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https://www.readbyqxmd.com/read/28806855/functional-stem-cell-integration-into-neural-networks-assessed-by-organotypic-slice-cultures
#1
David Forsberg, Charoensri Thonabulsombat, Johan Jäderstad, Linda Maria Jäderstad, Petri Olivius, Eric Herlenius
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host...
August 14, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28806787/antagonism-of-proteasome-inhibitor-induced-heme-oxygenase-1-expression-by-pink1-mutation
#2
Xiang-Jun Sheng, Hunag-Ju Tu, Wei-Lin Chien, Kai-Hsiang Kang, Dai-Hua Lu, Horng-Huei Liou, Ming-Jen Lee, Wen-Mei Fu
PTEN-induced putative kinase 1 (PINK1) is an integral protein in the mitochondrial membrane and maintains mitochondrial fidelity. Pathogenic mutations in PINK1 have been identified as a cause of early-onset autosomal recessive familial Parkinson's disease (PD). The ubiquitin proteasome pathway is associated with neurodegenerative diseases. In this study, we investigated whether mutations of PINK1 affects the cellular stress response following proteasome inhibition. Administration of MG132, a peptide aldehyde proteasome inhibitor, significantly increased the expression of heme oxygenase-1 (HO-1) in rat dopaminergic neurons in the substantia nigra and in the SH-SY5Y neuronal cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28806770/increasing-creatine-kinase-activity-protects-against-hypoxia-reoxygenation-injury-but-not-against-anthracycline-toxicity-in-vitro
#3
Sevasti Zervou, Hannah J Whittington, Philip J Ostrowski, Fang Cao, Jack Tyler, Hannah A Lake, Stefan Neubauer, Craig A Lygate
The creatine kinase (CK) phosphagen system is fundamental to cellular energy homeostasis. Cardiomyocytes express three CK isoforms, namely the mitochondrial sarcomeric CKMT2 and the cytoplasmic CKM and CKB. We hypothesized that augmenting CK in vitro would preserve cell viability and function and sought to determine efficacy of the various isoforms. The open reading frame of each isoform was cloned into pcDNA3.1, followed by transfection and stable selection in human embryonic kidney cells (HEK293). CKMT2- CKM- and CKB-HEK293 cells had increased protein and total CK activity compared to non-transfected cells...
2017: PloS One
https://www.readbyqxmd.com/read/28806746/selective-small-chemical-inhibitors-of-protein-arginine-methyltransferase-5-with-anti-lung-cancer-activity
#4
Gui-Mei Kong, Min Yu, Zhongping Gu, Zhi Chen, Rui-Ming Xu, Deon O'Bryant, Zhengxin Wang
Protein arginine methyltransferase 5 (PRMT5) plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#5
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28806688/concentration-dependent-transcriptome-responses-of-zebrafish-embryos-after-exposure-to-cadmium-cobalt-and-copper
#6
Laura Sonnack, Thorsten Klawonn, Ralf Kriehuber, Henner Hollert, Christoph Schäfers, Martina Fenske
Environmental metals are known to cause harmful effects to fish of which many molecular mechanisms still require elucidation. Particularly concentration dependence of gene expression effects is unclear. Focusing on this matter, zebrafish embryo toxicity tests were used in combination with transcriptomics. Embryos were exposed to three concentrations of copper (CuSO4), cadmium (CdCl2) and cobalt (CoSO4) from just after fertilization until the end of the 48hpf pre- and 96hpf post-hatch stage. The RNA was then analyzed on Agilent's Zebrafish (V3, 4×44K) arrays...
August 2, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28806519/pluronic-p85-f68-micelles-of-baicalein-could-interfere-with-mitochondria-to-overcome-mrp2-mediated-efflux-and-offer-improved-anti-parkinsonian-activity
#7
Tongkai Chen, Ye Li, Chuwen Li, Xiang Yi, Ruibing Wang, Simon Ming Yuen Lee, Ying Zheng
Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40...
August 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28806446/sema3a-reduces-sprouting-of-adult-rod-photoreceptors-in-vitro
#8
Frank Kung, Weiwei Wang, Tracy S Tran, Ellen Townes-Anderson
Purpose: Rod photoreceptor terminals respond to retinal injury with retraction and sprouting. Since the guidance cue Semaphorin3A (Sema3A) is observed in the retina after injury, we asked whether Sema3A contributes to structural plasticity in rod photoreceptors. Methods: We used Western blots and alkaline phosphatase (AP)-tagged neuropilin-1 (NPN-1) to detect the expression of Sema3A in an organotypic model of porcine retinal detachment. We then examined Sema3A binding to cultured salamander rod photoreceptors using AP-tagged Sema3A...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28806396/inhibiting-myc-binding-to-the-e-box-dna-motif-by-me47-decreases-tumour-xenograft-growth
#9
L C Lustig, D Dingar, W B Tu, C Lourenco, M Kalkat, I Inamoto, R Ponzielli, W C W Chan, J A Shin, L Z Penn
Developing therapeutics to effectively inhibit the MYC oncoprotein would mark a key advance towards cancer patient care as MYC is deregulated in over 50% of human cancers. MYC deregulation is correlated with aggressive disease and poor patient outcome. Despite strong evidence in mouse models that inhibiting MYC would significantly impact tumour cell growth and patient survival, traditional approaches have not yet yielded the urgently needed therapeutic agents that directly target MYC. MYC functions through its interaction with MAX to regulate gene transcription by binding to E-box DNA response elements of MYC target genes...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806294/the-tissue-engineered-tendon-bone-interface-in-vitro-and-in-vivo-synergistic-effects-of-adipo-derived-stem-cells-platelet-rich-plasma-and-extracellular-matrix-hydrogel
#10
Rory McGoldrick, Arhana Chattopadhyay, Christopher Crowe, Grace Chiou, Kenneth Hui, Simon Farnebo, Christopher Davis, Anais Le Grand, Molly Jacobs, Hung Pham, James Chang
INTRODUCTION: Suboptimal healing of the tendon bone interface (TBI) remains an unsolved problem. One solution is a biocompatible tissue engineered construct that promotes augmented healing. We hypothesisze that 1.) the presence of Platelet Rich Plasma (PRP) and prolonged in vitro incubation produces tissue engineered tendon bone interface scaffolds with greater reseeding of viable Adipo-derived Stem Cells (ADSC) and 2.) when implanted with extracellular matrix hydrogel, constructs will display superior in vivo strength repair and biocompatibility...
August 3, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28806139/mask-mitigates-mapt-and-fus-induced-degeneration-by-enhancing-autophagy-through-lysosomal-acidification
#11
Mingwei Zhu, Sheng Zhang, Xiaolin Tian, Chunlai Wu
Accumulation of intracellular misfolded or damaged proteins is associated with both normal aging and late-onset degenerative diseases. Two cellular clearance mechanisms, the ubiquitin-proteasome system (UPS) and the macroautophagy/autophagy-lysosomal pathway, work in concert to degrade harmful protein aggregates and maintain protein homeostasis. Here we show that Mask, an Ankyrin-repeat and KH-domain containing protein, plays a key role in promoting autophagy flux and mitigating degeneration caused by protein aggregation or impaired UPS function...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28806138/lipid-droplets-and-lipotoxicity-during-autophagy
#12
Truc B Nguyen, James A Olzmann
Lipid droplets (LDs) are neutral lipid storage organelles that provide a rapidly accessible source of fatty acids (FAs) for energy during periods of nutrient deprivation. Surprisingly, lipids released by the macroautophagic/autophagic breakdown of membranous organelles are packaged and stored in new LDs during periods of prolonged starvation. Why cells would store FAs during an energy crisis was unknown. In our recent study, we demonstrated that FAs released during MTORC1-regulated autophagy are selectively channeled by DGAT1 (diacylglycerol O-acyltransferase 1) into triacylglycerol (TAG)-rich LDs...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28806133/autophagy-dictates-metabolism-and-differentiation-of-inflammatory-immune-cells
#13
Thomas Riffelmacher, Felix Clemens Richter, Anna Katharina Simon
The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. Particularly, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28806072/modeling-of-the-passive-permeation-of-mercury-and-methylmercury-complexes-through-a-bacterial-cytoplasmic-membrane
#14
Jing Zhou, Micholas Dean Smith, Sarah J Cooper, Xiaolin Cheng, Jeremy C Smith, Jerry M Parks
Cellular uptake and export are important steps in the biotransformation of mercury (Hg) by microorganisms. However, the mechanisms of transport across biological membranes remain unclear. Membrane-bound transporters are known to be relevant, but passive permeation may also be involved. Inorganic Hg(II) and methylmercury ([CH3Hg]+) are commonly complexed with thiolate ligands. Here, we have performed extensive molecular dynamics simulations of the passive permeation of Hg(II) and [CH3Hg]+ complexes with thiolate ligands through a model bacterial cytoplasmic membrane...
August 14, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28806059/bis-pyrene-doped-cationic-dipeptide-nanoparticles-for-two-photon-activated-photodynamic-therapy
#15
Bingbing Sun, Lei Wang, Qi Li, Ping-Ping He, Huiling Liu, Hao Wang, Yang Yang, Junbai Li
At present, one of main problems for photodynamic therapy (PDT) is how to improve the treatment depth. Two-photon activated (TPA) developed recently provide a possible solution for it. In this work, we report the energy-transferring assembled cationic dipeptide nanoparticles for two-photon activated photodynamic therapy (TPA-PDT). In the nanoparticles, the co-encapsulated two-photon fluorescent dye bis(pyrene) (BP) is an energy donor and a photosensitizer rose bengal (RB) is an acceptor based on an intraparticle fluorescence resonance energy transfer (FRET) mechanism...
August 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28806058/metalloproteases-of-the-inner-mitochondrial-membrane
#16
Roman Levytskyy, Iryna Bohovych, Oleh Khalimonchuk
The inner mitochondrial membrane (IM) is among most protein-rich cellular compartments. The metastable IM sub-proteome where the concentration of proteins is approaching oversaturation creates a challenging protein folding environment with high probability for protein malfunction or aggregation. Failure to maintain protein homeostasis in such a setting can impair functional integrity of the mitochondria and drive clinical manifestations. The IM is equipped with a series of highly conserved, proteolytic complexes dedicated to the maintenance of normal protein homeostasis within this mitochondrial sub-compartment...
August 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28806057/rational-design-and-multi-biological-profiling-of-novel-donepezil-trolox-hybrids-against-alzheimer-s-disease-with-cholinergic-antioxidant-neuroprotective-and-cognition-enhancing-properties
#17
Pei Cai, Si-Qiang Fang, Xue-Lian Yang, Jia-Jia Wu, Qiao-Hong Liu, Hao Hong, Xiao-Bing Wang, Lingyi Kong
A novel series of donepezil-trolox hybrids were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41...
August 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28806053/de-blurring-signal-network-dynamics
#18
Dominic Kamps, Leif Dehmelt
To orchestrate the function and development of multicellular organisms, cells integrate intra- and extracellular information. This information is processed via signal networks in space and time, steering dynamic changes in cellular structure and function. Defects in those signal networks can lead to developmental disorders or cancer. However, experimental analysis of signal networks is challenging as their state changes dynamically and differs between individual cells. Thus, causal relationships between network components are blurred if lysates from large cell populations are analyzed...
August 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28806029/atrial-fibrillation-induced-by-carbon-monoxide-poisoning-and-successful-treatment-with-hyperbaric-oxygen
#19
Maheedhar Gedela, Nathan Y Weltman, Naga Sushma Chavvakula, Paul L Carpenter, Tamera Sturm
Carbon monoxide (CO) intoxication is one of the major public health hazards which may go unnoticed as this is a colorless, odorless and tasteless gas. The manifestations of the CO poisoning are far-reaching. Although CO affects almost every organ in the body, cerebral and myocardial involvement are predominant due to the hypoxia-induced cellular damage. The mainstay treatment is providing high-flow oxygen and in some instances hyperbaric oxygen therapy. In the literature, there have been few cases of CO poisoning-induced atrial fibrillation (AF) reported...
July 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28805991/molecular-recognition-mediated-transformation-of-single-chain-polymer-nanoparticles-into-crosslinked-polymer-films
#20
Clare Sarah Mahon, Christopher J McGurk, Scott M D Watson, Martin A Fascione, Chadamas Sakonsinsiri, William Bruce Turnbull, David Andrew Fulton
We describe single-chain polymer nanoparticles (SCNPs) possessing intramolecular dynamic covalent crosslinks that can transform into polymer films through a molecular recognition-mediated crosslinking process. The SCNPs utilize molecular recognition with surface-immobilized proteins to concentrate themselves upon a substrate, bringing the SCNPs into close spatial proximity with one another and allowing their dynamic covalent crosslinkers to undergo intra-to interpolymer chain crosslinking leading to the formation of polymeric film...
August 14, 2017: Angewandte Chemie
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