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https://www.readbyqxmd.com/read/29458206/mucoadhesive-self-emulsifying-delivery-systems-for-ocular-administration-of-econazole
#1
Ibrahim A Elbahwy, Noemi Lupo, Hany M Ibrahim, Hatem R Ismael, Alaa A Kasem, Cagri Caliskan, Barbara Matuszczak, Andreas Bernkop-Schnürch
AIM: Development of mucoadhesive self-emulsifying drug delivery systems (SEDDS) providing a prolonged ocular residence time for poorly soluble active pharmaceutical ingredient. METHODS: L-Cysteine was covalently linked to 6-mercaptonicotinamide. The obtained ligand, Cysteine-6- mercaptonicotinamide (Cys-6-MNA) was attached to Eudragit® L100-55 via a carbodiimide mediated amide bond formation. The resulting entirely S-protected thiolated Eudragit® L100-55 was characterized regarding the degree of modification as well as stability toward oxidation in the presence of strong oxidizing agent (H2 O2 )...
February 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29458199/alpha-synuclein-oligomers-impair-memory-through-glial-cell-activation-and-via-toll-like-receptor-2
#2
Pietro La Vitola, Claudia Balducci, Milica Cerovic, Giulia Santamaria, Edoardo Brandi, Federica Grandi, Laura Caldinelli, Laura Colombo, Maria Grazia Morgese, Luigia Trabace, Loredano Pollegioni, Diego Albani, Gianluigi Forloni
Alpha-synuclein oligomers (α-synOs) are emerging as crucial factors in the pathogenesis of synucleinopathies. Although the connection between neuroinflammation and α-syn still remains elusive, increasing evidence suggests that extracellular moieties activate glial cells leading to neuronal damage. Using an acute mouse model, we explored whether α-synOs induce memory impairment in association to neuroinflammation, addressing Toll-like receptors 2 and 4 (TLR2 and TLR4) involvement. We found that α-synOs abolished mouse memory establishment in association to hippocampal glial activation...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458195/human-dorsal-root-ganglion-pulsed-radiofrequency-treatment-modulates-cerebrospinal-fluid-lymphocytes-and-neuroinflammatory-markers-in-chronic-radicular-pain
#3
Basabjit Das, Melissa Conroy, David Moore, Joanne Lysaght, Connail McCrory
Radicular pain is a common cause of disability. Traditionally treatment has been either epidural steroid injection providing short-term relief or surgery with associated complications. Pulsed radiofrequency (PRF) applied to the Dorsal Root Ganglion (DRG) is a minimally invasive day-care treatment, which is gaining significant clinical acceptance in a selective group of patients with pure radicular pain. Greater insights into the immunomodulatory effects of this procedure may help to further optimise its application and find alternative treatment options...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458191/a-novel-neuropilin-1-binding-sequence-in-the-human-t-cell-lymphotropic-virus-type-1-envelope-glycoprotein
#4
Hideki Kusunoki, Toshiyuki Tanaka, Toshiyuki Kohno, Kazuhiko Matsuhashi, Kazuo Hosoda, Kaori Wakamatsu, Isao Hamaguchi
Entry of human T-cell lymphotropic virus type 1 (HTLV-1) into host cells is mainly mediated by interactions between the viral envelope glycoprotein surface unit (SU) and three host receptors: glucose transporter type 1, heparin/heparan sulfate proteoglycan, and neuropilin-1 (Nrp1). Here, we analyzed the interaction between HTLV-1 SU and Nrp1 using nuclear magnetic resonance and isothermal titration calorimetry. We found that two SU peptides, residues 85-94 and residues 304-312, bound directly to the Nrp1 b1 domain with affinities of 7...
February 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29458182/a-direct-gateway-into-the-extracellular-space-unconventional-secretion-of-fgf2-through-self-sustained-plasma-membrane-pores
#5
REVIEW
Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29458149/age-dependent-oxidation-of-extracellular-cysteine-cystine-redox-state-e-h-cys-cyss-in-mouse-lung-fibroblasts-is-mediated-by-a-decline-in-slc7a11-expression
#6
Yuxuan Zheng, Jeffrey D Ritzenthaler, Tom J Burke, Javier Otero, Jesse Roman, Walter H Watson
Aging is associated with progressive oxidation of the extracellular environment. The redox state of human plasma, defined by the concentrations of cysteine (Cys) and cystine (CySS), becomes more oxidized as we age. Recently, we showed that fibroblasts isolated from the lungs of young and old mice retain this differential phenotype; old cells produce and maintain a more oxidizing extracellular redox potential (Eh (Cys/CySS)) than young cells. Microarray analysis identified down-regulation of Slc7a11, the light subunit of the CySS/glutamate transporter, as a potential mediator of age-related oxidation in these cells...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29458130/impact-of-rna-polymerase-i-inhibitor-cx-5461-on-viral-kinase-dependent-and-independent-cytomegalovirus-replication
#7
Kristen N Westdorp, Scott S Terhune
Human cytomegalovirus (HCMV) infections cause congenital birth defects and disease in immunosuppressed individuals. Antiviral compounds can control infection yet their use is restricted due to concerns of toxicity and the emergence of drug resistant strains. We have evaluated the impact of an RNA Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and also activates cellular stress response pathways. The addition of CX-5461 at both early and late stages of the HCMV infection inhibited viral DNA synthesis and virus production...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458124/tryptophan-mediated-dimerization-of-the-tssl-transmembrane-anchor-is-required-for-type-vi-secretion-system-activity
#8
Abdelrahim Zoued, Jean-Pierre Duneau, Eric Durand, Alexandre P España, Laure Journet, Françoise Guerlesquin, Eric Cascales
The Type VI secretion system (T6SS) is a multiprotein complex used by bacteria to deliver effectors into target cells. The T6SS comprises a bacteriophage-like contractile tail structure anchored to the cell envelope by a membrane complex constituted of the TssJ outer membrane lipoprotein and the TssL and TssM inner membrane proteins. TssJ establishes contact with the periplasmic domain of TssM whereas the transmembrane segments of TssM and its cytoplasmic domain interact with TssL. TssL protrudes in the cytoplasm but is anchored by a C-terminal transmembrane helix (TMH)...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458120/major-role-for-trpv1-and-insp3r-in-par-2-elicited-inflammatory-mediator-production-in-differentiated-human-keratinocytes
#9
Olivier Gouin, Killian L'Herondelle, Paul Buscaglia, Christelle Le Gall-Ianotto, Réginald Philippe, Nelig Legoux, Olivier Mignen, Virginie Buhé, Raphael Leschiera, Mehdi Sakka, Nathalie Kerfant, Jean-Luc Carré, Raphaele Le Garrec, Luc Lefeuvre, Nicolas Lebonvallet, Laurent Misery
Proteinase-activated receptor-2 (PAR-2) activation in basal keratinocytes stimulates inflammation via the Ca2+ -dependent production of mediators such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin (TSLP). In this study, we investigated PAR-2 calcium signaling and the consequent production of inflammatory mediators in differentiated human primary keratinocytes (DhPKs). Stimulation with the PAR-2 activating peptide SLIGKV promoted Ca2+ store depletion in both undifferentiated human primary keratinocytes (UhPKs) and DhPKs...
February 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29458116/junk-food-advertising-moderates-the-indirect-effect-of-reward-sensitivity-and-food-consumption-via-the-urge-to-eat
#10
Chloe Kidd, Natalie J Loxton
The current study aimed to identify how underlying individual differences increases vulnerability to television food advertising. In particular, this study examined how reward sensitivity, a biologically-based predisposition to approach rewards (such as appetitive foods) in the environment, influenced participants' vulnerability to television food advertising and subsequent food consumption. Ninety-eight participants were randomly assigned to a cue condition (food cues versus non-food cues) and then viewed a 30 min documentary interrupted by advertising featuring a mix of food and neutral advertising (food cue condition) or only neutral advertising (non-food cue condition)...
February 16, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29458095/rapid-loop-mediated-isothermal-amplification-detection-of-coeliac-disease-risk-alleles
#11
Michael Erlichster, Jason A Tye-Din, Michael D Varney, Efstratios Skafidas, Patrick Kwan
Human leukocyte antigen (HLA) genotyping has become a useful investigation in the diagnostic work-up of coeliac disease (CD), with utility in risk stratification and screening. However, broad application of this technology has been hindered by the cost and time burden of conventional laboratory-based assays. We have developed and validated CD-loop-mediated isothermal amplification (CD-LAMP), a LAMP assay, which enables rapid identification of the signature CD risk genotypes, HLA-DQ2.5, HLA-DQ8, HLA-DQ2.2, and HLA-DQA1*05...
February 16, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29458076/bone-marrow-mesenchymal-stem-cells-bmscs-improved-functional-recovery-of-spinal-cord-injury-partly-by-promoting-axonal-regeneration
#12
REVIEW
Liya Lin, Hefeng Lin, Shi Bai, Lianshun Zheng, Xiaoming Zhang
Spinal cord injury (SCI) disrupts the spinal cord and results in the loss of sensory and motor function below the lesion site. The treatment of SCI became a challenge because the injured neurons fail to axon regenerate and repair after injury. Promoting axonal regeneration plays a key role in the treatment strategies for SCI. It would meet the goal of reconstruction the injured spinal cord and improving the functional recovery. Bone marrow mesenchymal stem cells (BMSCs) are attractive therapeutic potential cell sources for SCI, and it could rebuild the injured spinal cord through neuroprotection, neural regeneration and remyelinating...
February 16, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29458075/lateral-inhibition-in-the-autism-spectrum-an-ssvep-study-of-visual-cortical-lateral-interactions
#13
Abigail Dickinson, Rosanna Gomez, Myles Jones, Vance Zemon, Elizabeth Milne
Circuit level brain dysfunction has been suggested as a common mechanism through which diverse genetic risk factors and neurobiological sequelae lead to the core features of autism spectrum disorder (Geschwind 2009; Port et al. 2014). An important mediator of circuit level brain activity is lateral inhibition, and a number of authors have suggested that lateral inhibition may be atypical in ASD. However, evidence regarding putative atypical lateral connections in ASD is mixed. Here we employed a steady state visual evoked potential (SSVEP) paradigm to further investigate lateral connections within a group of high functioning adults with ASD...
February 16, 2018: Neuropsychologia
https://www.readbyqxmd.com/read/29458061/decreased-mcp-1-ccr2-axis-mediated-chemotactic-effect-of-conjunctival-fibroblasts-after-transdifferentiation-into-myofibroblasts
#14
Utako Tsutsumi-Kuroda, Toshihiro Inoue, Akiko Futakuchi, Kohei Shobayashi, Eri Takahashi, Sachi Kojima, Miyuki Inoue-Mochita, Tomokazu Fujimoto, Hidenobu Tanihara
The purpose of this study is to investigate the change in chemotactic effects of human conjunctival fibroblasts (HConFs) after transdifferentiation into myofibroblasts, and to explore related molecular mechanisms. HConFs were treated with 5 ng/mL transforming growth factor (TGF)-β2 for 48 h to induce transdifferentiation into myofibroblasts. The cytokine concentrations in the conditioned media of HConFs were measured by multiplex bead-based immunoassays. The Boyden chamber assay was used to assess the chemotactic effects using the monocyte cell line, THP-1 cells...
February 16, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29458060/crim1-is-required-for-maintenance-of-the-ocular-lens-epithelium
#15
Oliver H Tam, David Pennisi, Lorine Wilkinson, Melissa H Little, Fatima Wazin, Victor L Wan, Frank J Lovicu
The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respective intracellular signaling pathways are in turn regulated to ensure that the proper lens architecture is maintained. Recent studies have proposed that Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in organogenesis of many tissues, might influence cell adhesion, polarity and proliferation in the lens by regulating integrin-signaling...
February 16, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29458039/differential-contribution-of-calcium-channels-to-%C3%AE-1-adrenoceptor-mediated-contraction-is-responsible-for-diverse-responses-to-cooling-between-rat-tail-and-iliac-arteries
#16
Hirotake Ishida, Shin-Ya Saito, Eita Hishinuma, Tomoaki Kitayama, Tomohisa Ishikawa
Our previous studies have shown that α1 -adrenoceptors, in addition to α2 -adrenoceptors, are involved in enhanced contraction of cutaneous blood vessels during cooling. The present study aimed to elucidate the mechanism underlying it. In tail and iliac arteries isolated from rats, isometric contraction was measured using a myograph and the phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) was quantified by western blotting. The phenylephrine-induced contraction was enhanced by cooling to 24°C in tail arteries, but was suppressed in iliac arteries...
February 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29458026/knockdown-of-fascin-1-expression-suppresses-cell-migration-and-invasion-of-non-small-cell-lung-cancer-by-regulating-the-mapk-pathway
#17
Da Zhao, Tao Zhang, Xiao-Ming Hou, Xiao-Ling Ling
Fascin-1 is a cytoskeletal protein and it can specifically bind to F-actin, it can be abnormally expressed in a variety of solid tumors. Fascin-1 was identified as a factor for poor prognosis in non-small cell lung cancer (NSCLC). However, the relevant molecular mechanisms are not yet fully understood. In this study, the fascin-1 knockdown cells were produced by lentivirus infection, and then cell proliferation, invasion and cell migration assay were used to investigate the role of fascin-1 in NSCLC cells. The MAPK pathway related proteins were determined by western blot...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458024/spinal-cord-specific-deletion-of-the-glutamate-transporter-glt1-causes-motor-neuron-death-in-mice
#18
Kaori Sugiyama, Kohichi Tanaka
Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder characterized by the selective loss of motor neurons. The precise mechanisms that cause the selective death of motor neurons remain unclear, but a growing body of evidence suggests that glutamate-mediated excitotoxicity has been considered to play an important role in the mechanisms of motor neuron degeneration in ALS. Reductions in glutamate transporter GLT1 have been reported in animal models of ALS and the motor cortex and spinal cord of ALS patients...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458023/structural-characterization-of-the-hcov-229e-fusion-core
#19
Wei Zhang, Qianqian Zheng, Mengrong Yan, Xiaobo Chen, Haitao Yang, Weihong Zhou, Zihe Rao
HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458014/topical-delivery-of-l-theanine-ameliorates-tpa-induced-acute-skin-inflammation-via-downregulating-endothelial-pecam-1-and-neutrophil-infiltration-and-activation
#20
Wei-Jie Zeng, Zhi Tan, Xing-Fei Lai, Ya-Nan Xu, Chun-Lin Mai, Jun Zhang, Zhen-Jia Lin, Xian-Guo Liu, Shi-Li Sun, Li-Jun Zhou
l-theanine, the most abundant free amino acid in tea, has been documented to possess many different bioactive properties through oral or intragastrical delivery. However, little is known about the effect of topical delivery of l-theanine on acute inflammation. In the present study, by using 12-O-tetradecanoylphorbol-13-acetate (TPA, 2.5 μg/ear)-induced ear edema model in mice, we first found that single-dose local pretreatment of l-theanine 30 min before TPA time- and dose-dependently suppressed the increases in both skin thickness and weight...
February 16, 2018: Chemico-biological Interactions
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