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https://www.readbyqxmd.com/read/28922779/targeting-the-myofibroblastic-cancer-associated-fibroblast-phenotype-through-inhibition-of-nox4
#1
Christopher J Hanley, Massimiliano Mellone, Kirsty Ford, Steve M Thirdborough, Toby Mellows, Steven J Frampton, David M Smith, Elena Harden, Cedric Szyndralewiez, Marc Bullock, Fergus Noble, Karwan A Moutasim, Emma V King, Pandurangan Vijayanand, Alex H Mirnezami, Timothy J Underwood, Christian H Ottensmeier, Gareth J Thomas
Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#2
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916474/nox4-regulates-the-enos-uncoupling-process-in-aging-endothelial-cells
#3
Hwa-Young Lee, Hyung-Ryong Kim, Han-Jung Chae
ROS and its associated signaling contribute to vascular aging-associated endothelial disturbance. Since the non-effective endothelial nitric oxide synthase (eNOS) coupling status is related to vascular aging-related phenotypes, eNOS coupled/uncoupled system signaling was studied in human umbilical vein endothelial cells (HUVEC). Nitric oxide (NO) and eNOS Ser1177 were significantly decreased, whereas O2(-) (superoxide anion radical) increased with passage number. In aging cells, NADPH oxidase 4 (Nox4), one of the main superoxide generating enzymes, and its associated protein disulfide isomerase (PDI) chaperone were highly activated, and the resultant ER redox imbalance leads to disturbance of protein folding capability, namely endoplasmic reticulum (ER) stress, ultimately inducing dissociation between HSP90 and IRE-1α or PERK, decreasing HSP90 stability and dissociating the binding of eNOS from the HSP90 and leading to eNOS uncoupling...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28912882/atorvastatin-alleviates-iodinated-contrast-media-induced-cytotoxicity-in-human-proximal-renal-tubular-epithelial-cells
#4
Gai-Ling Liu, Rong Lei, Shao-Bin Duan, Mi-Mi Tang, Min Luo, Qian Xu
Contrast media (CM)-induced nephropathy (CIN) is a serious complication of intravascularly applied radiocontrast media. At present, no drugs have been approved for the prevention of CIN. The present study aimed to explore the effects and potential mechanisms of atorvastatin on iodinated CM-induced cytotoxicity in the human proximal renal tubular epithelial cells. The cytotoxic effect of iohexol (50, 100 and 200 mg I/ml) and the protective effect of atorvastatin pretreatment (1, 20 and 40 µM) were assessed...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#5
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28899493/protective-effects-of-paeoniflorin-against-aopp-induced-oxidative-injury-in-huvecs-by-blocking-the-ros-hif-1%C3%AE-vegf-pathway
#6
Shaolian Song, Xiaoyan Xiao, Dan Guo, Liqian Mo, Can Bu, Wenbin Ye, Quanwen Den, Shiting Liu, Xixiao Yang
BACKGROUND: Paeoniflorin, a monoterpene glycoside, exerts protective vascular effects, showing good antioxidant properties. However, whether Paeoniflorin has protective effect against the oxidative damage induced by advanced oxidation protein products (AOPPs) in Human umbilical vein endothelial cells (HUVECs) is unknown, as is the underlying mechanism. PURPOSE: The present study was designed to investigate the effect of Paeoniflorin on oxidative damage of HUVECs and elucidate its underlying molecular mechanisms...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28899085/correlation-between-nadph-oxidase-mediated-oxidative-stress-and-dysfunction-of-endothelial-progenitor-cell-in-hyperlipidemic-patients
#7
Ting-Bo Li, Yin-Zhuang Zhang, Wei-Qi Liu, Jie-Jie Zhang, Jun Peng, Xiu-Ju Luo, Qi-Lin Ma
Background/Aims: NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-mediated oxidative stress plays a key role in promotion of oxidative injury in the cardiovascular system. The aim of this study is to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic patients and to assess the correlation between NOX activity and the functions EPCs. Methods: A total of 30 hyperlipidemic patients were enrolled for this study and 30 age-matched volunteers with normal level of plasma lipids served as controls...
September 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28894215/gene-expression-of-nox-family-members-and-their-clinical-significance-in-hepatocellular-carcinoma
#8
Hyuk Soo Eun, Sang Yeon Cho, Jong Seok Joo, Sun Hyung Kang, Hee Seok Moon, Eaum Seok Lee, Seok Hyun Kim, Byung Seok Lee
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-derived reactive oxygen species (ROS) promote chronic liver inflammation and remodeling that can drive hepatocellular carcinoma development. The role of NOX expression in hepatocellular carcinoma (HCC) has been partially investigated; however, the clinical relevance of collective or individual NOX family member expression for HCC survival remains unclear. Here, we obtained NOX mRNA expression data for 377 HCC samples and 21 normal liver controls from the TCGA data portal and performed Kaplan-Meier survival, gene ontology functional enrichment, and gene set enrichment analyses...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890346/hepatoprotective-effects-of-methyl-ferulic-acid-on-alcohol-induced-liver-oxidative-injury-in-mice-by-inhibiting-the-nox4-ros-mapk-pathway
#9
Chen Li, Li Li, Cheng-Fang Yang, Yu-Juan Zhong, Dan Wu, Lin Shi, Li Chen, Yong-Wen Li
AIMS: The present study aimed to investigate the hepatoprotective effects of Methyl ferulic acid (MFA) against oxidative stress and apoptosis as well as inflammation in mice with liver injury induced by alcohol and its underlying mechanisms. METHODS: C57BL/6 mice were divided into a control group,a model group, and Methyl ferulic acid with high dosage (20 mg/kg), moderate dosage (10 mg/kg) and low dosage (5 mg/kg) groups. The general condition and organ index of each group were investigated...
September 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28874782/dihydrocapsaicin-attenuates-blood-brain-barrier-and-cerebral-damage-in-focal-cerebral-ischemia-reperfusion-via-oxidative-stress-and-inflammatory
#10
Adchara Janyou, Piyawadee Wicha, Jinatta Jittiwat, Apichart Suksamrarn, Chainarong Tocharus, Jiraporn Tocharus
This study investigated the effect of dihydrocapsaicin (DHC) on cerebral and blood brain barrier (BBB) damage in cerebral ischemia and reperfusion (I/R) models. The models were induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. The rats were divided into five groups: sham, or control group; vehicle group; and 2.5 mg/kg, 5 mg/kg, and 10 mg/kg BW DHC-treated I/R groups. After 24 h of reperfusion, we found that DHC significantly reduced the area of infarction, morphology changes in the neuronal cells including apoptotic cell death, and also decreased the BBB damage via reducing Evan Blue leakage, water content, and ultrastructure changes, in addition to increasing the tight junction (TJ) protein expression...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872612/fructus-ligustri-lucidi-in-osteoporosis-a-review-of-its-pharmacology-phytochemistry-pharmacokinetics-and-safety
#11
REVIEW
Beibei Chen, Lili Wang, Lin Li, Ruyuan Zhu, Haixia Liu, Chenyue Liu, Rufeng Ma, Qiangqiang Jia, Dandan Zhao, Jianzhao Niu, Min Fu, Sihua Gao, Dongwei Zhang
Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL...
September 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28867609/ampk-attenuates-ventricular-remodeling-and-dysfunction-following-aortic-banding-in-mice-via-the-sirt3-oxidative-stress-pathway
#12
Yili Chen, Cong Chen, Bin Dong, Fuwei Xing, Huiling Huang, Fengjuan Yao, Yuedong Ma, Jiangui He, Yugang Dong
Although recent findings have suggested that AMP-activated protein kinase (AMPK) exerts inhibitory effects on cardiac remodeling secondary to hypertension, the mechanism and optimal duration of treatment remain unknown. Mice with descending aortic banding (AB) or subjected to sham operation received subcutaneous injection of either AICAR (0.5mg∙g(-1)∙day(-1)) or vehicle over 4 week periods. At the end of 4 week treatment, left ventricular (LV) remodeling and function were evaluated with histological analysis and echocardiography...
August 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28860995/corrigendum-antioxidant-effect-of-fructus-ligustri-lucidi-aqueous-extract-in-ovariectomized-rats-is-mediated-through-nox4-ros-nf-%C3%AE%C2%BAb-pathway
#13
Lili Wang, Rufeng Ma, Yubo Guo, Jing Sun, Haixia Liu, Ruyuan Zhu, Chenyue Liu, Jun Li, Lin Li, Beibei Chen, Liping Sun, Jinfa Tang, Dandan Zhao, Fangfang Mo, Jianzhao Niu, Guangjian Jiang, Min Fu, Dieter Brömme, Dongwei Zhang, Sihua Gao
[This corrects the article on p. 266 in vol. 8, PMID: 28588482.].
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28857948/suppression-of-oxidative-stress-and-apoptosis-in-electrically-stimulated-neonatal-rat-cardiomyocytes-by-resveratrol-and-underlying-mechanisms
#14
Liqi Ge, Zhirong Wang, Chengzong Li, Yao Zhang, Lei Chen
PURPOSE: We explored effects of resveratrol on oxidative stress in cardiomyocytes subjected to rapid electrical stimulation (RES) and also investigated underlying mechanisms. METHODS: Neonatal rat ventricular myocytes cultured were subjected to RES at 4.0 Hz, with or without resveratrol, an NADPH oxidase inhibitor apocyanin (APO) or a Ca/calmodulin dependent protein kinase II (CaMKII) inhibitor autocamtide-2-inhibitory peptide (AIP). Cell counts, to optimize resveratrol concentration, and angiotensin II content were evaluated...
August 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28855398/targeting-the-vascular-and-perivascular-niches-as-a-regenerative-therapy-for-lung-and-liver-fibrosis
#15
Zhongwei Cao, Tinghong Ye, Yue Sun, Gaili Ji, Koji Shido, Yutian Chen, Lin Luo, Feifei Na, Xiaoyan Li, Zhen Huang, Jane L Ko, Vivek Mittal, Lina Qiao, Chong Chen, Fernando J Martinez, Shahin Rafii, Bi-Sen Ding
The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs...
August 30, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28840773/prorenin-receptor-prr-mediated-nadph-oxidase-nox-signaling-regulates-vegf-synthesis-under-hyperglycemic-condition-in-arpe-19-cells
#16
Rashidul Haque, P Michael Iuvone, Li He, Elizabeth H Hur, Kimberly Su Chung Choi, Daniel Park, Annie N Farrell, Ashley Ngo, Samantha Gokhale, Madiha Aseem, Bhavna Kumar
The stimulation of angiotensin II (Ang II), the effector peptide of renin-angiotensin system, has been reported to increase the expression of vascular endothelial growth factor (VEGF) through the activation of the Ang II type 1 receptor (AT1R). In this study, we investigated whether hyperglycemia (HG, 33 mM glucose) in ARPE-19 cells could promote the expression of VEGF independently of Ang II through prorenin receptor (PRR), via an NADPH oxidase (Nox)-dependent mechanism. ARPE-19 cells were treated with the angiotensin converting enzyme (ACE) inhibitor perindopril to block the synthesis of Ang II...
August 25, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28827764/traf4-promotes-lung-cancer-aggressiveness-by-modulating-tumor-microenvironment-in-normal-fibroblasts
#17
EunGi Kim, Wanyeon Kim, Sungmin Lee, Jahyun Chun, JiHoon Kang, Gaeul Park, IkJoon Han, Hee Jung Yang, HyeSook Youn, BuHyun Youn
Normal fibroblasts surrounding tumor cells play a crucial role in cancer progression through formation of the tumor microenvironment. Because factors secreted from normal fibroblasts can modulate the tumor microenvironment, it is necessary to identify key factors associated with regulation of secreted factors and to investigate the molecular mechanisms contributing to the tumor microenvironment formation process. In this study, we found that radiation induced the expression and K63-linkage poly-ubiquitination of TRAF4 in normal lung fibroblasts...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827077/high-potential-defense-mechanisms-of-neocortex-in-a-rat-model-of-transient-asphyxia-induced-cardiac-arrest
#18
Gerburg Keilhoff, Torben Esser, Maximilian Titze, Uwe Ebmeyer, Lorenz Schild
Cardiac arrest (CA) is a common cause of disability and mortality and thus an important risk for human health. Circulatory failure has dramatic consequences for the brain as one of the most oxygen-consuming organs. Hippocampus, striatum and neocortex rate among the most vulnerable brain regions. The neocortex is less sensitive to hypoxia/reperfusion in comparison with the hippocampal CA1 region. That implicates the existence of efficient defense mechanisms in the neocortex against hypoxia/reperfusion injury, which we analyzed in a well-established CA rat model...
August 18, 2017: Brain Research
https://www.readbyqxmd.com/read/28826395/erratum-to-evolutionary-origin-and-function-of-nox4-art-an-arthropod-specific-nadph-oxidase
#19
Ana Caroline Paiva Gandara, André Torres, Ana Cristina Bahia, Pedro L Oliveira, Renata Schama
No abstract text is available yet for this article.
August 21, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28822963/%C3%AE-1a-subtype-adrenergic-agonist-therapy-for-failing-right-ventricle
#20
Patrick M Cowley, Guan-Ying Wang, Sunil K Joshi, Philip M Swigart, David H Lovett, Paul C Simpson, Anthony J Baker
Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α1-adrenergic receptors (α1-ARs), in particular the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies show that chronic treatment with the α1A-subtype agonist A61603 improves function and survival in a model of LV failure. The goal of this study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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