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https://www.readbyqxmd.com/read/28532017/effects-of-pore-orientation-on-in-vitro-properties-of-retinoic-acid-loaded-plga-gelatin-scaffolds-for-artificial-peripheral-nerve-application
#1
Farnaz Ghorbani, Ali Zamanian, Hanieh Nojehdehian
Different manufacturing processes of scaffolds affect their main properties by altering the microstructure of pores. In this study, poly (lactic-co-glycolic acid) (PLGA) scaffolds were synthesized by both freeze casting and freeze drying methods. Scanning electron microscopy (SEM) micrographs demonstrated a unidirectional microstructure in the freeze-cast and a number of random pores in the freeze-dried scaffolds. According to the results, the formation of a lamellar microstructure increased the mechanical strength, swelling ratio, biodegradation behavior and drug release level...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28527889/enhanced-cardiomyogenic-induction-of-mouse-pluripotent-cells-by-cyclic-mechanical-stretch
#2
Akankshya Shradhanjali, Brandon D Riehl, Jeong Soon Lee, Ligyeom Ha, Jung Yul Lim
The cardiac milieu is mechanically active with spontaneous contraction beginning from early development and persistent through maturation and homeostasis, suggesting that mechanical loading may provide biomimetic myocardial developmental signal. In this study, we tested the role of cyclic mechanical stretch loading in the cardiomyogenesis of pluripotent murine embryonic (P19) stem cells. A Flexcell tension system was utilized to apply equiaxial stretch (12% strain, 1.25 Hz frequency) to P19 cell-derived embryoid bodies (EBs)...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28512399/protein-s-negatively-regulates-neural-stem-cell-self-renewal-through-bmi-1-signaling
#3
Katya Zelentsova-Levytskyi, Ziv Talmi, Ghada Abboud-Jarrous, Tal Capucha, Tamar Sapir, Tal Burstyn-Cohen
Revealing the molecular mechanisms underlying neural stem cell self-renewal is a major goal toward understanding adult brain homeostasis. The self-renewing potential of neural stem and progenitor cells (NSPCs) must be tightly regulated to maintain brain homeostasis. We recently reported the expression of Protein S (PROS1) in adult hippocampal NSPCs, and revealed its role in regulation of NSPC quiescence and neuronal differentiation. Here, we investigate the effect of PROS1 on NSPC self-renewal and show that genetic ablation of Pros1 in neural progenitors increased NSPC self-renewal by 50%...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28504123/erythropoietin-and-small-molecule-agonists-of-the-tissue-protective-erythropoietin-receptor-increase-fxn-expression-in-neuronal-cells-in-vitro-and-in-fxn-deficient-kiko-mice-in-vivo
#4
James L Miller, Myriam Rai, Normand L Frigon, Massimo Pandolfo, Juha Punnonen, Jeffrey R Spencer
Friedreich's ataxia (FRDA) is a progressive neurodegenerative disease caused by reduced levels of the mitochondrial protein frataxin (FXN). Recombinant human erythropoietin (rhEPO) increased FXN protein in vitro and in early clinical studies, while no published reports evaluate rhEPO in animal models of FRDA. STS-E412 and STS-E424 are novel small molecule agonists of the tissue-protective, but not the erythropoietic EPO receptor. We find that rhEPO, STS-E412 and STS-E424 increase FXN expression in vitro and in vivo...
May 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28500669/anti-m%C3%A3-llerian-hormone-signalling-is-influenced-by-follistatin-288-but-not-fourteen-other-transforming-growth-factor-beta-superfamily-regulators
#5
Yui Kawagishi, Michael W Pankhurst, Yoshio Nakatani, Ian S McLennan
The hypothesis that, in contrast to other transforming growth factor-beta (TGFβ) superfamily ligands, the dose-response curve of Anti-Müllerian hormone (AMH) is unmodulated was tested by examining whether known TGFB superfamily modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMHC and AMHN,C activated the reporter with an EC50 of approximately 0.5 nM. Follistatins (FS) produced concentration-dependent increases in AMHC - and AMHN,C -initiated reporter activity, with FS288 being more potent than FS315; however, the maximum bioactivity of AMH was not altered by either follistatin...
May 13, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28491095/angelica-sinensis-polysaccharide-prevents-hematopoietic-stem-cells-senescence-in-d-galactose-induced-aging-mouse-model
#6
Xinyi Mu, Yanyan Zhang, Jing Li, Jieyu Xia, Xiongbin Chen, Pengwei Jing, Xiaoying Song, Lu Wang, Yaping Wang
Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1(+) HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28423301/risankizumab-versus-ustekinumab-for-moderate-to-severe-plaque-psoriasis
#7
RANDOMIZED CONTROLLED TRIAL
Kim A Papp, Andrew Blauvelt, Michael Bukhalo, Melinda Gooderham, James G Krueger, Jean-Philippe Lacour, Alan Menter, Sandra Philipp, Howard Sofen, Stephen Tyring, Beate R Berner, Sudha Visvanathan, Chandrasena Pamulapati, Nathan Bennett, Mary Flack, Paul Scholl, Steven J Padula
BACKGROUND: Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16)...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28411872/induction-therapy-with-the-selective-interleukin-23-inhibitor-risankizumab-in-patients-with-moderate-to-severe-crohn-s-disease-a-randomised-double-blind-placebo-controlled-phase-2-study
#8
Brian G Feagan, William J Sandborn, Geert D'Haens, Julián Panés, Arthur Kaser, Marc Ferrante, Edouard Louis, Denis Franchimont, Olivier Dewit, Ursula Seidler, Kyung-Jo Kim, Markus F Neurath, Stefan Schreiber, Paul Scholl, Chandrasena Pamulapati, Bojan Lalovic, Sudha Visvanathan, Steven J Padula, Ivona Herichova, Adina Soaita, David B Hall, Wulf O Böcher
BACKGROUND: The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in patients with moderately-to-severely active Crohn's disease. METHODS: In this randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients at 36 referral sites in North America, Europe, and southeast Asia...
April 29, 2017: Lancet
https://www.readbyqxmd.com/read/28388677/the-barley-stripe-mosaic-virus-%C3%AE-b-protein-promotes-chloroplast-targeted-replication-by-enhancing-unwinding-of-rna-duplexes
#9
Kun Zhang, Yongliang Zhang, Meng Yang, Songyu Liu, Zhenggang Li, Xianbing Wang, Chenggui Han, Jialin Yu, Dawei Li
RNA viruses encode various RNA binding proteins that function in many steps of viral infection cycles. These proteins function as RNA helicases, methyltransferases, RNA-dependent RNA polymerases, RNA silencing suppressors, RNA chaperones, movement proteins, and so on. Although many of the proteins bind the viral RNA genome during different stages of infection, our knowledge about the coordination of their functions is limited. In this study, we describe a novel role for the Barley stripe mosaic virus (BSMV) γb as an enhancer of αa RNA helicase activity, and we show that the γb protein is recruited by the αa viral replication protein to chloroplast membrane sites of BSMV replication...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28374796/identification-of-novel-mage-g1-interacting-partners-in-retinoic-acid-induced-p19-neuronal-differentiation-using-silac-based-proteomics
#10
Yong Liu, Yujian Chen, Shide Lin, Shuguang Yang, Shaojun Liu
MAGE-G1 is a protein plays role in the early process of neurogenesis. However, the fundamental roles MAGE-G1 played in neurogenesis have not yet been completely understood. Finding the partners MAGE-G1 interacting with will surely contribute to the function study of MAGE-G1. In this study, using Stable Isotope Labeling by Amino acids in Cell culture-immunoprecipitation quantitative proteomics, we screened the interacting proteins of MAGE-G1 during retinoic acid -induced neuronal differentiation of P19 cells and firstly found that FSCN1 and VIME were potential novel MAGE-G1-interacting proteins...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373885/mechanisms-regulating-stemness-and-differentiation-in-embryonal-carcinoma-cells
#11
REVIEW
Gregory M Kelly, Mohamed I Gatie
Just over ten years have passed since the seminal Takahashi-Yamanaka paper, and while most attention nowadays is on induced, embryonic, and cancer stem cells, much of the pioneering work arose from studies with embryonal carcinoma cells (ECCs) derived from teratocarcinomas. This original work was broad in scope, but eventually led the way for us to focus on the components involved in the gene regulation of stemness and differentiation. As the name implies, ECCs are malignant in nature, yet maintain the ability to differentiate into the 3 germ layers and extraembryonic tissues, as well as behave normally when reintroduced into a healthy blastocyst...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28351885/loss-of-the-rna-helicase-skiv2l2-impairs-mitotic-progression-and-replication-dependent-histone-mrna-turnover-in-murine-cell-lines
#12
Alexis M Onderak, James T Anderson
RNA surveillance via the nuclear exosome requires cofactors such as the helicase SKIV2L2 to process and degrade certain noncoding RNAs. This research aimed to characterize the phenotype associated with RNAi knockdown of Skiv2l2 in two murine cancer cell lines: Neuro2A and P19. SKIV2L2 depletion in Neuro2A and P19 cells induced changes in gene expression indicative of cell differentiation and reduced cellular proliferation by thirty percent. Propidium iodide-based cell cycle analysis of Skiv2l2 knockdown cells revealed defective progression through G2/M phase and an accumulation of mitotic cells, suggesting SKIV2L2 contributes to mitotic progression...
March 28, 2017: RNA
https://www.readbyqxmd.com/read/28337019/apigenin-induced-lysosomal-degradation-of-%C3%AE-catenin-in-wnt-%C3%AE-catenin-signaling
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
June 1, 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
#19
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
#20
Marco Galluzzo, Simone D'adamio, Luca Bianchi, Marina 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 17, 2017: Expert Opinion on Biological Therapy
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