Read by QxMD icon Read


N Zhao, L Mi, X J Zhang, M Y Xu, H Y Yu, Z W Liu, X J Liu, G C Guan, W Gao, J K Wang
MicroRNA 711 (miR-711) levels in the heart change dynamically after myocardial infarction (MI). As peroxisome proliferator-activated receptor gamma (PPARγ) can upregulate miR-711 in adipocytes and cardiac fibroblasts, this study examined the precise mechanism of PPARγ-mediated miR-711 upregulation and its role in the heart in the early stages after MI. In a rat model of MI induced by left anterior descending coronary artery ligation, immunohistochemical and western blot analyses revealed increased PPARγ expression in cardiomyocyte nuclei after MI...
March 6, 2018: Journal of Molecular and Cellular Cardiology
Chien-Heng Shen, Shui-Yi Tung, Wen-Shih Huang, Kam-Fai Lee, Yung-Yu Hsieh, Meng Chiao Hsieh, Cheng-Nan Chen, Hsing-Chun Kuo
BACKGROUND/AIMS: Oxidants are important human toxicants. They have been implicated in the occurrence and development of liver diseases. Increased intracellular tert-butylhydroperoxide (t-BHP) may be critical for oxidant toxicity, and is commonly used for evaluating mechanisms involving oxidative stress, but the method remains controversial. METHODS: Primary cultures of hepatocytes as well as human Hep G2 and mouse FL83B liver cells were obtained. Cell viability was measured by annexin V-FITC/propidium iodide and DAPI staining to determine the effects of t-BHP treatment on acute liver injury...
March 2, 2018: Cellular Physiology and Biochemistry
Mariachiara Zuccarini, Patricia Giuliani, Monica Frinchi, Giuseppa Mudò, Rosa Maria Serio, Natale Belluardo, Silvana Buccella, Marzia Carluccio, Daniele F Condorelli, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio
Mounting evidence suggests that the guanine-based purines stand out as key player in cell metabolism and in several models of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. Guanosine (GUO) and guanine (GUA) are extracellular signaling molecules derived from the breakdown of the correspondent nucleotide, GTP, and their intracellular and extracellular levels are regulated by the fine-tuned activity of two major enzymes, purine nucleoside phosphorylase (PNP) and guanine deaminase (GDA)...
2018: Frontiers in Pharmacology
Chen Zhang, Dong Qian, Hongzhi Zhao, Nan Lv, Pei Yu, Zhe Sun
OBJECTIVES: MicroRNAs (miRNAs) are involved in the pathological progression of various disease including type 2 diabetes (T2D). Chronic inflammation in adipose tissue is a cause of insulin resistance and T2D. MiR-17 palys an anti-inflammatory role in many biological processes. We hypothesized that miR-17 suppressed inflammatory macrophage that is related to insulin resistance in patients with T2D. METHODS: Macrophage migration and secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β were detected through transwell migration assay and enzyme-linked immunosorbent assay, respectively...
February 21, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Na Zhang, Xiaojia Liu, Lu Liu, Zhesong Deng, Qingxuan Zeng, Weiqiang Pang, Yang Liu, Danqing Song, Hongbin Deng
Glycogen synthase kinase-3β (GSK-3β) is a ubiquitously expressed serine/threonine kinase involved in a variety of functions ranging from the control of glycogen metabolism to transcriptional regulation. We recently demonstrated that GSK-3β inhibition triggered ASK1-JNK-dependent apoptosis in human hepatocellular carcinoma (HCC) cells. However, the comprehensive picture of downstream GSK-3β-regulated pathways/functions remains elusive. In this study, we showed that GSK-3β was aberrantly activated in HCC...
February 14, 2018: Cell Death & Disease
Gyrid Nygaard, Julie A Di Paolo, Deepa Hammaker, David L Boyle, Grant Budas, Gregory T Notte, Igor Mikaelian, Vivian Barry, Gary S Firestein
Despite improved therapy, rheumatoid arthritis (RA) remains an unmet medical need. Previous efforts to validate therapeutic targets in the mitogen-activated protein kinase (MAPK) family have had minimal success. Therefore, we evaluated the potential for targeting an upstream MAPK, namely apoptosis signal-regulating kinase 1 (ASK1), as an alternative approach. ASK1 protein and gene expression were observed in RA and osteoarthritis (OA) synovium as determined by immunohistochemistry (IHC) and qPCR, respectively, particularly in the synovial intimal lining...
February 2, 2018: Biochemical Pharmacology
Jun Ma, Di Zhao, Hong Lu, Wei Huang, Dahai Yu
Silver nanoparticles (AgNPs) are one of the most important nanomaterials in the field of medicine. Our study investigated whether AgNPs induce apoptosis of human adenocarcinoma A549 cells and their possible involvement in Apoptosis Signal-Regulating Kinase 1 (ASK1). The prepared AgNPs had high stability and excellent monodispersity. They also possessed inhibitory effect on A549 cells proliferation in a concentration-dependent manner by Cell Counting Kit-8 (CCK8) assay and Hoechst 33342 Fluorescence. The AgNPs significantly induced production of reactive oxygen species (ROS) in A549 cells...
March 2017: Journal of Biomedical Nanotechnology
David E Place, Parimal Samir, Rajendra Karki, Benoit Briard, Peter Vogel, Thirumala-Devi Kanneganti
Activation of the multimeric inflammasome complex leads to inflammatory responses to biotic and abiotic triggers. The inflammasome sensor, Nod-like receptor family Pyrin domain containing 3 (NLRP3), is activated by a range of stimuli and is tightly regulated to restrict excessive inflammation. Because NLRP3 responds broadly to cellular insults and regulates cell death similar to the stress-activated apoptosis signal-regulating kinases 1 and 2 (ASK1/2), we hypothesized that ASK1/2 may regulate NLRP3 activity...
January 15, 2018: American Journal of Pathology
Yajun Luo, Cheng Wang, Peng Yong, Pengcheng Ye, Zilin Liu, Zhiming Fu, Fei Lu, Wanping Xiang, Wang Tan, Jiangwei Xiao
Many lncRNA and mRNA sense-antisense transcripts have been systematically identified in malignant cells. However, the molecular mechanisms of most lncRNA-mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer-associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is significantly down-regulated in gastric cancer and could promote tumor growth in vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11 via the ASK1-p38MAPK/JNK signaling pathway...
December 22, 2017: Oncotarget
Frank Lovering, Paul Morgan, Christophe Allais, Ann Aulabaugh, Joanne Brodfuehrer, Jeanne Chang, Jotham Coe, WeiDong Ding, Heather Dowty, Margaret Fleming, Richard Frisbie, Julia Guzova, David Hepworth, Jayasankar Jasti, Steve Kortum, Ravi Kurumbail, Shashi Mohan, Nikolaos Papaioannou, Joseph W Strohbach, Fabien Vincent, Katherine Lee, Christoph W Zapf
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases...
December 15, 2017: European Journal of Medicinal Chemistry
Himanshu Tripathi, Feroz Khan
Identification of hit compounds against specific target form the starting point for a drug discovery program. A consistent decline of new chemical entities (NCEs) in recent years prompted a challenge to explore newer approaches to discover potential hit compounds that in turn can be converted into leads, and ultimately drug with desired therapeutic efficacy. The vast amount of omics and activity data available in public databases offers an opportunity to identify novel targets and their potential inhibitors...
January 1, 2018: Computational Biology and Chemistry
Youyang Qu, Yu Liu, Li Chen, Yanmei Zhu, Xingjun Xiao, Di Wang, Yulan Zhu
Objectives Cadmium (Cd), an extremely noxious environmental pollutant is known to induce oxidative stress leading to neurodegenerative diseases. Nobiletin, a citrus flavonoid is reported to possess various pharmacological properties. This study investigates the effects of nobiletin over Cd-induced neuronal apoptosis in rodent experimental model. Methods To separate group of male Sprague Dawley rats, Cd (2 mL/kg/day) was subcutaneously injected for one month which results in a dose level of 1 mg/kg Cd. Couple of days prior to Cd injection, the treatment group rats regularly received nobiletin (50, 100, or 200 mg/kg b...
January 16, 2018: Neurological Research
Lei Shi, Zaizong Wang, Xianjin Liu, Mao Li, Shangfei Zhang, Xiaobin Song
Background and Purpose Bax inhibitor-1 (BI-1) has been identified as a suppressor of Bax-mediated cell apoptosis by regulation of endoplasmic reticulum stress-induced cell death. However, the role of BI-1 in Early Brain Injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. In the present study, we aim to explore the neuroprotective functions of BI-1 in EBI after SAH by using models of SAH that induced endovascular perforation in rats. Method The neurological score, brain water content and blood-brain barrier (BBB) permeability were evaluated simultaneously as prognostic indicators...
January 16, 2018: Neurological Research
Tianjiao Xu, Chengu Niu, Xiaojie Zhang, Miaoxian Dong
Recently, the significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to the loss of neuroprotective estrogen after menopause. Does phytoestrogen have the ability to protect against amyloid-β (Aβ) toxicity? The aim of this study was to evaluate hypothesis that β-ecdysterone (β-Ecd) protects SH-SY5Y cells from Aβ-induced apoptosis by separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal kinase (JNK). Here, we demonstrate that phytoestrogen β-Ecd inhibits Aβ-triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Daniel Dávila-González, Dong Soon Choi, Roberto R Rosato, Sergio Granados-Principal, John G Kuhn, Wen-Feng Li, Wei Qian, Wen Chen, Anthony J Kozielski, Helen H Wong, Bhuvanesh Dave, Jenny C Chang
PURPOSE: Chemoresistance in triple negative breast cancer (TNBC) is associated with the activation of a survival mechanism orchestrated by the endoplasmic reticulum (EnR) stress response and by inducible nitric oxide synthase (iNOS). Our aim was to determine the effects of pharmacological NOS-inhibition on TNBC. EXPERIMENTAL DESIGN: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS-inibitor (L-NMMA) for 24, 48 and 72 hours...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Wendi Yang, Bing Hui Wang, Ian Wang, Li Huang, Feby Savira, Andrew Kompa, Beat M Jucker, Robert N Willette, Darren Kelly, Henry Krum, Zhiliang Li, Qian Fu
BACKGROUND: Cardiac remodelling is a dynamic process whereby structural and functional changes occur within the heart in response to injury or inflammation. Recent studies have demonstrated reactive oxygen species sensitive MAPK, apoptosis signal-regulating kinase 1 (ASK1) plays a critical role in cardiac remodelling. This study aims to determine the effectiveness of small molecule ASK1 inhibitors on these processes and their therapeutic potential. METHODS: Neonatal rat cardiac fibroblasts (NCF) were pre-treated with ASK1 inhibitors, G2261818A (G226) and G2358939A (G235), for 2hours before stimulated with 100nM angiotensin II (AngII), 10μM indoxyl sulphate (IS) or 10ng/ml transforming growth factor β1 (TGFβ1) for 48hours...
December 14, 2017: Heart, Lung & Circulation
Andrii Monastyrskyi, Simon Bayle, Victor Quereda, Wayne Grant, Michael Cameron, Derek Duckett, William Roush
The development of a new series of apoptosis signal-regulating kinase 1 (ASK1) inhibitors is described. Starting from purine, pyrimidine and quinazoline scaffolds identified by high throughput screening, we used tools of structure-based drug design to develop a series of potent kinase inhibitors, including 2-arylquinazoline derivatives 12 and 23, with submicromolar inhibitory activities against ASK1. Kinetic analysis demonstrated that the 2-arylquinazoline scaffold ASK1 inhibitors described herein are ATP competitive...
December 13, 2017: Bioorganic & Medicinal Chemistry Letters
Dilini N Kekulandara, Shima Nagi, Hyosuk Seo, Christine S Chow, Young-Hoon Ahn
Thioredoxin 1 (Trx1) and glutaredoxin 1 (Grx1) are two ubiquitous redox enzymes that are central for redox homeostasis, but also are implicated in many other processes, including stress sensing, inflammation, and apoptosis. In addition to their enzymatic redox activity, there is increasing evidence showing that Trx1 and Grx1 play regulatory roles via protein-protein interactions with specific proteins, including Ask1. The currently available inhibitors of Trx1 and Grx1 are thiol-reactive electrophiles or disulfides that may suffer from low selectivity due to their thiol reactivity...
December 20, 2017: Biochemistry
Marion Lanier, Jason Pickens, Simone V Bigi, Erica L Bradshaw-Pierce, Alison Chambers, Zacharia S Cheruvallath, Derek Cole, Douglas R Dougan, Jacques Ermolieff, Tony Gibson, Petro Halkowycz, Aki Hirokawa, Anthony Ivetac, Christopher McBride, Joanne Miura, Evan Nunez, Mark Sabat, John Tyhonas, Haixia Wang, Xiaolun Wang, Steve Swann
[This corrects the article DOI: 10.1021/acsmedchemlett.6b00481.].
December 14, 2017: ACS Medicinal Chemistry Letters
Samantha Louise Cooper, Hardip Sandhu, Afthab Hussain, Christopher Mee, Helen Maddock
The tyrosine kinase inhibitor Sunitinib is used to treat cancer and is linked to severe adverse cardiovascular events. Mitogen activated kinase kinase 7 (MKK7) is involved in the development of cardiac injury and is a component of the c-Jun N-terminal kinase (JNK) signal transduction pathway. Apoptosis signal-regulating kinase 1 (ASK1) is the upstream activator of MKK7 and is specifically inhibited by 2,7-dihydro-2,7-dioxo-3H-naphtho[1,2,3-de]quinoline-1-carboxylic acid ethyl ester (NQDI-1). This study investigates the role of ASK1, MKK7 and JNK during Sunitinib-induced cardiotoxicity...
December 14, 2017: Toxicology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"