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https://www.readbyqxmd.com/read/29342206/silymarin-prevents-acetaminophen-induced-hepatotoxicity-in-mice
#1
Zuzana Papackova, Marie Heczkova, Helena Dankova, Eva Sticova, Alena Lodererova, Lenka Bartonova, Martin Poruba, Monika Cahova
Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination...
2018: PloS One
https://www.readbyqxmd.com/read/29339440/repurposing-tin-mesoporphyrin-as-an-immune-checkpoint-inhibitor-shows-therapeutic-efficacy-in-preclinical-models-of-cancer
#2
Tamara Muliaditan, James W Opzoomer, Jonathan Caron, Mary Okesola, Paris Kosti, Sharanpreet Lall, Mieke Van Hemelrijck, Francesco Dazzi, Andrew Tutt, Anita Grigoriadis, Cheryl Gillett, Stephen F Madden, Joy M Burchell, Shahram Kordasti, Sandra S Diebold, James Spicer, James N Arnold
PURPOSE: Unprecedented clinical outcomes have been achieved in a variety of cancers by targeting immune checkpoint molecules. This preclinical study investigates heme oxygenase-1 (HO-1), an immune suppressive enzyme that is expressed in a wide variety of cancers, as a potential immune checkpoint target in the context of a chemotherapy-elicited anti-tumor immune response. We evaluate repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy targeting hepatic HO in the clinic for the treatment of hyperbilirubinaemia, as an immune checkpoint blockade therapy for the treatment of cancer...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#3
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/29338543/lucidone-suppresses-dengue-viral-replication-through-the-induction-of-heme-oxygenase-1
#4
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/29337893/soybean-derived-phytoalexins-improve-cognitive-function-through-activation-of-nrf2-ho-1-signaling-pathway
#5
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/29336118/resveratrol-potently-counteracts-quercetin-starvation-induced-autophagy-and-sensitizes-hepg2-cancer-cells-to-apoptosis
#6
Sarah Tomas-Hernández, Jordi Blanco, Cristina Rojas, Joel Roca-Martínez, María José Ojeda-Montes, Raúl Beltrán-Debón, Santiago Garcia-Vallve, Gerard Pujadas, Lluís Arola, Miquel Mulero
SCOPE: Resveratrol (RSV) has been described as a potent antioxidant, anti-steatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we tested the combined effect of QCT and RSV on the autophagy process in HepG2 cells METHODS AND RESULTS: Autophagy was studied by western blotting, real-time RT-PCR, and cellular staining...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29333383/inhibitory-effects-of-butein-on-adipogenesis-through-upregulation-of-the-nrf2-ho-1-pathway-in-3t3-l1-adipocytes
#7
Jinwoo Yang, Jeehye Sung, Younghwa Kim, Heon Sang Jeong, Junsoo Lee
Butein is reported to have many biological effects, including anti-fibrogenic, anti-cancer, and anti-inflammatory activities. This study investigated the effects of butein on adipocyte differentiation and the Nrf2/heme oxygenase-1 (HO-1) pathway's involvement in its anti adipogenic mechanism. Butein treatment reduced protein expression of key adipogenic transcription factors such as CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). At a concentration of 5, 10, and 25 μM butein, PPARγ was decreased by 78...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#8
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29329615/synthesis-and-cytotoxicity-evaluation-of-3-amino-2-hydroxypropoxygenistein-derivatives
#9
Xiao-Ting Geng, Jing-Jing Tang, Kun-Peng Cheng, Yuan-Tao Fu, Rong Hu, Jin-Rong Lu
Soy isoflavones exhibit various biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardiovascular protective effects. The present study was designed to investigate the effects of sixteen synthesized 3-amino-2-hydroxypropoxy genistein derivatives on cell proliferation and activation of Nrf2 (Nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response elements) pathway in human cancer cell lines. Most of the tested compounds exerted greater cytotoxic activity than genistein, as measured by MTT assay...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329609/garcinia-xanthochymus-extract-protects-pc12-cells-from-h2o2-induced-apoptosis-through-modulation-of-pi3k-akt-and-nrf2-ho-1-pathways
#10
Jing Xu, Sheng Gan, Jun Li, De-Bing Wand, Yu Chen, Xin Hu, Guang-Zhong Yang
The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against H2O2-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc fraction (fruit-EFr., 12.5-50 µmol·L-1) of G. xanthochymus for 24 h prior to H2O2 exposure markedly improved cell viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases (MMP), and scavenged reactive oxygen species (ROS)...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29328478/arctigenin-exerts-protective-effects-against-myocardial-infarction-via-regulation-of-inos-cox%C3%A2-2-erk1-2-and-ho%C3%A2-1-in-rats
#11
Yanmin Zhang, Yong Yang
The present study aimed to determine the protective effects of arctigenin against myocardial infarction (MI), and its effects on oxidative stress and inflammation in rats. Left anterior coronary arteries of Sprague‑Dawley rats were ligated, in order to generate an acute MI (AMI) model. Arctigenin was administered to AMI rats at 0, 50, 100 or 200 µmol/kg. Western blotting and ELISAs were performed to analyze protein expression and enzyme activity. Arctigenin was demonstrated to effectively inhibit the levels of alanine transaminase, creatine kinase‑MB and lactate dehydrogenase, and to reduce infarct size in AMI rats...
January 10, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328470/cobalt-protoporphyrin-enhances-heme-oxygenase-1-expression-and-attenuates-liver-ischemia-reperfusion-injury-by-inhibiting-apoptosis
#12
Jing Li, Bin Wu, Dahong Teng, Xiaoye Sun, Junjie Li, Jiang Li, Guoliang Zhang, Jinzhen Cai
The aim of the present study was to investigate the preconditioning effect and underlying mechanisms of cobalt-protoporphyrin (CoPP) in a mouse model of liver ischemia‑reperfusion (I/R) injury. Mice were divided into five groups: Sham‑operated (control), I/R, I/R + CoPP, I/R + CoPP and zinc‑protoporphyrin (ZnPP) and I/R + ZnPP. Serum levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) were detected using commercial kits. The expression of the pro‑apoptotic protein caspase‑3 was detected by immunohistochemistry and the expression levels of the anti‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) and heme oxygenase 1 (HO‑1) were analyzed by western blotting...
January 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328408/genistein-attenuates-di%C3%A2-2%C3%A2-ethylhexyl-phthalate-induced-testicular-injuries-via-activation-of-nrf2-ho%C3%A2-1-following-prepubertal-exposure
#13
Liandong Zhang, Hecheng Li, Ming Gao, Tongdian Zhang, Zhizhong Wu, Ziming Wang, Tie Chong
Di‑(2‑ethylhexyl) phthalate (DEHP) and genistein (GEN) are of the most common endocrine disrupting chemicals (EDCs) present in the environment or the diet. However, investigation of the effects of acute exposure to these two EDCs during prepuberty has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague‑Dawley rats by gavage from PND22 to PND35 with vehicle control, GEN 50 mg/kg body weight (bw)/day, DEHP50, 150 and 450 mg/kg bw/day, and combined treatment. Reproductive parameters including testis weight, anogenital distance and organ coefficient were evaluated on PND36...
January 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29326403/resveratrol-an-nrf2-activator-ameliorates-aging-related-progressive-renal-injury
#14
Eun Nim Kim, Ji Hee Lim, Min Young Kim, Tae Hyun Ban, In-Ae Jang, Hye Eun Yoon, Cheol Whee Park, Yoon Sik Chang, Bum Soon Choi
BACKGROUND: Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. METHODS: Male 18-month-old C57BL/6 mice were used...
January 11, 2018: Aging
https://www.readbyqxmd.com/read/29319901/gomisin-a-modulates-aging-progress-via-mitochondrial-biogenesis-in-human-diploid-fibroblast-cells
#15
Jeong-Seok Kim, Seon-Hwa Jeong, Sin-Hee Han, Ho-Keun Yi
Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative stress. However, the potential benefit of gomisin A is still not well understood, especially in aging progression. Therefore, the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti-aging progression, and its mechanism. Intermediate (PD32) Human diploid fibroblast (HDF) cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide (H2 O2 )...
January 10, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29317217/crucial-role-of-ho-1-irf4-dependent-apoptosis-induced-by-panobinostat-and-lenalidomide-in-multiple-myeloma
#16
Sishi Tang, Dan Ma, Bingqing Cheng, Qing Fang, Xinyi Kuang, Kunling Yu, Weili Wang, Bo Hu, Jishi Wang
Inhibition of histone deacetylase (HDAC) is a promising therapeutic strategy for various hematologic cancers. Panobinostat has been approved for treating patients with multiple myeloma (MM) by the FDA. Since the mechanism for the resistance of panobinostat to MM remains elusive, we aimed to clarify this mechanism and the synergism of panobinostat with lenalidomide. The mRNA and protein of transcription factor IRF4 were overexpressed in CD138+ mononuclear cells from MM patients compared with in those from healthy donors...
January 6, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29316751/-mechanism-of-action-for-oligomeric-proanthocyaniclins-in-pava-qnat-induced-acute-lung-injury
#17
P Liu, Y S Zhou, Y L Qin, L Li, Y Liu, B Xu, K Huang, C C Ji, F Lin, Y G Wang, K Li, S H Chen, L F Shao, J S Mu
Objective: The present study was designed to evaluate the protective effects of oligomeric proanthocyanidins (OPC) in mice exposed to paraquat (PQ) , and to explore the molecular mechanism. Methods: Four experimental groups were designed. CONTROL GROUP: 10 BALB/c mice were intraperitoneally injected with normal saline) . PQ group: 10 BALB/c mice were intraperitoneally injected with PQ (100 mg/kg) . PQ+OPC group: 10 BALB/c mice were administered with OPC (100 mg/kg) for 1 h before PQ (100 mg/kg) expo-sure...
November 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29316264/heme-oxygenase-1-affects-generation-and-spontaneous-cardiac-differentiation-of-induced-pluripotent-stem-cells
#18
Jacek Stepniewski, Tomasz Pacholczak, Aniela Skrzypczyk, Maciej Ciesla, Agata Szade, Krzysztof Szade, Romain Bidanel, Agnieszka Langrzyk, Radoslaw Grochowski, Felix Vandermeeren, Neli Kachamakova-Trojanowska, Mateusz Jez, Grazyna Drabik, Mahito Nakanishi, Alicja Jozkowicz, Jozef Dulak
Cellular stress can influence efficiency of iPSCs generation and their differentiation. However, the role of intracellular cytoprotective factors in these processes is still not well known. Therefore, we investigated the effect of HO-1 (Hmox1) or Nrf2 (Nfe2l2), two major cytoprotective genes. Hmox1-/- fibroblasts demonstrated decreased reprogramming efficiency in comparison to Hmox1+/+ cells. Reversely, pharmacological enhancement of HO-1 resulted in higher number of iPSCs colonies. Importantly, elevated level of both p53 and p53-regulated miR-34a and 14-3-3σ was observed in HO-1-deficient fibroblasts whereas downregulation of p53 in these cells markedly increased their reprogramming efficiency...
January 9, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29311669/adipocyte-activated-oxidative-and-er-stress-pathways-promote-tumor-survival-in-bone-via-upregulation-of-heme-oxygenase-1-and-survivin
#19
Mackenzie K Herroon, Erandi Rajagurubandara, Jonathan D Diedrich, Elisabeth I Heath, Izabela Podgorski
Metastatic tumor cells engage the local tumor microenvironment and activate specific pro-survival mechanisms to thrive and progress in the harsh bone marrow niche. Here we show that the major contributors to the survival of carcinoma cells that have colonized the bone marrow are the adipocyte-induced oxidative stress and ER stress pathways. We demonstrate that upon exposure to adipocyte-rich environments in vitro or in vivo, bone-trophic prostate and breast tumor cells upregulate the oxidative stress enzyme, HO-1...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311246/candida-albicans-%C3%AE-glucan-containing-particles-increase-ho-1-expression-in-oral-keratinocytes-via-ros-p38mapk-nrf2-pathway
#20
Yoko Ishida, Kouji Ohta, Takako Naruse, Hiroki Kato, Akiko Fukui, Hideo Shigeishi, Hiromi Nishi, Kei Tobiume, Masaaki Takechi
Oral keratinocytes provide the first line of host defense against oral candidiasis. We speculated that interactions of fungal cell wall components with oral keratinocytes regulate stress response against Candida infection, and examined the expression of genes induced by heat-killed Candida albicans in oral immortalized keratinocytes using a cDNA microarray technique. Of 24,000 genes revealed by that analysis, we focused on HO-1, a stress-inducible gene, as its expression was increased by both heat-killed as well as live C...
January 8, 2018: Infection and Immunity
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