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https://www.readbyqxmd.com/read/28969571/synthesis-%C3%AE-catenin-translocation-capability-and-alp-activation-activity-of-7h-thiazolo-3-2-b-1-2-4-triazin-7-one-derivatives
#1
Shicheng Hou, Henan Xu, Jianshu Hu, Jian Hou, Yan Wang, Zhe Jin, David C C Wan, Chun Hu
Background Osteoporosis (OP) is a common bone disease, most often diagnosed in post-menopausal women. The majority of OP treatments focused at manipulation of the patient's hormone levels, therefore, they are associated with significant adverse effects. Objective To design, synthesize and evaluate the β-catenin translocation capability and the alkaline phosphatase (ALP) activation activity of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. Method The styrene derivatives were synthesized as raw materials, followed by oxidation and condensation reactions, 6-aryl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives (1) were obtained...
October 2, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28951243/root-bark-extracts-of-myrianthus-arboreus-p-beauv-cecropiaceae-exhibit-anti-diabetic-potential-by-modulating-hepatocyte-glucose-homeostasis
#2
Pierre B Kasangana, Abir Nachar, Hoda M Eid, Tatjana Stevanovic, Pierre S Haddad
ETHNOPHARMACOLOGICAL RELEVANCE: Myrianthus arboreus P. Beauv. is a tropical tree used in African folk medicine, including for diabetes. However, little research has yet been conducted to support this ethnopharmacological use of this plant. The present study sought to determine the antidiabetic potential of root bark extracts through cell-based bioassays of liver and muscle glucose homeostasis. MATERIALS AND METHODS: Four extracts were obtained from crude root bark powder: 1 aqueous (AQ), 2 ethanol (EtOH), 3 alkaloid enriched (Alk) (obtained from methanol extract) and 4 dichloromethane (Dic) extracts...
September 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28941685/gsk-3-mediates-no-cgmp-induced-isoflavone-production-in-soybean-sprouts
#3
Caifeng Jiao, Liangliang Zhu, Zhenxin Gu
The role of glycogen synthase kinase-3 (GSK-3) in the nitric oxide-guanosine 3',5'-cyclic monophosphate (NO-cGMP)-induced isoflavone production in soybean sprouts was examined. Inhibitors and donors of NO, cGMP, and GSK-3 inhibitor were added to UV-B irradiated sprouts. Results showed that NO, with cGMP, induced the expression of GSK-3 under UV-B radiation. Protein kinase G (PKG) was shown to be involved in NO-cGMP-induced GSK-3 activation. GSK-3 elevated activity and expression levels of chalcone synthase (CHS) and isoflavone synthase (IFS), and increased isoflavone accumulation...
November 2017: Food Research International
https://www.readbyqxmd.com/read/28933316/photo-activatable-akt-probe-a-new-tool-to-study-the-akt-dependent-physiopathology-of-cancer-cells
#4
Sanae Haga, Takeaki Ozawa, Naoki Morita, Mami Asano, Shigeki Jin, Michitaka Ozakia
Akt is commonly overexpressed and activated in cancer cells, and plays a pivotal role in cell survival, protection andchemo-resistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anti-cancer drugs. Here, we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic-helix-loop-helix (CIB1), can regulate Akt-associated cell functions...
August 30, 2017: Oncology Research
https://www.readbyqxmd.com/read/28930531/isolongifolene-attenuates-rotenone-induced-mitochondrial-dysfunction-oxidative-stress-and-apoptosis
#5
Rengasamy Balakrishnan, Namasivayam Elangovan, Thangavel Mohankumar, Jegadeesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Mohammed Akbar, Mohammed Abdul Sattar Khan
The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28930226/shenlinglan-influences-the-attachment-and-migration-of-ovarian-cancer-cells-potentially-through-the-gsk3-pathway
#6
Sioned Owen, Fiona Ruge, Yunong Gao, Ying Yang, Jianqing Hou, Jian Chen, Yi Feng, Huiming Zhang, Yong Gao, Hongtao Wang, Cong Wei, Yiling Wu, Wen G Jiang
Background: Ovarian cancer presents a major clinical challenge in the UK. Glycogen synthase kinase-3 (GSK-3) has been linked to cancer. This study tested the impact of ShenLingLan (SLDM) on ovarian cancer cell behaviour and its links to GSK-3. Methods: Fresh ovarian tumours (n = 52) were collected and processed. Histopathologcial and clinical information were collected and analysed against GSK-3 transcript levels using quantitative PCR (qPCR). Immortalised ovarian cancer cells' protein alterations in response to SLDM were identified using a Kinexus™ protein kinase array...
February 21, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28916781/6-bromo-indirubin-3-oxime-6bio-a-glycogen-synthase-kinase-3%C3%AE-inhibitor-activates-cytoprotective-cellular-modules-and-suppresses-cellular-senescence-mediated-biomolecular-damage-in-human-fibroblasts
#7
Aimilia D Sklirou, Nicolas Gaboriaud-Kolar, Issidora Papassideri, Alexios-Leandros Skaltsounis, Ioannis P Trougakos
As genetic interventions or extended caloric restriction cannot be applied in humans, many studies have been devoted to the identification of natural products that can prolong healthspan. 6-bromoindirubin-3'-oxime (6BIO), a hemi-synthetic derivative of indirubins found in edible mollusks and plants, is a potent inhibitor of Glycogen synthase kinase 3β (Gsk-3β). This pleiotropic kinase has been implicated in various age-related diseases including tumorigenesis, neurodegeneration and diabetes. Accordingly, 6BIO has shown anti-tumor and anti-neurodegenerative activities; nevertheless, the potential role of 6BIO in normal human cells senescence remains largely unknown...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916722/phosphoproteomics-reveals-that-glycogen-synthase-kinase-3-phosphorylates-multiple-splicing-factors-and-is-associated-with-alternative-splicing
#8
Mansi Y Shinde, Simone Sidoli, Katarzyna Kulej, Michael J Mallory, Caleb M Radens, Amanda Reicherter, Rebecca L Myers, Yoseph Barash, Kristen W Lynch, Benjamin A Garcia, Peter S Klein
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif (pS/pTXXXS/T), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry (MS) techniques to analyze the repertoire of GSK-3-dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ~2...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28887744/microrna-203-suppresses-proliferation-in-liver-cancer-associated-with-pik3ca-p38-mapk-c-jun-and-gsk3-signaling
#9
Annie Zhang, Jaganathan Lakshmanan, Amirreza Motameni, Brian G Harbrecht
Primary liver cancer (hepatocellular carcinoma, HCC) is a leading cause of cancer-related deaths, and alternative ways to treat this disease are urgently needed. In recent years, novel approaches to cancer treatment have been based on microRNAs, small non-coding RNA molecules that play a crucial role in cancer progression by regulating gene expression. Overexpression of some microRNAs has shown therapeutic potential, but whether or not this was the case for microRNA-203 (miR-203) in liver cancer was unknown...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28885630/from-direct-to-indirect-lithium-targets-a-comprehensive-review-of-omics-data
#10
REVIEW
Magali Roux, Anthony Dosseto
Metal ions are critical to a wide range of biological processes. Among them, lithium (Li) has been recognised for its benefit as a treatment for bipolar disorder (BD). However, we are yet to grasp the extent of its role in biological processes, despite its molecular targets having been extensively studied. Here we review a wide range of transcriptomic, proteomic and metabolomic studies in order to obtain a full picture of Li effects at various levels. Multifarious patterns of Li-regulated genes, proteins and metabolites are identified...
October 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28881794/enhanced-efficacy-of-akt-and-fak-kinase-combined-inhibition-in-squamous-cell-lung-carcinomas-with-stable-reduction-in-pten
#11
Andrea Cavazzoni, Silvia La Monica, Roberta Alfieri, Andrea Ravelli, Nele Van Der Steen, Rocco Sciarrillo, Denise Madeddu, Costanza Anna Maria Lagrasta, Federico Quaini, Mara Bonelli, Claudia Fumarola, Daniele Cretella, Graziana Digiacomo, Marcello Tiseo, Godefridus J Peters, Andrea Ardizzoni, Pier Giorgio Petronini, Elisa Giovannetti
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28868937/ameliorative-effect-of-nicotine-exposure-on-insulin-resistance-is-accompanied-by-decreased-cardiac-glycogen-synthase-kinase-3-and-plasminogen-activator-inhibitor-1-during-oral-oestrogen-progestin-therapy
#12
Olugbenga S Michael, Lawrence A Olatunji
CONTEXT: Cigarette smoking is considered to be a major risk factor for the development of diabetes and cardiovascular disease. Oestrogen-progestin combined oral contraceptive (COC) use has been associated with adverse cardiometabolic events. OBJECTIVE: We hypothesized that nicotine would ameliorate insulin resistance (IR) that is accompanied by decreased cardiac glycogen synthase kinase-3 (GSK-3) and plasminogen activator inhibitor-1 (PAI-1). METHODS: Female Wistar rats received (po) low-(0...
September 3, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28828584/neurons-with-multiple-axons-have-functional-axon-initial-segments
#13
Yu Guo, Zhuo Liu, Yi-Kun Chen, Zhen Chai, Chen Zhou, Yan Zhang
Neurons grow multiple axons after treatment with glycogen synthase kinase-3 (GSK-3) inhibitors. However, whether they are electrically active is not known. Here, we examined the role of multiple axons as electrophysiological components during neuronal firing. Combining pharmacological, immunofluorescence, and electrophysiological methods, we found that more neurons had multiple axon initial segments (AISs) after inhibition of GSK-3 activity with SB415286. The multiple AISs induced by GSK-3 inhibition were enriched with voltage-gated sodium channels...
August 21, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28822958/therapeutic-molecules-against-type-2-diabetes-what-we-have-and-what-are-we-expecting
#14
REVIEW
Ashwini Kumar, Sudhanshu Kumar Bharti, Awanish Kumar
World Health Organization (WHO) has identified diabetes as one of the fastest growing non-communicable diseases with 422 million patients around the world in 2014. Diabetes, a metabolic disease, is characterized primarily by hyperglycemia which results in various macrovascular and microvascular complications like cardiovascular disease and neuropathies which can significantly deteriorate the quality of life. The body either does not manufactures enough insulin (type 1 diabetes or T1DM) or becomes insensitive to physiologically secreted insulin or both (type 2 diabetes or T2DM)...
April 9, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28796175/suppression-of-wnt-signaling-and-osteogenic-changes-in-vascular-smooth-muscle-cells-by-eicosapentaenoic-acid
#15
Yukihiro Saito, Kazufumi Nakamura, Daiji Miura, Kei Yunoki, Toru Miyoshi, Masashi Yoshida, Norifumi Kawakita, Tomonari Kimura, Megumi Kondo, Toshihiro Sarashina, Satoshi Akagi, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Morita, Hiroshi Ito
Vascular medial calcification is often observed in patients with arteriosclerosis. It is also associated with systolic hypertension, wide pulse pressure, and fluctuation of blood pressure, which results in cardiovascular events. Eicosapentaenoic acid (EPA) has been shown to suppress vascular calcification in previous animal experiments. We investigated the inhibitory effects of EPA on Wnt signaling, which is one of the important signaling pathways involved in vascular calcification. Intake of food containing 5% EPA resulted in upregulation of the mRNA expression of Klotho, an intrinsic inhibitor of Wnt signaling, in the kidneys of wild-type mice...
August 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28790065/gsk3-inhibition-drives-maturation-of-nk-cells-and-enhances-their-antitumor-activity
#16
Frank Cichocki, Bahram Valamehr, Ryan Bjordahl, Bin Zhang, Betsy Rezner, Paul Rogers, Svetlana Gaidarova, Stacey Moreno, Katie Tuininga, Phillip Dougherty, Valarie McCullar, Peter Howard, Dhifaf Sarhan, Emily Taras, Heinrich Schlums, Stewart Abbot, Daniel Shoemaker, Yenan T Bryceson, Bruce R Blazar, Scott Wolchko, Sarah Cooley, Jeffrey S Miller
Maturation of human natural killer (NK) cells as defined by accumulation of cell-surface expression of CD57 is associated with increased cytotoxic character and TNF and IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57(+) NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacologic inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL15 greatly enhances CD57 upregulation and late-stage maturation...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28772260/microrna-27a-promotes-the-proliferation-and-invasiveness-of-colon-cancer-cells-by-targeting-sfrp1-through-the-wnt-%C3%AE-catenin-signaling-pathway
#17
Sang Ba, Yi Xuan, Zi-Wen Long, Hai-Yong Chen, Shu-Sen Zheng
OBJECTIVE: This study aims to explore the effects of microRNA-27a (miR-27a) on the proliferation and invasiveness of colon cancer cells through the Secreted Frizzled-related protein 1 (SFRP1) and the Wnt/β-catenin signaling pathway. METHODS: Colon cancer tissues and adjacent normal tissues from 125 colon cancer patients, together with the HCEpic, HCT-116, HT-29, SW480 and SW620 cell lines, were prepared for this study. The transfected HCT-116 cells were divided into the miR-27a mimics, miR-27a-NC, anti-miR-27a, blank, Lv-SFRP1, Lv-NC, and miR-27a mimics + Lv-SFRP1 groups...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28761071/phosphopredict-a-bioinformatics-tool-for-prediction-of-human-kinase-specific-phosphorylation-substrates-and-sites-by-integrating-heterogeneous-feature-selection
#18
Jiangning Song, Huilin Wang, Jiawei Wang, André Leier, Tatiana Marquez-Lago, Bingjiao Yang, Ziding Zhang, Tatsuya Akutsu, Geoffrey I Webb, Roger J Daly
Protein phosphorylation is a major form of post-translational modification (PTM) that regulates diverse cellular processes. In silico methods for phosphorylation site prediction can provide a useful and complementary strategy for complete phosphoproteome annotation. Here, we present a novel bioinformatics tool, PhosphoPredict, that combines protein sequence and functional features to predict kinase-specific substrates and their associated phosphorylation sites for 12 human kinases and kinase families, including ATM, CDKs, GSK-3, MAPKs, PKA, PKB, PKC, and SRC...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747658/a-single-amino-acid-substitution-confers-b-cell-clonogenic-activity-to-the-hiv-1-matrix-protein-p17
#19
Cinzia Giagulli, Pasqualina D'Ursi, Wangxiao He, Simone Zorzan, Francesca Caccuri, Kristen Varney, Alessandro Orro, Stefania Marsico, Benoît Otjacques, Carlo Laudanna, Luciano Milanesi, Riccardo Dolcetti, Simona Fiorentini, Wuyuan Lu, Arnaldo Caruso
Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738501/inhibition-of-glycogen-synthase-kinase-3-increased-subventricular-zone-stem-cells-proliferation
#20
Narges Pachenari, Sahar Kiani, Mohammad Javan
The effects of Wnt signaling modifiers on cell proliferation, seem to be cell specific. Enhancing the proliferation of subventricular zone (SVZ) progenitors has been in the focus of research in recent years. Here we investigate the effect of CHIR99021, a Glycogen Synthase Kinase 3 (GSk-3) inhibitor, on SVZ progenitor's proliferation both in vivo and in vitro. Neural stem cells were extracted from the adult C57bl/6 by mincing and trypsin treatment followed by culturing in specific medium. Sphere cells formed within about 7-10days and were characterized by immunostaining...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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