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https://www.readbyqxmd.com/read/28337019/apigenin-induced-lysosomal-degradation-of-%C3%AE-catenin-in-wnt-%C3%AE-catenin-signaling
#1
Chung-Ming Lin, Hsin-Han Chen, Chun-An Lin, Hui-Chung Wu, Jim Jinn-Chyuan Sheu, Hui-Jye Chen
The bioflavonoid apigenin has been shown to possess cancer-preventive and anti-cancer activities. In a drug screening, we found that apigenin can inhibit Wnt/β-catenin signaling, a pathway that participates in pivotal biological functions, which dis-regulation results in various human diseases including cancers. However, the underlying mechanism of apigenin in this pathway and its link to anti-cancer activities remain largely unknown. Here we showed that apigenin reduced the amount of total, cytoplasmic, and nuclear β-catenin, leading to the suppression in the β-catenin/TCF-mediated transcriptional activity, the expression of Wnt target genes, and cell proliferation of Wnt-stimulated P19 cells and Wnt-driven colorectal cancer cells...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332716/mir-124-and-mir-9-mediated-downregulation-of-hdac5-promotes-neurite-development-through-activating-mef2c-gpm6a-pathway
#2
Xi Gu, Congcong Fu, Lifang Lin, Shuhu Liu, Xiaohong Su, Aili Li, Qiaoqi Wu, Chunhong Jia, Peidong Zhang, Lu Chen, Xinhong Zhu, Xuemin Wang
The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28325302/aptamer-drug-conjugates-of-active-metabolites-of-nucleoside-analogs-and-cytotoxic-agents-inhibit-pancreatic-tumor-cell-growth
#3
Sorah Yoon, Kai-Wen Huang, Vikash Reebye, Duncan Spalding, Teresa M Przytycka, Yijie Wang, Piotr Swiderski, Lin Li, Brian Armstrong, Isabella Reccia, Dimitris Zacharoulis, Konstantinos Dimas, Tomokazu Kusano, John Shively, Nagy Habib, John J Rossi
Aptamer-drug conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells while sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer previously described by our group, the pancreatic cancer RNA aptamer P19. To this end, P19 was incorporated with gemcitabine and 5-fluorouracil (5-FU), or conjugated to monomethyl auristatin E (MMAE) and derivative of maytansine 1 (DM1)...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28322785/puromycin-resistant-lentiviral-control-shrna-vector-plko-1-induces-unexpected-cellular-differentiation-of-p19-embryonic-stem-cells
#4
Jyotshna Kanungo
RNA silencing is used as a common method for investigating loss-of-function effects of genes of interest. In mammalian cells, RNA interference (RNAi) or RNA silencing can be achieved by transient siRNA (small or short interfering RNA) transfection or by stable shRNA (short hairpin RNA) systems. Various vectors are used for efficient delivery of shRNA. Lentiviral vectors offer an efficient delivery system for stable and long-term expression of the shRNA in mammalian cells. The widely used lentiviral pLKO.1 plasmid vector is very popular in RNAi studies...
March 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28303954/suppression-of-sin3a-activity-promotes-differentiation-of-pluripotent-cells-into-functional-neurons
#5
Debasish Halder, Chang-Hee Lee, Ji Young Hyun, Gyeong-Eon Chang, Eunji Cheong, Injae Shin
Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299779/the-related-neuronal-endosomal-proteins-neep21-nsg1-and-p19-nsg2-have-divergent-expression-profiles-in-vivo
#6
Kelly Barford, Chan Choo Yap, Noelle D Dwyer, Bettina Winckler
Endosomal maturation and transport constitutes a complex trafficking system present in all cell types. Neurons have adapted their endosomal system to meet their unique and complex needs. These adaptations include repurposing existing proteins to diversify endocytosis and trafficking, as well as preferential expression of certain regulators more highly in neurons than other cell types. These neuronal regulators include the family of Neuron-Specific Gene family members (Nsg), NEEP21 (Nsg1), and P19 (Nsg2). NEEP21/Nsg1 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and β-APP...
March 15, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28284714/strain-specificities-in-cellular-and-molecular-immunopathogenic-mechanisms-underlying-development-of-experimental-autoimmune-encephalomyelitis-in-aged-rats
#7
Mirjana Nacka-Aleksić, Zorica Stojić-Vukanić, Ivan Pilipović, Ivana Vujnović, Biljana Bufan, Mirjana Dimitrijević, Gordana Leposavić
To understand strain-specificities of immune system in aged rats and their immunopathological implications, CD4+ T lymphocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis (EAE) was studied in two strains. Upon immunization for EAE, 22-24-month-old Albino Oxford (AO) rats developed milder neurological deficit of prolonged duration compared with their Dark Agouti (DA) counterparts. Consistently, they exhibited: (i) diminished neuroantigen-specific CD4+ T lymphocyte generation in draining lymph nodes (reflecting lower density of high-affinity IL-2 receptor complex on their surface and higher CD4+FoxP3+CD25+ regulatory cell frequency); (ii) less favorable spinal cord expression of CXCL12 and CCL2, and consequently diminished infiltration of neuroantigen-specific CD4+ T lymphocytes, including highly pathogenic IL-17+IFN-γ+ ones, and inflammatory monocytes into the spinal cord and (iii) subsequently impaired CD4+ T lymphocyte reactivation/survival and differentiation into highly pathogenic IL-17+ cells (reflecting downregulated expression of IL-1β, IL-6 and IL-23/p19)...
March 8, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28271735/tildrakizumab-for-treating-psoriasis
#8
Marco Galluzzo, S D'Adamio, L Bianchi, M Talamonti
Agents that block inflammatory pathways other than tumor necrosis factor (TNF) have represented new options for treating psoriasis in recent years. IL-23 is involved in regulating Th17 cells and is a potent activator of keratinocyte proliferation. Targeting IL-23p19 alone may be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis, with a downregulation of Th17 and Th22 cell responses, while IL-12 blockade is not required to achieve efficacy in these patients. Areas covered: The authors review and provide an update on tildrakizumab, a humanized IgG1 monoclonal antibody that blocks the p19 subunit of IL-23...
March 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28260051/microrna-1-upregulation-promotes-myocardiocyte-proliferation-and-suppresses-apoptosis-during-heart-development
#9
Liping Liu, Yonghua Yuan, Xuehua He, Xiaohui Xia, Xiaoyang Mo
Previous studies have investigated the role of microRNAs (miRs) in heart development to reveal the miRNA mechanism of action in congenital heart disease (CHD) in children. The present study aimed to investigate the role of miR‑1 in heart development in P19 cells. The mRNA level for miR‑1 in P19 cells was detected before or after cardiomyocyte differentiation, using reverse transcription‑quantitative polymerase chain reaction analysis. Expression of cardiomyocyte differentiation markers was also analyzed...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28257975/rapid-and-sensitive-detection-of-microrna-via-the-capture-of-fluorescent-dyes-loaded-albumin-nanoparticles-around-functionalized-magnetic-beads
#10
Tianxiang Wei, Dan Du, Zhaoyin Wang, Weiwei Zhang, Yuehe Lin, Zhihui Dai
MicroRNAs (miRNAs) play important roles in gene regulation and cancer development. Nowadays, it is still a challenge to detect low-abundance miRNAs. Here, we present a magnetic fluorescent miRNA sensing system for the rapid and sensitive detection of miRNAs from cell lysates and serum samples. In this system, albumin nanoparticles (Alb NPs) were prepared from inherent biocompatible bovine serum albumin (BSA). A large number of fluorescent dyes were loaded into Alb NPs to make Alb NPs serve as signal molecular nanocarriers for signal amplification...
February 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28228163/cell-cycle-independent-roles-of-p19-ink4d-in-human-terminal-erythropoiesis
#11
Xu Han, Jing Liu
No abstract text is available yet for this article.
February 23, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28211871/expression-level-is-a-key-determinant-of-e2f1-mediated-cell-fate
#12
Igor Shats, Michael Deng, Adam Davidovich, Carolyn Zhang, Jungeun S Kwon, Dinesh Manandhar, Raluca Gordân, Guang Yao, Lingchong You
The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both. Paradoxically, the downstream target of this network, E2F1, is rarely strongly overexpressed in cancer. E2F1 can induce both proliferation and apoptosis but the factors governing these critical cell fate decisions remain unclear. Previous studies have focused on qualitative mechanisms such as differential cofactors, posttranslational modification or state of other signaling pathways as modifiers of the cell fate decisions downstream of E2F1 activation...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28207964/impaired-nephrogenesis-in-neonatal-rats-with-oxygen-induced-retinopathy
#13
Mayu Nakagawa, Naoto Nishizaki, Amane Endo, Tomonosuke Someya, Yuta Saito, Akira Mizutani, Taichi Hara, Yayoi Murano, Koji Sakuraya, Satoshi Hara, Daisuke Umino, Daishi Hirano, Shuichiro Fujinaga, Yoshiyuki Ohtomo, Toshiaki Shimizu
OBJECTIVES: Preterm neonates are born while nephrogenesis is ongoing and are commonly exposed to factors in a hyperoxic environment that can impair renal development. Oxidative stress has also been implicated in the development of retinopathy of prematurity (ROP). The rat model of oxygen-induced retinopathy (OIR) is the most clinically relevant model of ROP because its biologic features closely resemble those of ROP in preterm infants. We investigated impaired renal development in a rat model of OIR...
February 16, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28193005/mapping-the-energetic-epitope-of-an-antibody-interleukin-23-interaction-with-hydrogen-deuterium-exchange-fast-photochemical-oxidation-of-proteins-mass-spectrometry-and-alanine-shave-mutagenesis
#14
Jing Li, Hui Wei, Stanley R Krystek, Derek Bond, Ty M Brender, Daniel Cohen, Jena Feiner, Nels Hamacher, Johanna Harshman, Richard Y-C Huang, Susan H Julien, Zheng Lin, Kristina Moore, Luciano Mueller, Claire Noriega, Preeti Sejwal, Paul Sheppard, Brenda Stevens, Guodong Chen, Adrienne A Tymiak, Michael L Gross, Lumelle A Schneeweis
Epitope mapping the specific residues of an antibody/antigen interaction can be used to support mechanistic interpretation, antibody optimization, and epitope novelty assessment. Thus, there is a strong need for mapping methods, particularly integrative ones. Here, we report the identification of an energetic epitope by determining the interfacial hot-spot that dominates the binding affinity for an anti-interleukin-23 (anti-IL-23) antibody by using the complementary approaches of hydrogen/deuterium exchange mass spectrometry (HDX-MS), fast photochemical oxidation of proteins (FPOP), alanine shave mutagenesis, and binding analytics...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28179426/extracellular-signal-regulated-kinases-erks-phosphorylate-lin28a-protein-to-modulate-p19-cell-proliferation-and-differentiation
#15
Xiangyuan Liu, Min Chen, Long Li, Liyan Gong, Hu Zhou, Daming Gao
Lin28a, originally discovered in the nematode Caenorhabditis elegans and highly conserved across species, is a well characterized regulator of let-7 microRNA (miRNA) and is implicated in cell proliferation and pluripotency control. However, little is known about how Lin28a function is modulated at the post-translational level and thereby responds to major signaling pathways. Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. By editing lin28a gene with the CRISPR/Cas9-based method, we generated P19 mouse embryonic carcinoma stem cells expressing Lin28a-S200A (phospho-deficient) and Lin28a-S200D (phospho-mimetic) mutants, respectively, to study the functional impact of Ser-200 phosphorylation...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28165883/the-role-of-il-23-in-the-treatment-of-psoriasis
#16
Lluís Puig
The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade...
February 6, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28164768/protective-effect-of-aspirin-against-oligomeric-a%C3%AE-42-induced-mitochondrial-alterations-and-neurotoxicity-in-differentiated-ec-p19-neuronal-cells
#17
Hamendra Singh Parmar, Zbynek Houdek, Martin Pesta, Vaclava Cerna, Pavel Dvorak, Jiri Hatina
Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major causes of neuronal toxicity in Alzheimer's disease. Many recent reports suggest involvement of mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations include increased reactive oxygen species (ROS), mt-DNA depletion, decreased oxidative phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc. These all defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28157724/orchestration-of-late-events-in-erythropoiesis-by-klf1-eklf
#18
Merlin Nithya Gnanapragasam, James J Bieker
PURPOSE OF REVIEW: Transcriptional regulators provide the molecular and biochemical basis for the cell specific properties and characteristics that follow from their central role in establishing tissue-restricted expression. Precise and sequential control of terminal cell divisions, nuclear condensation, and enucleation are defining characteristics within erythropoietic differentiation. This review is focused on KLF1, a central global regulator of this process. RECENT FINDINGS: Studies in the past year have brought a number of proteins that are targets of KLF1 regulation into focus with respect to their roles in terminal erythroid differentiation...
February 2, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28153853/epigenetic-activation-of-mu-opioid-receptor-mor-gene-via-increased-expression-and-function-of-mitogen-and-stress-activated-protein-kinase-1-msk1
#19
Yadav Wagley, Ping-Yee Law, Li-Na Wei, Horace H Loh
Since the discovery of mu opioid receptor (MOR) gene two decades ago, various regulatory factors have been shown to interact with the MOR promoter and modulate transcript levels. However, the majority of early transcriptional studies on MOR gene have not addressed how intracellular signaling pathways mediate extracellular modulators. In this study, we demonstrate that MOR epigenetic regulation requires multiple co-ordinated signals converged at the MOR promoter, involving mitogen-activated protein kinase (MAPK) activation and mitogen-and stress-activated protein kinase (MSK1) - similar ranges of intracellular signaling pathways that are activated by opioid agonists...
February 2, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28152559/t-cell-responses-to-peptides-of-goodpasture-autoantigen-in-patients-with-anti-glomerular-basement-membrane-disease
#20
Shui-Yi Hu, Xiao-Yu Jia, Qiu-Hua Gu, Chong-Yan Yu, Xu-Yang Cheng, Qi-Zhuang Jin, Fu-de Zhou, Zhao Cui, Ming-Hui Zhao
AIM: Cell-mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti-glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti-GBM patients, aiming to identify the epitopes and their clinical significance. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti-GBM disease. Twenty-four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1...
February 2, 2017: Nephrology
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