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https://www.readbyqxmd.com/read/28534853/the-1-tosylpentan-3-one-protects-against-6-hydroxydopamine-induced-neurotoxicity
#1
Chien-Jen Kao, Wu-Fu Chen, Bo-Lin Guo, Chien-Wei Feng, Han-Chun Hung, Wen-Ya Yang, Chun-Sung Sung, Kuan-Hao Tsui, Hsin Chu, Nan-Fu Chen, Zhi-Hong Wen
Previous studies have demonstrated that the marine compound austrasulfone, isolated from the soft coral Cladiella australis, exerts a neuroprotective effect. The intermediate product in the synthesis of austrasulfone, dihydroaustrasulfone alcohol, attenuates several inflammatory responses. The present study uses in vitro and in vivo methods to investigate the neuroprotective effect of dihydroaustrasulfone alcohol-modified 1-tosylpentan-3-one (1T3O). Results from in vitro experiments show that 1T3O effectively inhibits 6-hydroxydopamine-induced (6-OHDA-induced) activation of both p38 mitogen-activated protein kinase (MAPK) and caspase-3 in SH-SY5Y cells; and enhances nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534518/cdk20-interacts-with-keap1-to-activate-nrf2-and-promotes-radiochemoresistance-in-lung-cancer-cells
#2
Q Wang, J Ma, Y Lu, S Zhang, J Huang, J Chen, J-X Bei, K Yang, G Wu, K Huang, J Chen, S Xu
Radiochemoresistance is considered the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radiochemoresistance remain to be uncovered. In this study, we determine the functions of cell cycle-related kinase (CDK20) in radiochemoresistance. CDK20 is a newly identified protein kinase, which plays critical roles in cell growth and proliferation in several types of cancer. Using tandem affinity purification technology, we provide evidences that CDK20 binds to the ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1), which targets transcriptional factor nuclear factor erythroid-2-related factor 2 (NRF2) for degradation...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534275/sex-bias-in-pathogenesis-of-autoimmune-neuroinflammation-relevance-for-dimethyl-fumarate-immunomodulatory-anti-oxidant-action
#3
Zorica Stojić-Vukanić, Jelena Kotur-Stevuljević, Mirjana Nacka-Aleksić, Duško Kosec, Ivana Vujnović, Ivan Pilipović, Mirjana Dimitrijević, Gordana Leposavić
In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28533375/keap1-modifying-small-molecule-reveals-muted-nrf2-signaling-responses-in-neural-stem-cells-from-huntington-s-disease-patients
#4
Luisa Quinti, Sharadha Dayalan Naidu, Ulrike Träger, Xiqun Chen, Kimberly Kegel-Gleason, David Llères, Colúm Connolly, Vanita Chopra, Cho Low, Sébastien Moniot, Ellen Sapp, Adelaide R Tousley, Petr Vodicka, Michael J Van Kanegan, Linda S Kaltenbach, Lisa A Crawford, Matthew Fuszard, Maureen Higgins, James R C Miller, Ruth E Farmer, Vijay Potluri, Susanta Samajdar, Lisa Meisel, Ningzhe Zhang, Andrew Snyder, Ross Stein, Steven M Hersch, Lisa M Ellerby, Eranthie Weerapana, Michael A Schwarzschild, Clemens Steegborn, Blair R Leavitt, Alexei Degterev, Sarah J Tabrizi, Donald C Lo, Marian DiFiglia, Leslie M Thompson, Albena T Dinkova-Kostova, Aleksey G Kazantsev
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28529569/advanced-glycation-end-products-influence-oral-cancer-cell-survival-via-bcl-xl-and-nrf-2-regulation-in-vitro
#5
Shun-Yao Ko, Hshin-An Ko, Tzong-Ming Shieh, Tzong-Cherng Chi, Hong-I Chen, Yi-Ting Chen, Ya-Hui Yu, Shu-Han Yang, Shu-Shing Chang
An irreversible non-enzymatic reaction between carbohydrates and proteins results in the formation of advanced glycation end products (AGEs). AGEs have been demonstrated to be a risk factor of complications in patients with diabetes mellitus (DM). Previous studies have suggested that patients with DM exhibit a higher rate of metastasis of oral cancer and a lower cancer-associated survival rate. The receptor for AGEs (RAGE) has been associated with angiogenesis and an increase in cancer malignancy. Previous studies have suggested that AGE-RAGE regulates cell migration via extracellular signal-regulated kinase (ERK) phosphorylation...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529531/the-protective-effect-of-lavender-essential-oil-and-its-main-component-linalool-against-the-cognitive-deficits-induced-by-d-galactose-and-aluminum-trichloride-in-mice
#6
Pan Xu, Kezhu Wang, Cong Lu, Liming Dong, Li Gao, Ming Yan, Silafu Aibai, Yanyan Yang, Xinmin Liu
Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimer's disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28526682/aeroallergens-induce-reactive-oxygen-species-production-and-dna-damage-and-dampen-antioxidant-responses-in-bronchial-epithelial-cells
#7
Tze Khee Chan, W S Daniel Tan, Hong Yong Peh, W S Fred Wong
Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526034/differential-darc-ackr1-expression-distinguishes-venular-from-non-venular-endothelial-cells-in-murine-tissues
#8
Aude Thiriot, Carolina Perdomo, Guiying Cheng, Igor Novitzky-Basso, Sara McArdle, Jamie K Kishimoto, Olga Barreiro, Irina Mazo, Robinson Triboulet, Klaus Ley, Antal Rot, Ulrich H von Andrian
BACKGROUND: Intravascular leukocyte recruitment in most vertebrate tissues is restricted to postcapillary and collecting venules, whereas capillaries and arterioles usually support little or no leukocyte adhesion. This segmental restriction is thought to be mediated by endothelial, rather than hemodynamic, differences. The underlying mechanisms are largely unknown, in part because effective tools to distinguish, isolate, and analyze venular endothelial cells (V-ECs) and non-venular endothelial cells (NV-ECs) have been unavailable...
May 19, 2017: BMC Biology
https://www.readbyqxmd.com/read/28525375/ros-enhance-angiogenic-properties-via-regulation-of-nrf2-in-tumor-endothelial-cells
#9
Takayuki Hojo, Nako Maishi, Alam Mohammad Towfik, Kosuke Akiyama, Noritaka Ohga, Masanobu Shindoh, Yasuhiro Hida, Kazuyuki Minowa, Toshiaki Fujisawa, Kyoko Hida
Reactive oxygen species (ROS) are unstable molecules that activate oxidative stress. Because of the insufficient blood flow in tumors, the tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation, which induces ROS accumulation. We isolated tumor endothelial cells (TECs) and found that they have various abnormalities, although the underlying mechanisms are not fully understood. Here we showed that ROS were accumulated in tumor blood vessels and ROS enhanced TEC migration with upregulation of several angiogenesis related gene expressions...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523571/congenital-immature-pure-erythroid-leukemia-with-e-cadherin-expression
#10
Akihiro Tamura, Suguru Uemura, Atsuro Saito, Saki Okubo, Nanako Nino, Teppei Tahara, Takehito Yokoi, Kenji Kishimoto, Toshiaki Ishida, Daiichiro Hasegawa, Keiichiro Kawasaki, Seiji Yoshimoto, Hideto Nakao, Makiko Yoshida, Yoshiyuki Kosaka
Congenital pure erythroid leukemia is exceedingly rare and poses a diagnostic challenge. We report an atypical case of congenital pure erythroid leukemia that did not express typical erythroid markers. The patient presented with a high white blood cell count with blastic cells at birth. Although flow cytometric analyses of peripheral blood and bone marrow showed a large CD45-negative cell population, we did not identify any evidence of monoclonality. While the circulating blasts decreased with only supportive care, hepatomegaly with multiple nodules was accompanied by liver failure, disseminated intravascular coagulation, and development of hemophagocytic lymphohistiocytosis...
May 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28522560/the-effect-of-long-term-maternal-smoking-on-the-offspring-s-lung-health
#11
Suporn Sukjamnong, Yik Lung Chan, Razia Zakarya, Sonia Saad, Pawan Sharma, Rachana Santiyanont, Hui Chen, Brian G G Oliver
Maternal smoking during pregnancy contributes to long-term health problems in offspring, especially respiratory disorders which can manifest in either childhood or adulthood. Receptors for advanced glycation end-products (RAGE) are multi-ligand receptors abundantly localized in the lung, capable of responding to by-products of reactive oxygen species and pro-inflammatory responses. RAGE signalling is a key regulator of inflammation in cigarette smoking-related pulmonary diseases. However, the impact of maternal cigarette smoke exposure on lung RAGE signalling in the offspring is unclear...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28522335/comparative-analysis-of-transcriptomic-responses-to-repeated-dose-exposure-to-2-mcpd-and-3-mcpd-in-rat-kidney-liver-and-testis
#12
Thorsten Buhrke, Katharina Schultrich, Albert Braeuning, Alfonso Lampen
3-Chloro-1,2-propanediol (3-MCPD) and its isomer 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants present in oil- and fat-containing foodstuff. Kidney and testes are among the main target organs of 3-MCPD. Almost no data on 2-MCPD toxicity are available. Here, transcriptomic responses following repeated-dose exposure of rats to non-toxic doses of 10 mg/kg body weight 2-MCPD or 3-MCPD for 28 days were characterized by microarray analysis of kidney, liver, and testes. 3-MCPD exerted more pronounced effects than 2-MCPD in all organs...
May 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28522192/overcoming-photodynamic-resistance-and-tumor-targeting-dual-therapy-mediated-by-indocyanine-green-conjugated-gold-nanospheres
#13
Wei Li, Xiaomeng Guo, Fenfen Kong, Hanbo Zhang, Lihua Luo, Qingpo Li, Chunqi Zhu, Jie Yang, Yongzhong Du, Jian You
Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS)...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#14
Ivan Krivega, Ann Dean
Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520765/an-integrative-analysis-of-tissue-specific-transcriptomic-and-metabolomic-responses-to-short-term-dietary-methionine-restriction-in-mice
#15
Sujoy Ghosh, Laura A Forney, Desiree Wanders, Kirsten P Stone, Thomas W Gettys
Dietary methionine restriction (MR) produces a coordinated series of transcriptional responses in peripheral tissues that limit fat accretion, remodel lipid metabolism in liver and adipose tissue, and improve overall insulin sensitivity. Hepatic sensing of reduced methionine leads to induction and release of fibroblast growth factor 21 (FGF21), which acts centrally to increase sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has direct effects in adipose to enhance glucose uptake and oxidation...
2017: PloS One
https://www.readbyqxmd.com/read/28518138/betulin-exhibits-anti-inflammatory-activity-in-lps-stimulated-macrophages-and-endotoxin-shocked-mice-through-an-ampk-akt-nrf2-dependent-mechanism
#16
Xinxin Ci, Junfeng Zhou, Hongming Lv, Qinlei Yu, Liping Peng, Shucheng Hua
Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28515695/chronic-endurance-exercise-impairs-cardiac-structure-and-function-in-middle-aged-mice-with-impaired-nrf2-signaling
#17
Gobinath Shanmugam, Madhusudhanan Narasimhan, Robbie L Conley, Thiagarajan Sairam, Ashutosh Kumar, Ronald P Mason, Ramalingam Sankaran, John R Hoidal, Namakkal S Rajasekaran
Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling maintains the redox homeostasis and its activation is shown to suppress cardiac maladaptation. Earlier we reported that acute endurance exercise (2 days) evoked antioxidant cytoprotection in young WT animals but not in aged WT animals. However, the effect of repeated endurance exercise during biologic aging (WT) characterized by an inherent deterioration in Nrf2 signaling and pathological aging (pronounced oxidative susceptibility-Nrf2 absence) in the myocardium remains elusive...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28515676/low-dose-dose-response-for-in-vitro-nrf2-are-activation-in-human-hepg2-cells
#18
Kenneth T Bogen
Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-like factor 2-related factor 2 (Nrf2), and the antioxidant response element (ARE) are interacting components of a master regulatory signaling pathway that coordinates redox homeostasis, cytoprotective responses, and shifts in stem cell state. This study reexamined detailed dose-response (DR) data reported for in vitro Nrf2-ARE activation in human hepatoblastoma HepG2 cell lines containing either a ARE-bla or ARE-luc reporter at 12 different concentrations of each of 15 chemicals...
April 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28515158/the-anti-psoriatic-drug-monomethylfumarate-increases-nuclear-factor-erythroid-2-related-factor-2-nrf2-levels-and-induces-aquaporin-3-aqp3-mrna-and-protein-expression
#19
Inas Helwa, Vivek Choudhary, Xunsheng Chen, Ismail Kaddour-Djebbar, Wendy B Bollag
BACKGROUND: Oxidative stress contributes to inflammatory skin diseases including psoriasis. Monomethylfumarate (MMF) is an anti-psoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular anti-oxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. OBJECTIVE: We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses...
May 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28513870/activation-of-the-nrf2-are-signaling-pathway-prevents-hyperphosphatemia-induced-vascular-calcification-by-inducing-autophagy-in-renal-vascular-smooth-muscle-cells
#20
Li Yao, Jian Wang, Bin-Yao Tian, Tian-Hua Xu, Zi-Tong Sheng
This study investigates the effect of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in vascular calcification (VC) via inducing Autophagy in renal vascular smooth muscle cells (VSMCs). VSMCs were assigned into six experimental groups: the normal control, high phosphorus, si-negative control (si-NC), Nrf2-siRNA, over-expressed Nrf2 and negative control (NC) groups. RT-PCR was applied to detect the mRNA expressions of the desired Nrf2-ARE signaling pathway-related genes (Nrf2, NQO-1, HO-1, γ-GCS)...
May 17, 2017: Journal of Cellular Biochemistry
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