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Aaron J Done, Tinna Traustadóttir
The primary aim of this review is to summarize the current literature on the effects of acute exercise and regular exercise on nuclear factor erythroid 2-related factor 2 (Nrf2) activity and downstream targets of Nrf2 signaling. Nrf2 (encoded in humans by the NFE2L2 gene) is the master regulator of antioxidant defenses, a transcription factor that regulates expression of more than 200 cytoprotective genes. Increasing evidence indicates that Nrf2 signaling plays a key role in how oxidative stress mediates the beneficial effects of exercise...
October 14, 2016: Redox Biology
Virve Sihvola, Anna-Liisa Levonen
Reactive oxygen species (ROS) and products of their reactions with cellular macromolecules such as unsaturated fatty acids have been implicated to be important regulators of signalling processes via oxidation or alkylation of redox active thiol residues in target proteins. One of key redox-sensitive signalling proteins mediating the response to oxidant stress is Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1), which is a negative regulator of transcription factor Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and the central hub for sensing endogenous and environmental oxidative and electrophilic stress...
October 18, 2016: Archives of Biochemistry and Biophysics
Izabela Jatczak-Pawlik, Michal Gorzkiewicz, Maciej Studzian, Dietmar Appelhans, Brigitte Voit, Lukasz Pulaski, Barbara Klajnert-Maculewicz
PURPOSE: Fourth-generation poly(propylene imine) dendrimers fully surface-modified by maltose (dense shell, PPI-m DS) were shown to be biocompatible in cellular models, which is important for their application in drug delivery. We decided to verify also their inherent bioactivity, including immunomodulatory activity, for potential clinical applications. We tested their effects on the THP-1 monocytic cell line model of innate immunity effectors. METHODS: To estimate the cytotoxicity of dendrimers the reasazurin assay was performed...
October 20, 2016: Pharmaceutical Research
Hui-Mei Lee, Vyomesh Patel, Lie-Fen Shyur, Wai-Leng Lee
BACKGROUND: Oral cancer is the sixth most common cancer worldwide and 90% of oral malignancies are caused by oral squamous cell carcinoma (OSCC). Curcumin, a phytocompound derived from turmeric (Curcuma longa) was observed to have anti-cancer activity which can be developed as an alternative treatment option for OSCC. However, OSCC cells with various clinical-pathological features respond differentially to curcumin treatment. HYPOTHESIS: Intracellular copper levels have been reported to correlate with tumor pathogenesis and affect the sensitivity of cancer cells to cytotoxic chemotherapy...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Zhengwang Sun, Sang Yong Park, Eunson Hwang, Bom Park, Seul A Seo, Jin-Gyeong Cho, Mengyang Zhang, Tae-Hoo Yi
BACKGROUND: Foeniculum vulgare Mill (FV) has long been prescribed in traditional medicine due to its antioxidant anti-inflammatory properties. However, little research has been done on the use of FV to alleviate changes in UVB-induced photoaging PURPOSE: This study was to investigate the photoprotective effects and mechanism of FV in vitro and in vivo. METHODS: The anti-photoaging effect of FV was assessed in normal human dermal fibroblasts (NHDFs) in vitro. The secretion of reactive oxygen species (ROS), lactate dehydrogenase (LDH), GSH, matrix metalloproteinases (MMPs), procollagen type I, IL-6 and transforming growth factor-β1 (TGF-β1) were measured by kits...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Chunfeng Lu, Wenxuan Xu, Feng Zhang, Jiangjuan Shao, Shizhong Zheng
It has emerged that hepatocyte necroptosis plays a critical role in chronic alcoholic liver disease (ALD). Our previous study has identified that the beneficial therapeutic effect of curcumin on alcohol-caused liver injury might be attributed to activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), whereas the role of curcumin in regulating necroptosis and the underlying mechanism remain to be determined. We firstly found that chronic alcohol consumption triggered obvious hepatocyte necroptosis, leading to increased expression of receptor-interacting protein 1, receptor-interacting protein 3, high-mobility group box 1, and phosphorylated mixed lineage kinase domain-like in murine livers...
October 20, 2016: Molecular Pharmaceutics
Jing Li, Jun Zhou, Yuanhua Ye, Qunying Liu, Xiaojin Wang, Ning Zhang, Xietong Wang
BACKGROUND: Previous studies have shown that oxidative stress is an important factor in preeclampsia (PE). Heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor-2 (Nrf2) are protective proteins that are involved in combating oxidative stress in the body. Nrf2 is also an essential upstream transcription factor regulating HO-1. This study was aimed at exploring the physiological roles of HO-1 and Nrf2 in PE. METHODS: Serum and placenta were collected from 30 patients who presented with severe PE and 30 healthy pregnant females...
October 21, 2016: Gynecologic and Obstetric Investigation
Pei Y Liu, Nicholas Sokolowski, Su T Guo, Faraz Siddiqi, Bernard Atmadibrata, Thomas J Telfer, Yuting Sun, Lihong Zhang, Denise Yu, Joshua Mccarroll, Bing Liu, Rui H Yang, Xiang Y Guo, Andrew E Tee, Ken Itoh, Jenny Wang, Maria Kavallaris, Michelle Haber, Murray D Norris, Belamy B Cheung, Jennifer A Byrne, David S Ziegler, Glenn M Marshall, Marcel E Dinger, Rachel Codd, Xu D Zhang, Tao Liu
BET bromodomain inhibitors are very promising novel anticancer agents, however, single therapy does not cause tumor regression in mice, suggesting the need for combination therapy. After screening a library of 2697 small molecule compounds, we found that two classes of compounds, the quinone-containing compounds such as nanaomycin and anti-microtubule drugs such as vincristine, exerted the best synergistic anticancer effects with the BET bromodomain inhibitor JQ1 in neuroblastoma cells. Mechanistically, the quinone-containing compound nanaomycin induced neuroblastoma cell death but also activated the Nrf2-antioxidant signaling pathway, and the BET bromodomain proteins BRD3 and BRD4 formed a protein complex with Nrf2...
October 13, 2016: Oncotarget
Jihe Li, Dongxia Tong, Juan Liu, Fuyang Chen, Yongbin Shen
Oroxylin A, a natural flavonoid isolated from the medicinal herb Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory and antioxidant properties. However, the effect of oroxylin A on cigarette smoke (CS)-induced lung inflammation remains unclear. In this study, the ability of oroxylin A to protect against CS-induced lung inflammation was detected in vivo and in vitro. Oroxylin A was administered intraperitoneally to mice 2h prior CS exposure every day for five consecutive days. BEAS-2B bronchial epithelial cells and RAW264...
October 17, 2016: International Immunopharmacology
Chia-Sheng Chao, Chien-Sung Tsai, Yee-Phoung Chang, Jian-Ming Chen, Hsien-Kuo Chin, Shyh-Chyun Yang
Hyperin, a flavonoid compound found in Ericaceae, Guttiferae, and Celastraceae, has been reported to have anti-inflammatory effects. In the present study, we investigated the effects of hyperin on cisplatin-induced acute kidney injury (AKI) in mice. The renal tissue damage induced by cisplatin was detected by H&E staining. Blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), and malondialdehyde (MDA) were also detected. Further, the effects of hyperin on cisplatin-induced TNF-α, IL-1β and IL-6 were detected by ELISA...
October 17, 2016: International Immunopharmacology
Chien-Wei Feng, Han-Chun Hung, Shi-Ying Huang, Chun-Hong Chen, Yun-Ru Chen, Chun-Yu Chen, San-Nan Yang, Hui-Min David Wang, Ping-Jyun Sung, Jyh-Horng Sheu, Kuan-Hao Tsui, Wu-Fu Chen, Zhi-Hong Wen
Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways...
October 17, 2016: Marine Drugs
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Yunlong Shan, Zhonghong Wei, Li Tao, Siliang Wang, Feng Zhang, Cunsi Shen, Hongyan Wu, Zhaoguo Liu, Pingting Zhu, Aiyun Wang, Wenxing Chen, Yin Lu
Cancer prevention through intake of biologically active natural products appears to be an accessible way to reduce the risk of cancer. Diallyl disulfide (DADS), a major garlic derivative, has exhibited potential role in cancer therapy. The study is aimed to evaluate the prophylactic effect of DADS in chemically induced mouse skin carcinogenesis and investigate the molecular targets mediated by DADS. Two-stage chemically induced carcinogenesis model by cutaneous application of DMBA and subsequent TPA was established to study the prophylactic effect of DADS...
October 19, 2016: Scientific Reports
Yingze Wei, Danyang Liu, Xiaoxia Jin, Pan Gao, Qingying Wang, Jiawen Zhang, Nong Zhang
Acquired resistance to doxorubicin in breast cancer is a serious therapeutic problem. In this study, we investigated whether Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) could inhibit the growth of doxorubicin-resistant breast cancer cells. We found that the expressions of Nrf2 and p62 in breast cancer were higher than that in the corresponding adjacent normal tissues and benign breast epithelial cell. The expressions of Nrf2 and p62 in breast cancer doxorubicin-resistant cells MCF-7/ADR were higher than that in doxorubicin-sensitive cells MCF-7...
October 18, 2016: Cancer Medicine
Masaki Sunagawa, Shinji Mii, Atsushi Enomoto, Takuya Kato, Yoshiki Murakumo, Yukihiro Shiraki, Naoya Asai, Masato Asai, Masato Nagino, Masahide Takahashi
CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in several types of human cancers, particularly squamous cell carcinomas. We previously reported that CD109-deficient mice exhibit epidermal hyperplasia and chronic skin inflammation. Although we found that CD109 regulates differentiation of keratinocytes in vivo, the function of CD109 in tumorigenesis remains unknown. In this study, we investigated the role of CD109 in skin tumorigenesis using a two-stage carcinogenesis model in CD109-deficient mice with chronic skin inflammation...
October 14, 2016: Oncotarget
Francislaine A Dos Reis Lívero, Gracianny Gomes Martins, José Ederaldo Queiroz Telles, Olair Carlos Beltrame, Stellee Marcela Petris Biscaia, Célia Regina Cavichiolo Franco, Ronald P J Oude Elferink, Alexandra Acco
Ethanol abuse is a serious public health problem that is associated with several stages of alcoholic liver disease (ALD) and a high incidence of morbidity and mortality. Alcoholic fatty liver disease (AFLD), the earliest stage of ALD, is a multifactorial injury that involves oxidative stress and disruptions of lipid metabolism. Although benign and reversible, no pharmacological treatments are available for this condition. In the present study, we induced AFLD in mice with 10% ethanol and a low-protein diet and then orally treated them with a hydroethanolic extract of Baccharis trimera (HEBT; 30 mg kg(-1))...
October 15, 2016: Chemico-biological Interactions
Yuxiang Song, Na Li, Jingmin Gu, Shoupeng Fu, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Xiaobing Li, Zhe Wang, Xinwei Li, Guowen Liu
β-Hydroxybutyrate (BHB) is an important indicator for metabolic disorders in dairy cows, such as ketosis and fatty liver. Dairy cows with ketosis display oxidative stress that may be associated with high levels of BHB. The purpose of this study was to demonstrate a correlation between the high levels of BHB and oxidative stress in dairy cows with ketosis, and to investigate the molecular mechanisms underlying oxidative damage in bovine hepatocytes. The results showed that dairy cows with ketosis exhibited oxidative stress and liver damage, which was significantly correlated with plasma BHB...
November 2016: Journal of Dairy Science
Rashi Arora, Sharad Sawney, Vikas Saini, Chris Steffi, Manisha Tiwari, Daman Saluja
BACKGROUND: A handful of studies have exploited antitumor potential of esculetin, a dihydroxy coumarine derivative; the targets to which it binds and the possible downstream mechanism for its cytotoxicity in cancer cells remain to be elucidated. Using pancreatic cancer cell lines as a model system, herein the study was initiated to check the efficacy of esculetin in inhibiting growth of these cancer cells, to decipher mechanism of its action and to predict its direct binding target protein...
October 18, 2016: Molecular Cancer
Shuai Jiang, Yang Yang, Tian Li, Zhiqiang Ma, Wei Hu, Chao Deng, Chongxi Fan, Jianjun Lv, Yang Sun, Wei Yi
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a basic leucine zipper (bZIP) transcription factor of the cap'n'collar (CNC) family that is present in various organs. The cardiovascular system (CVS) is susceptible to a spectrum of diseases that are strongly associated with increased risks of mortality and morbidity, and studies have demonstrated that Nrf2 has a pivotal role in protection against cardiovascular diseases (CVDs). Areas covered: Nrf2 is a basic protective molecule that guards against CVD by attenuating oxidative stress, mitochondrial dysfunction, and inflammation...
October 19, 2016: Expert Opinion on Therapeutic Targets
X Liu, X Zhang, K Ma, R Zhang, P Hou, B Sun, S Yuan, Z Wang, Z Liu
Matrine is a quinolizidine alkaloid derived from the herb Radix Sophorae Flavescentis, and possesses anti-oxidant, anti-inflammatory and anti-tumoral properties. However, its effectiveness against subarachnoid hemorrhage (SAH) is not well known. In this study, we investigated the effects of matrine on early brain injury (EBI) and the related potential mechanisms following SAH in rats. Our results showed that matrine pretreatment partially alleviated SAH-induced EBI, including neurological deficit, severity of SAH grade, brain edema, and blood-brain barrier (BBB) disruption in rats...
September 30, 2016: Cellular and Molecular Biology
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