramodkumar P Gupta, Virupaksha A Bastikar, Dalius Kuciauskas, Shanker Lal Kothari, Jonas Cicenas, Mindaugas Valius
Potential drug target identification and mechanism of action is an important step in drug discovery process, which can be achieved by biochemical methods, genetic interactions or computational conjectures. Sometimes more than one approach is implemented to mine out the potential drug target and characterize the on-target or off-target effects. A novel anticancer agent RH1 is designed as pro-drug to be activated by NQO1, an enzyme overexpressed in many types of tumors. However, increasing data show that RH1 can affect cells in NQO1-independent fashion...
September 6, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28868496/pancreatic-mitochondrial-complex-i-exhibits-aberrant-hyperactivity-in-diabetes
#10
Jinzi Wu, Xiaoting Luo, Nopporn Thangthaeng, Nathalie Sumien, Zhenglan Chen, Margaret A Rutledge, Siqun Jing, Michael J Forster, Liang-Jun Yan
It is well established that NADH/NAD(+) redox balance is heavily perturbed in diabetes, and the NADH/NAD(+) redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD(+) regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS). Yet how complex I responds to the NADH/NAD(+) redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28865326/hydrogen-sulfide-attenuates-calcification-of-vascular-smooth-muscle-cells-via-keap1-nrf2-nqo1-activation
#11
Parisa Aghagolzadeh, Ramin Radpour, Matthias Bachtler, Harry van Goor, Edward R Smith, Adam Lister, Alex Odermatt, Martin Feelisch, Andreas Pasch
BACKGROUND AND AIMS: Vascular calcification is a common health problem related to oxidative stress, inflammation, and circulating calciprotein particles (CPP). Hydrogen sulfide is an endogenous signaling molecule with antioxidant properties and potential for drug development targeting redox signaling. Yet, its molecular mechanisms of action in vascular smooth muscle cell (VSMC) calcification have not been delineated. We therefore sought to identify key pathways involved in the calcification-inhibitory properties of sulfide employing our recently developed CPP-induced VSMC calcification model...
August 19, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28863281/aging-related-decline-in-the-induction-of-nrf2-regulated-antioxidant-genes-in-human-bronchial-epithelial-cells
#12
Lulu Zhou, Hongqiao Zhang, Kelvin J A Davies, Henry Jay Forman
Evidence from animal studies suggests that stress-induced increases in Nrf2-regulated antioxidant gene expression, a critical mechanism of cellular protection, declines with aging. This study examined whether this also occurs in humans. We measured the basal and inducible levels of Nrf2-regulated antioxidant genes in human bronchial epithelial (HBE) cells from subjects of young adult (21-29 years) and older (60-69 years) non-smokers, and explored factors affecting expresion. The basal expression of three representative Nrf2-regulated genes, the catalytic and modulator subunits of glutamate cysteine ligase (GCLC and GCLM, respectively), and NAD(P)H quinone oxidoreductase 1 (NQO1), was higher in cells from the older donors compared with cells from the young adult donors...
August 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28846887/attenuation-of-cyclosporine-a-induced-nephrotoxicity-by-schisandrin-b-through-suppression-of-oxidative-stress-apoptosis-and-autophagy
#13
Qiao Lai, Zhengzhong Luo, Chunying Wu, Sisi Lai, Hanmei Wei, Tongming Li, Qing Wang, Yang Yu
Cyclosporine A (CsA) is a potent immunosuppressive agent whose clinical usage is limited by nephrotoxicity. Schisandrin B (SchB), isolated from the fruit of Schisandra chinensis, is a natural compound with multiple pharmacological activities that has been shown to attenuate organ injury caused by CsA. Hence, the primary objective of the current study was to evaluate whether SchB has a cytoprotective effect on CsA-induced nephrotoxicity in human proximal tubular epithelial cell line (HK-2). This study demonstrated that pre-incubation of HK-2 cells with 2...
August 25, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28844677/procyanidin-b2-ameliorates-carrageenan-induced-chronic-nonbacterial-prostatitis-in-rats-via-anti-inflammatory-and-activation-of-the-nrf2-pathway
#14
Wei Wang, Renzong Chen, Jiye Wang
Prostatitis is one of the most prevalent problems in andriatry and urinary surgery. In the present study, we evaluated the effect of procyanidin B2 (PB) on carrageenan-induced chronic nonbacterial prostatitis in rats. Results showed that PB significantly decreased the prostatic index and enhanced the body weight inhibited by carrageenan. Biochemical results revealed that PB significantly lowered the prostatic specific antigen (PSA) and alleviated oxidative stress in serum. The levels of TNF-α, IL-6, and IL-10 in prostatic homogenate were also significantly decreased after PB treatment...
August 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28843594/safety-assessment-of-the-dietary-supplement-oxyelite%C3%A2-pro-new-formula-in-inbred-and-outbred-mouse-strains
#15
Isabelle R Miousse, Charles M Skinner, Haixia Lin, Laura E Ewing, Stanley D Kosanke, D Keith Williams, Bharathi Avula, Ikhlas A Khan, Mahmoud A ElSohly, Bill J Gurley, Igor Koturbash
Herbal dietary supplements have gained wide acceptance as alternatives to conventional therapeutic agents despite concerns regarding their efficacy and safety. In 2013, a spate of severe liver injuries across the United States was linked to the dietary supplement OxyELITE Pro-New Formula (OEP-NF), a multi-ingredient product marketed for weight loss and exercise performance enhancement. The principal goal of this study was to assess the hepatotoxic potential of OEP-NF in outbred and inbred mouse models. In an acute toxicity study, significant mortality was observed after administering 10X and 3X mouse-equivalent doses (MED) of OEP-NF, respectively...
August 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28833669/a-tumor-specific-cascade-amplification-drug-release-nanoparticle-for-overcoming-multidrug-resistance-in-cancers
#16
Mingzhou Ye, Yuxin Han, Jianbin Tang, Ying Piao, Xiangrui Liu, Zhuxian Zhou, Jianqing Gao, Jianghong Rao, Youqing Shen
A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β-lapachone and a reactive-oxygen-species (ROS)-responsive doxorubicin (DOX) prodrug, BDOX, in polymeric nanoparticles. Releasing β-lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects...
August 21, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28829143/intermolecular-interactions-between-coencapsulated-drugs-inhibit-drug-crystallization-and-enhance-colloidal-stability-of-polymeric-micelles
#17
Ling Zhang, Hanzi Sun, Zhen Chen, Zhengsheng Liu, Niu Huang, Feng Qian
Novel "pairs" of drugs possessing pharmacological synergies could be encapsulated into polymeric micelles and exert superb therapeutic effects in vivo upon intravenous administration, with the prerequisite that the micelles remain stable. NADP(H) quinone oxidoreductase 1 (NQO1) inhibitors, such as β-lapachone (LPC) and tanshinone IIA (THA), are structurally and pharmacologically similar molecules that are poorly water-soluble, crystallize extremely fast, and demonstrate synergistic anticancer effect when used together with paclitaxel (PTX)...
September 1, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28816586/oxidative-stress-in-the-visceral-fat-is-elevated-in-postmenopausal-women-with-gynecologic-cancer
#18
Megumi Narumi, Kazuhiro Takahashi, Hizuru Yamatani, Manabu Seino, Keiko Yamanouchi, Tsuyoshi Ohta, Toshifumi Takahashi, Hirohisa Kurachi, Satoru Nagase
OBJECTIVES: This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women and clarify the antioxidant effect of estrogen on adipocytes. MATERIALS AND METHODS: Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery. We measured the sizes of the adipocytes and evaluated the lipid peroxidation levels in the adipose tissues. We investigated whether estrogen inhibited the intracellular reactive oxygen species (ROS) production that was induced by hydrogen peroxide (H2O2) in 3T3-L1 adipocytes...
August 17, 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/28812892/designer-extracts-as-tools-to-balance-estrogenic-and-chemopreventive-activities-of-botanicals-for-women-s-health
#19
Birgit M Dietz, Shao-Nong Chen, René F Ramos Alvarenga, Huali Dong, Dejan Nikolić, Martin Biendl, Richard B van Breemen, Judy L Bolton, Guido F Pauli
Botanical dietary supplements contain multiple bioactive compounds that target numerous biological pathways. The lack of uniform standardization requirements is one reason that inconsistent clinical effects are reported frequently. The multifaceted biological interactions of active principles can be disentangled by a coupled pharmacological/phytochemical approach using specialized ("knock-out") extracts. This is demonstrated for hops, a botanical for menopausal symptom management. Employing targeted, adsorbent-free countercurrent separation, Humulus lupulus extracts were designed for pre- and postmenopausal women by containing various amounts of the phytoestrogen 8-prenylnaringenin (8-PN) and the chemopreventive constituent xanthohumol (XH)...
August 16, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28798861/overexpression-of-brg1-alleviates-hepatic-ischemia-reperfusion-induced-acute-lung-injury-through-antioxidative-stress-effects
#20
Mian Ge, Chaojin Chen, Weifeng Yao, Shaoli Zhou, Fei Huang, Jun Cai, Ziqing Hei
AIM: To investigate whether overexpression of Brahma-related gene-1 (Brg1) can alleviate lung injury induced by hepatic ischemia/reperfusion (HIR) and its precise mechanism. METHODS: Cytomegalovirus-transgenic Brg1-overexpressing (CMV-Brg1) mice and wild-type (WT) C57BL/6 mice underwent HIR. Lung histology, oxidative injury markers, and antioxidant enzyme concentrations in the lung were assessed. The protein expression levels of Brg1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the lung were analyzed by Western blotting...
2017: Oxidative Medicine and Cellular Longevity
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