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https://www.readbyqxmd.com/read/29352001/keap1-editing-using-crispr-cas9-for-therapeutic-nrf2-activation-in-primary-human-t-lymphocytes
#1
Sanjeev Noel, Sul A Lee, Mohanraj Sadasivam, Abdel R A Hamad, Hamid Rabb
Oxidant stress modifies T lymphocyte activation and function. Previous work demonstrated that murine T cell-specific kelch like-ECH-associated protein 1 (Keap1) deletion enhances antioxidant capacity and protects from experimental acute kidney injury. In this study, we used CRISPR technology to develop clinically translatable human T cell-specific KEAP1 deletion. Delivery of KEAP1 exon 2 specific Cas9:guide RNA in Jurkat T cells led to significant (∼70%) editing and upregulation of NRF2-regulated antioxidant genes NADPH dehydrogenase quinone 1 (NQO1) (up to 11-fold), heme oxygenase 1 (HO1) (up to 11-fold), and GCLM (up to 2-fold)...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29351455/thrombosis-systemic-and-cardiac-oxidative-stress-and-dna-damage-induced-by-pulmonary-exposure-to-diesel-exhaust-particles-and-the-effect-of-nootkatone-thereon
#2
Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Badreldin H Ali
Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particles-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. However, its protective effect on the cardiovascular injury induced by diesel exhaust particles (DEP) has not been studied before...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351230/comparison-of-antioxidative-effects-of-insect-tea-and-its-raw-tea-kuding-tea-polyphenols-in-kunming-mice
#3
Xin Zhao, Jia-Le Song, Ruokun Yi, Guijie Li, Peng Sun, Kun-Young Park, Huayi Suo
Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge precipitation. The present study was designed to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by gavage...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29351226/curcumin-attenuates-on-carbon-tetrachloride-induced-acute-liver-injury-in-mice-via-modulation-of-the-nrf2-ho-1-and-tgf-%C3%AE-1-smad3-pathway
#4
Xinyan Peng, Chongshan Dai, Quanwen Liu, Junke Li, Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl₄)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl₄ exposure. At 24 h, curcumin-attenuated CCl₄ induced elevated serum transaminase activities and histopathological damage in the mouse's liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl₄-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29349677/mercuric-chloride-induced-ovarian-oxidative-stress-by-suppressing-nrf2-keap1-signal-pathway-and-its-downstream-genes-in-laying-hens
#5
Yan Ma, Mingkun Zhu, Liping Miao, Xiaoyun Zhang, Xinyang Dong, Xiaoting Zou
The present study evaluated the effects of mercury chloride (HgCl2) on follicular atresia rate, sex hormone secretion, and ovarian oxidative stress in laying hens. Antioxidant enzyme genes and the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signal pathway were further studied to uncover the molecular mechanism. A total of 768 40-week-old Hy-Line Brown laying hens were randomly allocated to four treatments with eight pens per treatment and 24 hens of each pen...
January 18, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29348534/anti-cancer-activities-of-allyl-isothiocyanate-and-its-conjugated-silicon-quantum-dots
#6
Peng Liu, Mehrnaz Behray, Qi Wang, Wei Wang, Zhigang Zhou, Yimin Chao, Yongping Bao
Allyl isothiocyanate (AITC), a dietary phytochemical in some cruciferous vegetables, exhibits promising anticancer activities in many cancer models. However, previous data showed AITC to have a biphasic effect on cell viability, DNA damage and migration in human hepatoma HepG2 cells. Moreover, in a 3D co-culture of HUVEC with pericytes, it inhibited tube formation at high doses but promoted this at low doses, which confirmed its biphasic effect on angiogenesis. siRNA knockdown of Nrf2 and glutathione inhibition abolished the stimulation effect of AITC on cell migration and DNA damage...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348410/oxidative-stress-via-inhibition-of-the-mitochondrial-electron-transport-and-nrf-2-mediated-anti-oxidative-response-regulate-the-cytotoxic-activity-of-plumbagin
#7
Arvinder Kapur, Thomas Beres, Kavya Rathi, Amruta P Nayak, Austin Czarnecki, Mildred Felder, Amani Gillette, Spencer S Ericksen, Emmanuel Sampene, Melissa C Skala, Lisa Barroilhet, Manish S Patankar
Plumbagin, an anti-cancer agent, is toxic to cells of multiple species. We investigated if plumbagin targets conserved biochemical processes. Plumbagin induced DNA damage and apoptosis in cells of diverse mutational background with comparable potency. A 3-5 fold increase in intracellular oxygen radicals occurred in response to plumbagin. Neutralization of the reactive oxygen species by N-acetylcysteine blocked apoptosis, indicating a central role for oxidative stress in plumbagin-mediated cell death. Plumbagin docks in the ubiquinone binding sites (Q0 and Qi) of mitochondrial complexes I-III, the major sites for oxygen radicals...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29344655/protective-effects-of-osthole-against-inflammation-induced-by-lipopolysaccharide-in-bv2-cells
#8
Yuxin Bao, Xiaolin Meng, Fangning Liu, Fei Wang, Jinhui Yang, Haiyu Wang, Guanghong Xie
Inflammation and oxidative stress are implicated in the development of neurodegenerative diseases. Osthole is a compound that is extracted from She Chuang Zi, which is a type of traditional Chinese medicine. Osthole has previously been demonstrated to exhibit anticancer activities and has a low toxicity. However, to the best of our knowledge, the anti‑inflammatory effects of osthole in microglial cells have not been investigated extensively. The aim of the present study was to investigate the potential protective effects of osthole against inflammation induced by lipopolysaccharide (LPS) in microglial cells...
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
#9
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/29341114/recombinant-human-hepatocyte-growth-factor-provides-protective-effects-in-celurein-induced-acute-pancreatitis-in-mice
#10
Mayrel Palestino-Domínguez, Mario Pelaez-Luna, Roberto Lazzarini-Lechuga, Ignacio Rodríguez-Ochoa, Verónica Souza, Roxana U Miranda, Benjamín Pérez-Aguilar, Leticia Bucio, Jens U Marquardt, Luis Enrique Gomez-Quiroz, María Concepción Gutiérrez-Ruiz
Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c-Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein-induced acute pancreatitis...
January 17, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29340219/a-novel-hybrid-promoter-are-htert-for-cancer-gene-therapy
#11
S V Kalinichenko, M V Shepelev, P N Vikhreva, I V Korobko
describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the human GCLM gene promoter. The hybrid promoter retains the tumor specificity of the basal hTERT promoter but is characterized by an enhanced transcriptional activity in cancer cells with abnormal activation of the Nrf2 transcription factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein induced a more pronounced death of cancer cells either upon treatment with 5-fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as compared to the hTERT promoter...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339380/negative-regulation-of-the-keap1-nrf2-pathway-by-a-p62-sqstm1-splicing-variant
#12
Shun Kageyama, Tetsuya Saito, Miki Obata, Ryo-Hei Koide, Yoshinobu Ichimura, Masaaki Komatsu
A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via multiple mechanisms, including gene expression, post-translational modifications such as ubiquitination and phosphorylation, and autophagic degradation of p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl database search and subsequent biochemical analyses in mice revealed the presence of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region (KIR), which is essential for the interaction with Keap1...
January 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339045/deficiency-of-dietary-pyridoxine-disturbed-the-intestinal-physical-barrier-function-of-young-grass-carp-ctenopharyngodon-idella
#13
Pei Wu, Xin Zheng, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Yong-An Zhang, Lin Feng
The aim of this study was to assess the effects of dietary pyridoxine (PN) deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular tight junction in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (231.85 ± 0.63 g) were fed six diets containing graded levels of PN (0.12-7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed that compared with the optimal PN level, PN deficiency (1) increased the contents of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC), decreased the activities and mRNA levels of antioxidant enzymes such as copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) (P < ...
January 12, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29339024/nrf2-are-pathway-attenuates-oxidative-and-apoptotic-response-in-human-osteoarthritis-chondrocytes-by-activating-erk1-2-elk1-p70s6k-p90rsk-signaling-axis
#14
Nazir M Khan, Imran Ahmad, Tariq M Haqqi
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1β stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient...
January 12, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29338970/baicalein-and-baicalin-alleviate-acetaminophen-induced-liver-injury-by-activating-nrf2-antioxidative-pathway-the-involvement-of-erk1-2-and-pkc
#15
Liang Shi, Zhanxia Hao, Shaobo Zhang, Mengjuan Wei, Bin Lu, Zhengtao Wang, Lili Ji
Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, baicalin-provided this protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury...
January 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29338543/lucidone-suppresses-dengue-viral-replication-through-the-induction-of-heme-oxygenase-1
#16
Wei-Chun Chen, Chin-Kai Tseng, Chun-Kuang Lin, Shen-Nien Wang, Wen-Hung Wang, Shih-Hsien Hsu, Yu-Hsuan Wu, Ling-Chien Hung, Yen-Hsu Chen, Jin-Ching Lee
Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29338172/activation-of-nrf2-and-hypoxic-adaptive-response-contribute-to-neuroprotection-elicited-by-phenylhydroxamic-acid-selective-hdac6-inhibitors
#17
Irina N Gaisina, Sue H Lee, Navneet A Kaidery, Manel Ben Aissa, Manuj Ahuja, Natalya N Smirnova, Sushama Wakade, Arsen Gaisin, Megan W Bourassa, Rajiv R Ratan, Sergey V Nikulin, Andrey A Poloznikov, Bobby Thomas, Gregory R J Thatcher, Irina G Gazaryan
Activation of HIF-1α and Nrf2 is a primary component of cellular response to oxidative stress, and activation of HIF-1α and Nrf2 provides neuroprotection in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel reporters for HIF-1α and Nrf2 elevation in neuronal cells revealed histone deacetylase (HDAC) inhibitors as potential activators of these pathways. We report the identification of phenylhydroxamates as single agents exhibiting tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and activation of Nrf2...
January 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29337893/soybean-derived-phytoalexins-improve-cognitive-function-through-activation-of-nrf2-ho-1-signaling-pathway
#18
Ji Yeon Seo, Bo Ram Kim, Jisun Oh, Jong-Sang Kim
As soy-derived glyceollins are known to induce antioxidant enzymes in various types of cells and tissues, we hypothesized that the compounds could protect neurons from damage due to reactive oxygen species (ROS). In order to examine the neuroprotective effect of glyceollins, primary cortical neurons collected from mice and mouse hippocampal HT22 cells were challenged with glutamate. Glyceollins attenuated glutamate-induced cytotoxicity in primary cortical neuron isolated from mice carrying wild-type nuclear factor (erythroid-derived 2)-like 2 (Nrf2), but the compounds were ineffective in those isolated from Nrf2 knockout mice, suggesting the involvement of the Nrf2 signaling pathway in glyceollin-mediated neuroprotection...
January 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29336610/nrf2-are-and-nf-%C3%AE%C2%BAb-pathway-regulation-may-be-the-mechanism-for-lutein-inhibition-of-human-breast-cancer-cell
#19
Jingzhi Chang, Yuxia Zhang, Yichuan Li, Kun Lu, Yongjie Shen, Yali Guo, Qingfeng Qi, Mingchen Wang, Shanfeng Zhang
AIM: Though lutein can inhibit cancer cell proliferation via alleviating oxidative injury, the molecular mechanisms of lutein involvement in the NrF2/antioxidant response element (ARE) and NF-κB pathways remain poorly understood. MATERIALS & METHODS: MTT, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blot assays were performed. RESULTS: After treatment with lutein, breast cancer cell proliferation was significantly decreased in a dose-dependent manner...
January 16, 2018: Future Oncology
https://www.readbyqxmd.com/read/29335845/carnosic-acid-as-a-promising-agent-in-protecting-mitochondria-of-brain-cells
#20
REVIEW
Marcos Roberto de Oliveira
Carnosic acid (CA; C20H28O4), a phenolic diterpene characterized as an ortho-dihydroquinone-type molecule, is a pro-electrophile agent that becomes an electrophile after reacting with free radicals. The electrophile generated from CA interacts with and activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which is a major modulator of redox biology in mammalian cells. CA induces antioxidant and anti-inflammatory effects in several cell types, as observed in both in vitro and in vivo experimental models...
January 15, 2018: Molecular Neurobiology
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