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https://www.readbyqxmd.com/read/29149650/iron-chelation-therapy-in-lower-ipss-risk-myelodysplastic-syndromes-which-subtypes-benefit
#1
Shannon A Wong, Heather A Leitch
BACKGROUND: Analyses suggest MDS patients with higher serum ferritin levels (SF) have inferior overall survival (OS), in one study across MDS subtypes. Multiple analyses suggest those with high SF receiving iron chelation therapy (ICT) have superior OS, but which MDS subtypes benefit from ICT remains undefined. METHODS: We performed survival analyses of MDS subtypes by receipt of ICT. RESULTS: 182 MDS were lower IPSS risk and received red blood cell (RBC) transfusions; 63 received ICT...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29149616/protective-effects-of-proanthocyanidins-against-cadmium-induced-testicular-injury-through-the-modification-of-nrf2-keap1-signal-path-in-rats
#2
Liu He, Peng Li, Li-Hui Yu, Lin Li, Yi Zhang, Yang Guo, Miao Long, Jian-Bin He, Shu-Hua Yang
The purpose of this study was to evaluate the potential chemoprotective effects of proanthocyanidins (PAs) against cadmium (Cd)-induced oxidative damage of testes via Nrf2-Keap1 signal pathway in rats. Briefly, by using biochemical histological analysis, as well as the real time PCR and western blot approach, oxidative damage in rat testicular tissue was observed after exposure to Cd. In addition, significant down-regulations of mRNA and protein levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), γ-glutamyl cysteine synthetase (γ-GCS), glutathione peroxidase (GSH-Px) and quinone oxidoreductase 1 (NQO1), as well as a significant up-regulation of Kelch sample related protein-1 (Keap1) levels in testicular tissue were observed after Cd exposure...
November 3, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29149604/nrf1-is-an-er-membrane-sensor-that-is-central-to-cholesterol-homeostasis
#3
Scott B Widenmaier, Nicole A Snyder, Truc B Nguyen, Alessandro Arduini, Grace Y Lee, Ana Paula Arruda, Jani Saksi, Alexander Bartelt, Gökhan S Hotamisligil
Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29148590/effects-of-bergenin-on-methylglyoxal-induced-damage-in-osteoblastic-mc3t3-e1-cells
#4
Kyung Hee Lee, Eun Mi Choi
Bergenin is the main chemical constituent of plants in the genus Bergenia, which are used in traditional medicines. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is the major precursor for forming advanced glycation end products (AGEs). Pretreating MC3T3-E1 cells with bergenin prevented MG-induced protein adduct formation. Bergenin inhibited the MG-induced soluble receptor for AGE (sRAGE), interleukin, reactive oxygen species and mitochondrial superoxide production. Additionally bergenin increased glyoxalase I activity, glutathione, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 levels in the presence of MG...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29146882/physiological-srsf2-p95h-expression-causes-impaired-hematopoietic-stem-cell-functions-and-aberrant-rna-splicing-in-mice
#5
Ayana Kon, Satoshi Yamazaki, Yasuhito Nannya, Keisuke Kataoka, Yasunori Ota, Masahiro Marshall Nakagawa, Kenichi Yoshida, Yusuke Shiozawa, Maiko Morita, Tetsuichi Yoshizato, Masashi Sanada, Manabu Nakayama, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
Splicing factor (SF) mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not fully been elucidated. Here, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre-mediated conditional knock-in mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplant settings...
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29145840/blockade-of-nicotine-sensitization-by-methanol-extracts-of-glycyrrhizae-radix-mediated-via-antagonism-of-accumbal-oxidative-stress
#6
Zheng Lin Zhao, Sang Chan Kim, Hong Feng Liu, Yi Yan Wu, Li Bo Li, Yu Hua Wang, Yu Jiao, Yu Fan, Chul Won Lee, Bong Hyeo Lee, Il Je Cho, Chae Ha Yang, Rong Jie Zhao
BACKGROUND: We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamine-induced locomotor sensitization and conditioned place preference in rats. In the present study, the effects of MEGR on repeated nicotine-induced locomotor sensitization and enhanced extracellular dopamine (DA) release in the nucleus accumbens (Nacc) were evaluated. METHODS: Male Sprague-Dawley rats received repeated administrations of nicotine (0.4 mg/kg, subcutaneous) or saline twice a day for 7 d and were challenged with nicotine 4 d after the last daily dosing...
November 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29145148/honokiol-protects-pancreatic-%C3%AE-cell-against-high-glucose-and-intermittent-hypoxia-induced-injury-by-activating-nrf2-are-pathway-in-vitro-and-in-vivo
#7
Chen-Guang Li, Chang-Lin Ni, Min Yang, Yun-Zhao Tang, Zhu Li, Yan-Juan Zhu, Zhen-Huan Jiang, Bei Sun, Chun-Jun Li
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29144408/antioxidant-effect-of-barley-sprout-extract-via-enhancement-of-nuclear-factor-erythroid-2-related-factor-2-activity-and-glutathione-synthesis
#8
Yun-Hee Lee, Sou Hyun Kim, Seunghyun Lee, Kyung-Mi Kim, Jae-Chul Jung, Tae Gen Son, Sung Hwan Ki, Woo-Duck Seo, Jae-Hwan Kwak, Jin Tae Hong, Young-Suk Jung
We previously showed that barley sprout extract (BSE) prevents chronic alcohol intake-induced liver injury in mice. BSE notably inhibited glutathione (GSH) depletion and increased inflammatory responses, revealing its mechanism of preventing alcohol-induced liver injury. In the present study we investigated whether the antioxidant effect of BSE involves enhancing nuclear factor-erythroid 2 related factor 2 (Nrf2) activity and GSH synthesis to inhibit alcohol-induced oxidative liver injury. Mice fed alcohol for four weeks exhibited significantly increased oxidative stress, evidenced by increased malondialdehyde (MDA) level and 4-hydroxynonenal (4-HNE) immunostaining in the liver, whereas treatment with BSE (100 mg/kg) prevented these effects...
November 16, 2017: Nutrients
https://www.readbyqxmd.com/read/29141573/liver-protective-effects-of-extra-virgin-olive-oil-interaction-between-its-chemical-composition-and-the-cell-signaling-pathways-involved-in-protection
#9
Sandra A Soto-Alarcon, Rodrigo Valenzuela, Alfonso Valenzuela, Luis A Videla
BACKGROUND AND OBJECTIVE: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage...
November 14, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29140578/alleviation-of-cadmium-induced-oxidative-stress-by-trehalose-via-inhibiting-the-nrf2-keap1-signaling-pathway-in-primary-rat-proximal-tubular-cells
#10
Xin-Yu Wang, Zhen-Yong Wang, Yi-Song Zhu, Si-Ming Zhu, Rui-Feng Fan, Lin Wang
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)-induced oxidative stress via Nrf2 antioxidant pathway. Data showed that Tre treatment inhibited Nrf2 nuclear translocation and restored the decline in Kelch-like ECH-associated protein 1 (Keap1) protein level in Cd-exposed rPT cells. Moreover, Cd-activated Nrf2 target genes, including phase II detoxifying enzymes, that is, NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1, direct antioxidant proteins, that is, glutathione peroxidase, superoxide dismutase, catalase, and glutathione biosynthesis-related proteins, that is, glutamatecysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione reductase, were all downregulated by co-treatment with Tre...
November 15, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29139060/iron-metabolism-in-erythroid-cells-and-patients-with-congenital-sideroblastic-anemia
#11
REVIEW
Kazumichi Furuyama, Kiriko Kaneko
Sideroblastic anemias are anemic disorders characterized by the presence of ring sideroblasts in a patient's bone marrow. These disorders are typically divided into two types, congenital or acquired sideroblastic anemia. Recently, several genes were reported as responsible for congenital sideroblastic anemia; however, the relationship between the function of the gene products and ring sideroblasts is largely unclear. In this review article, we will focus on the iron metabolism in erythroid cells as well as in patients with congenital sideroblastic anemia...
November 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29138829/resveratrol-ameliorates-inflammatory-damage-and-protects-against-osteoarthritis-in-a-rat-model-of-osteoarthritis
#12
Yulong Wei, Jie Jia, Xin Jin, Wei Tong, Hongtao Tian
Resveratrol is a non‑flavonoid polyphenol compound with a stilbene structure. As a type of phytoalexin produced under stress in plants, it improves the plant's resistance against pathogens and environment deterioration, and performs important functions beneficial to human health, such as anti‑cancer, anti‑oxidation, regulating blood lipid levels and prolonging life span. The effects of resveratrol were examined in a rat model of osteoarthritis (OA) and observed to ameliorate inflammatory damage and protect against OA...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138821/protective-effects-of-oxymatrine-against-lipopolysaccharide-d%C3%A2-galactosamine%C3%A2-induced-acute-liver-failure-through-oxidative-damage-via-activation-of-nrf2-ho%C3%A2-1-and-modulation-of-inflammatory-tlr4%C3%A2-signaling-pathways
#13
Jian Xu, Chengmin Li, Ziwei Li, Chan Yang, Lan Lei, Wei Ren, Yan Su, Chunping Chen
Oxymatrine has a variety of pharmacological functions, including anti-viral, anti-liver fibrotic, anti-cancer, anti‑bacterial, anti‑epidemic, analgesic, anti‑allergy and anti‑inflammatory properties. The present study aimed to investigate the protective effects of oxymatrine against lipopolysaccharide (LPS)/D‑galactosamine (D‑GalN)‑induced acute liver failure and the associated underlying mechanisms. Mice were administrated 4 mg/kg LPS and 600 mg/kg D‑GalN. Then, mice in the Oxymatrine group were treated with 120 mg/kg of oxymatrine for 4 weeks...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138814/grape-seed-proanthocyanidin-extract-attenuates-varicocele%C3%A2-induced-testicular-oxidative-injury-in-rats-by-activating-the-nrf2%C3%A2-antioxidant-system
#14
Yong Wang, Fan Chen, Ming Liang, Shouzhen Chen, Yaofeng Zhu, Zhichuan Zou, Benkang Shi
The present study investigated whether grape seed proanthocyanidin extract (GSPE) can attenuate varicocele‑induced testicular oxidative injury through the nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) antioxidant pathway. A varicocele model in rats was established by partial ligation of the left renal vein. Following 4 weeks of GSPE administration, the decreased sperm count and motility and other pathological changes caused by varicocele were significantly alleviated, as indicated by the results of computer‑assisted sperm analysis and hematoxylin and eosin staining...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29137304/monocarboxylate-transporter-1-mct1-a-tool-to-stratify-acute-myeloid-leukemia-aml-patients-and-a-vehicle-to-kill-cancer-cells
#15
Filipa Lopes-Coelho, Carolina Nunes, Sofia Gouveia-Fernandes, Rita Rosas, Fernanda Silva, Paula Gameiro, Tânia Carvalho, Maria Gomes da Silva, José Cabeçadas, Sérgio Dias, Luís G Gonçalves, Jacinta Serpa
Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136768/lipoxin-a4-protects-against-spinal-cord-injury-via-regulating-akt-nuclear-factor-erythroid-derived-2-like-2-heme-oxygenase-1-signaling
#16
Tan Lu, Xuejian Wu, Na Wei, Xiaotan Liu, Yingfeng Zhou, Chunfeng Shang, Yongzhuang Duan, Yuzhen Dong
Spinal cord injury (SCI) is a devastating physical trauma worldwide. The mechanisms of SCI are still not clear and the effective treatment is limited. Lipoxin A4 (LXA4) possesses anti-inflammatory and neuroprotective effects. The present study was designed to further evaluate the molecular mechanisms of LXA4-induced protective effects in a rat model of SCI. We found that LXA4 increased Basso, Beattie and Bresnahan (BBB) scores, increased mechanical paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) to a radiant heat, reduced the lesion volume, decreased Bax mRNA expression and increased Bcl-2 expression after SCI...
November 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#17
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29135282/genome-wide-dna-methylation-drives-human-embryonic-stem-cell-erythropoiesis-by-remodeling-gene-expression-dynamics
#18
Zhijing Liu, Qiang Feng, Pengpeng Sun, Yan Lu, Minlan Yang, Xiaowei Zhang, Xiangshu Jin, Yulin Li, Shi-Jiang Lu, Chengshi Quan
AIM: To investigate the role of DNA methylation during erythrocyte production by human embryonic stem cells (hESCs). METHODS: We employed an erythroid differentiation model from hESCs, and then tracked the genome-wide DNA methylation maps and gene expression patterns through an Infinium HumanMethylation450K BeadChip and an Ilumina Human HT-12 v4 Expression Beadchip, respectively. RESULTS: A negative correlation between DNA methylation and gene expression was substantially enriched during the later differentiation stage and was present in both the promoter and the gene body...
November 14, 2017: Epigenomics
https://www.readbyqxmd.com/read/29132906/a-selective-knockout-method-for-discovery-of-minor-active-components-from-plant-extracts-feasibility-and-challenges-as-illustrated-by-an-application-to-salvia-miltiorrhiza
#19
Xue-Yan Li, Hong-Jin Tang, Liu Zhang, Lin Yang, Ping Li, Jun Chen
Natural products have been recognized to play an invaluable role in drug discovery. However, efficient discovery of minor active constituents from natural sources is challenging due to the low abundance and complex matrices. In this study, we developed a selective knockout method to discover minor bioactive components from complex phytochemical mixtures, using a Chinese medicine as an example. Based on the chromatographic fingerprint, six major components in the ethyl acetate extract of the root of Salvia miltiorrhiza (EASM) were selectively knocked out via high-resolution peak fraction (HRPF) approach...
October 7, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29129772/glycyrrhizin-ameliorates-high-fat-diet-induced-obesity-in-rats-by-activating-nrf2-pathway
#20
Nada F Abo El-Magd, Mohamed El-Mesery, Amro El-Karef, Mamdouh M El-Shishtawy
AIM: Obesity based on insulin resistance is a state of chronic oxidative stress and inflammation that are highly regulated through nuclear factor Erythroid 2-related factor 2 (NrF2) pathway. MATERIALS AND METHODS: 70 male Wistar rats were randomized into two models. The prophylactic model was 10weeks and rats were grouped into: normal group, GL group (received glycyrrhizin 50mg/kg/day orally along with normal pellet diet), HFD group and HFD+ GL group (received glycyrrhizin along with HFD)...
November 9, 2017: Life Sciences
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