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https://www.readbyqxmd.com/read/28723387/sigma-1-receptor-activation-modifies-intracellular-calcium-exchange-in-the-g93a-hsod1-als-model
#1
Vedrana Tadić, Ayse Malci, Nadine Goldhammer, Beatrice Stubendorff, Saikata Sengupta, Tino Prell, Silke Keiner, Jingyu Liu, Madlen Guenther, Christiane Frahm, Otto W Witte, Julian Grosskreutz
Aberrations in intracellular calcium (Ca(2+)) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca(2+) concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca(2+) cycle (ERMCC). The ER supplies Ca(2+) to the mitochondria at close contacts between the two organelles, i.e. the mitochondria-associated ER membranes (MAMs). The Sigma 1 receptor (Sig1R) is enriched at MAMs, where it acts as an inter-organelle signalling modulator...
July 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28721035/intracellular-interactions-of-umeclidinium-and-vilanterol-in-human-airway-smooth-muscle
#2
Nooreen Shaikh, Malcolm Johnson, David A Hall, Kian Fan Chung, John H Riley, Sally Worsley, Pankaj K Bhavsar
BACKGROUND: Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β2-adrenoceptor (β2R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs). MATERIALS AND METHODS: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh])...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28719356/co-incubation-of-pmn-and-caco-2-cells-modulates-inflammatory-potential
#3
M B Schaefer, C A Schaefer, M Hecker, R E Morty, M Witzenrath, W Seeger, K Mayer
Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28719042/serotonergic-paraneurons-in-the-female-mouse-urethral-epithelium-and-their-potential-role-in-peripheral-sensory-information-processing
#4
F Aura Kullmann, Huiyi H Chang, Christian Gauthier, Bronagh M McDonnell, Jih-Chao Yeh, Dennis R Clayton, Anthony J Kanai, William C de Groat, Gerard L Apodaca, Lori A Birder
AIM: The mechanisms underlying detection and transmission of sensory signals arising from visceral organs, such as the urethra, are poorly understood. Recently, specialized ACh-expressing cells embedded in the urethral epithelium have been proposed as chemosensory sentinels for detection of bacterial infection. Here we examined the morphology and potential role in sensory signaling of a different class of specialized cells that express serotonin (5-HT), termed paraneurons. METHODS: Urethrae, dorsal root ganglia neurons and spinal cords were isolated from adult female mice and used for immunohistochemistry and calcium imaging...
July 18, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28717974/improvement-of-oral-bioavailability-of-lopinavir-without-co-administration-of-ritonavir-using-microspheres-of-thiolated-xyloglucan
#5
Ashwini R Madgulkar, Mangesh R Bhalekar, Ashwini A Kadam
Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T80, surface morphology, and mucoadhesion employing in vitro wash off test...
July 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28717204/a-drug-carrier-for-sustained-zero-order-release-of-peptide-therapeutics
#6
Ya-Nan Zhao, Xiaoyu Xu, Na Wen, Rui Song, Qingbin Meng, Ying Guan, Siqi Cheng, Danni Cao, Yansheng Dong, Jiankun Qie, Keliang Liu, Yongjun Zhang
Peptides have great potential as therapeutic agents, however, their clinic applications are severely hampered by their instability and short circulation half-life. Zero-order release carriers could not only extend the circulation lifetime of peptides, but also maintain the plasma drug level constant, and thus maximize their therapeutic efficacy and minimize their toxic effect. Here using PEGylated salmon calcitonin (PEG-sCT)/tannic acid (TA) film as an example, we demonstrated that hydrogen-bonded layer-by-layer films of a PEGylated peptide and a polyphenol could be a platform for zero-order peptide release...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#7
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#8
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28715390/mammalian-cell-encapsulation-in-alginate-beads-using-a-simple-stirred-vessel
#9
Corinne A Hoesli, Roger L J Kiang, Kamini Raghuram, René G Pedroza, Karen E Markwick, Antonio M R Colantuoni, James M Piret
Cell encapsulation in alginate beads has been used for immobilized cell culture in vitro as well as for immunoisolation in vivo. Pancreatic islet encapsulation has been studied extensively as a means to increase islet survival in allogeneic or xenogeneic transplants. Alginate encapsulation is commonly achieved by nozzle extrusion and external gelation. Using this method, cell-containing alginate droplets formed at the tip of nozzles fall into a solution containing divalent cations that cause ionotropic alginate gelation as they diffuse into the droplets...
June 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28714662/enhancing-the-osteogenic-capability-of-core-shell-bilayered-bioceramic-microspheres-with-adjustable-biodegradation
#10
Xiurong Ke, Chen Zhuang, Xianyan Yang, Jia Fu, Sanzhong Xu, Lijun Xie, Zhongru Gou, Juncheng Wang, Lei Zhang, Guojing Yang
This study describes the fabrication and biological evaluation of core-shell bilayered bioceramic microspheres with adjustable compositional distribution via a coaxial bilayer capillary system. Beyond the homogeneous hybrid composites, varying the diameter of capillary nozzles and the composition of the bioceramic slurries makes it easy to create bilayered β-tricalcium phosphate (CaP)/β-calcium silicate (CaSi) microspheres with controllable compositional distribution in the core or shell layer. Primary investigations in vitro revealed that biodegradation could be adjusted by compositional distribution or shell thickness and that poorly soluble CaP located on the shell layer of CaP or CaSi@CaP microspheres was particularly beneficial for mesenchymal stem cell adhesion and growth in the early stage, but the ion release from the CaP@CaSi exhibited a potent stimulating effect on alkaline phosphatase expression of the cells at longer times...
July 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28713282/the-n-terminal-region-of-the-ryanodine-receptor-affects-channel-activation
#11
Andrea Faltinova, Nataša Tomaskova, Marián Antalik, Jozef Sevcik, Alexandra Zahradnikova
Mutations in the cardiac ryanodine receptor (RyR2), the ion channel responsible for release of calcium ions from intracellular stores into cytoplasm, are the cause of several inherited cardiac arrhythmias. At the molecular level, disease symptoms can be mimicked by domain peptides from mutation-prone regions of RyR2 that bind to RyR2 and activate it. Here we show that the domain peptide DPcpvtN2, corresponding to the central helix of the N-terminal region of RyR2, activates the RyR2 channel. Structural modeling of interaction between DPcpvtN2 and the N-terminal region of RyR2 in the closed and open conformation provided three plausible structures of the complex...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713009/aeromonas-hydrophila-induced-alterations-in-cytosolic-calcium-activate-pro-apoptotic-cpkc-mek1-2-tnf%C3%AE-axis-in-infected-headkidney-macrophages-of-clarias-gariepinus
#12
Asha Shelly, Chaitali Banerjee, Gunjan Kumar Saurav, Atish Ray, Vipin Singh Rana, Rajagopal Raman, Shibnath Mazumder
Alterations in intracellular-calcium (Ca(2+))i homeostasis is critical to Aeromonas hydrophila-induced headkidney macrophages (HKM) apoptosis of Clarias gariepinus, though the implications are poorly understood. Here, we describe the role of intermediate molecules of Ca(2+-)signaling pathway that are involved in HKM apoptosis. We observed phosphoinositide-3-kinase/phospholipase C is critical for (Ca(2+))i release in infected HKM. Heightened protein kinase-C (PKC) activity and phosphorylation of MEK1/2-ERK1/2 was noted which declined in presence of 2-APB, Go6976 and PD98059, inhibitors to IP3-receptor, conventional PKC isoforms (cPKC) and MEK1/2 respectively implicating Ca(2+)/cPKC/MEK-ERK1/2 axis imperative in A...
July 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28711494/development-of-membrane-ion-channels-during-neural-differentiation-from-human-embryonic-stem-cells
#13
Sara Mirsadeghi, Ebrahim Shahbazi, Katayoun Hemmesi, Shiva Nemati, Hossein Baharvand, Javad Mirnajafi-Zadeh, Sahar Kiani
OBJECTIVE: For human embryonic stem cells (hESCs) to differentiate into neurons, enormous changes has to occur leading to trigger action potential and neurotransmitter release. We attempt to determine the changes in expression of voltage gated channels (VGCs) and their electrophysiological properties during neural differentiation. MATERIALS AND METHODS: The relative expressions of α-subunit of voltage gated potassium, sodium and calcium channels were characterized by qRT-PCR technique...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710476/inflammatory-pain-control-by-blocking-oxidized-phospholipid-mediated-trp-channel-activation
#14
Beatrice Oehler, Katrin Kistner, Corinna Martin, Jürgen Schiller, Rafaela Mayer, Milad Mohammadi, Reine-Solange Sauer, Milos R Filipovic, Francisco R Nieto, Jan Kloka, Diana Pflücke, Kerstin Hill, Michael Schaefer, Marzia Malcangio, Peter W Reeh, Alexander Brack, Robert Blum, Heike L Rittner
Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710422/enmd-1068-inhibits-liver-fibrosis-through-attenuation-of-tgf-%C3%AE-1-smad2-3-signaling-in-mice
#15
Quan Sun, Yan Wang, Jie Zhang, Jing Lu
Protease-activated receptor 2 (PAR-2) plays an important role in the pathogenesis of liver fibrosis. We studied the effect of N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (ENMD-1068), a PAR-2 antagonist, on the development of CCl4-induced liver fibrosis in mice and activation of hepatic stellate cells (HSCs) isolated from the mice. Before CCl4 injection, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control twice per week for 4 weeks...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710416/calquo-2-automated-fourier-space-population-level-quantification-of-global-intracellular-calcium-responses
#16
Angela M Lee, Huw Colin-York, Marco Fritzsche
Intracellular calcium acts as a secondary messenger in a wide variety of crucial biological signaling processes. Advances in fluorescence microscopy and calcium sensitive dyes has led to the routine quantification of calcium responses in non-excitable cells. However, the automatization of global intracellular calcium analysis at the single-cell level within a large population simultaneously remains challenging. One software, CalQuo (Calcium Quantification), offers some automatic features in calcium analysis...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709993/intracellular-calcium-release-through-ip3r-or-ryr-contributes-to-secondary-axonal-degeneration
#17
Ben C Orem, Nicolas Pelisch, Joshua Williams, Jacqueline M Nally, David P Stirling
Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca(2+) store mediated intra-axonal Ca(2+) release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model...
July 11, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28708434/epithelial-cells-induce-a-cyclooxygenase-1-dependent-endogenous-reduction-in-airway-smooth-muscle-contractile-phenotype
#18
Michael J O'Sullivan, Elizabeth Gabriel, Alice Panariti, Chan Y Park, Gijs Ijpma, Jeffrey J Fredberg, Anne-Marie Lauzon, James G Martin
Airway smooth muscle (ASM) cells are phenotypically regulated to exist in either a proliferative or a contractile state. However the influence of other airway structural cell types on ASM cell phenotype is largely unknown. Although epithelial cells are known to drive ASM proliferation, their effects on the contractile phenotype are uncertain. In the current study we tested the hypothesis that epithelial cells reduce the contractile phenotype of ASM cells. To do so, we measured force production by traction microscopy, gene and protein expression as well as calcium release by Fura-2 ratiometric imaging...
July 14, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28708217/evaluation-of-calcium-ca2-and-hydroxide-oh-ion-diffusion-rates-of-indirect-pulp-capping-materials
#19
Merve Kurun Aksoy, Firdevs Tulga Oz, Kaan Orhan
INTRODUCTION: The aim of this study was to evaluate and compare the calcium (Ca2+) and hydroxide (OH-) ion release of 4 artificially produced pulp capping materials (MTA, Biodentin, TheraCal LC, Calsimol) used for indirect pulp capping treatment. METHODS: In total, 70 freshly extracted human third molar teeth were used for the study. Cavities of extracted teeth were prepared by round burs. The remaining dentin thickness (1 ± 0.3 mm) tissue was measured by a micrometer and cone beam computerized tomography...
July 8, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28707481/protective-effects-of-melatonin-and-memantine-in-human-retinal-pigment-epithelium-arpe-19-cells-against-2-ethylpyridine-induced-oxidative-stress-implications-for-age-related-macular-degeneration
#20
Handan Bardak, Abdülhadi Cihangir Uğuz, Yavuz Bardak
PURPOSE: To investigate the possible protective effects of melatonin and memantine (MMT) against 2-ethylpyridine (2-EP)-induced oxidative stress and mitochondrial dysfunction in human RPE (ARPE-19) cells in vitro. MATERIALS AND METHODS: The ARPE-19 cells were divided into seven groups. Oxidative stress was triggered by incubating the ARPE-19 cells with 30 µM of 2-EP for 24 hours. Then, 200 µM of melatonin was administered over three days and 20 µM of MMT over six hours prior to the experiment...
July 14, 2017: Cutaneous and Ocular Toxicology
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