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https://www.readbyqxmd.com/read/28933201/glioma-and-microenvironment-dual-targeted-nanocarrier-for-improved-antiglioblastoma-efficacy
#1
Xiuzhen Wang, Qing Zhang, Lingyan Lv, Junjie Fu, Yan Jiang, Hongliang Xin, Qizheng Yao
Drug delivery systems based on nanoparticles (nano-DDS) have aroused attentions for the treatment of glioblastoma (GBM), the most malignant brain cancer with a dismal prognosis. However, there are still numerous unmet challenges for traditional nano-DDS, such as the poor nanoparticle penetration, short retention in the GBM parenchyma and low glioma targeting ability. Herein, we used Pep-1 and CREKA peptides to construct a novel multifunctional GBM targeting nano-DDS (PC-NP). Pep-1 was used to overcome the blood-brain tumor barrier (BBTB) and home to glioma cells via interleukin-13 receptor-α2-mediated endocytosis, and CREKA was used to bind to fibrin-fibronectin complexes abundantly expressed in tumor microenvironment for enhanced retention in the GBM...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28932225/expression-and-function-of-the-cholinergic-system-in-immune-cells
#2
REVIEW
Takeshi Fujii, Masato Mashimo, Yasuhiro Moriwaki, Hidemi Misawa, Shiro Ono, Kazuhide Horiguchi, Koichiro Kawashima
T and B cells express most cholinergic system components-e.g., acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Using ChAT(BAC)-eGFP transgenic mice, ChAT expression has been confirmed in T and B cells, dendritic cells, and macrophages. Moreover, T cell activation via T-cell receptor/CD3-mediated pathways upregulates ChAT mRNA expression and ACh synthesis, suggesting that this lymphocytic cholinergic system contributes to the regulation of immune function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28931433/role-of-gabaa-receptors-in-alcohol-use-disorders-suggested-by-chronic-intermittent-ethanol-cie-rodent-model
#3
REVIEW
Richard W Olsen, Jing Liang
GABAergic inhibitory transmission is involved in the acute and chronic effects of ethanol on the brain and behavior. One-dose ethanol exposure induces transient plastic changes in GABAA receptor subunit levels, composition, and regional and subcellular localization. Rapid down-regulation of early responder δ subunit-containing GABAA receptor subtypes mediating ethanol-sensitive tonic inhibitory currents in critical neuronal circuits corresponds to rapid tolerance to ethanol's behavioral responses. Slightly slower, α1 subunit-containing GABAA receptor subtypes mediating ethanol-insensitive synaptic inhibition are down-regulated, corresponding to tolerance to additional ethanol behaviors plus cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids, especially sedative-hypnotic effects...
September 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28929924/the-search-for-a-subtype-selective-pet-imaging-agent-for-the-gabaa-receptor-complex-evaluation-of-the-radiotracer-11-c-ado-in-nonhuman-primates
#4
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABAA, GABAB, and GABAC groups. The various GABAA subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28923942/identification-of-sialic-acid-binding-function-for-the-middle-east-respiratory-syndrome-coronavirus-spike-glycoprotein
#5
Wentao Li, Ruben J G Hulswit, Ivy Widjaja, V Stalin Raj, Ryan McBride, Wenjie Peng, W Widagdo, M Alejandra Tortorici, Brenda van Dieren, Yifei Lang, Jan W M van Lent, James C Paulson, Cornelis A M de Haan, Raoul J de Groot, Frank J M van Kuppeveld, Bart L Haagmans, Berend-Jan Bosch
Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1(A) through S1(D) Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1(B) We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia)...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28915667/assessment-of-near-infrared-fluorophores-to-study-the-biodistribution-and-tumor-targeting-of-an-il13-receptor-%C3%AE-2-antibody-by-fluorescence-molecular-tomography
#6
Parul Gupta, Jo-Ann Wentland, Mauricio Leal, Dangshe Ma, Rachel Roach, Antonio Esparza, Lindsay King, Mary E Spilker, Cedo Bagi, Christopher T Winkelmann, Anand Giddabasappa
Non-invasive imaging using radiolabels is a common technique used to study the biodistribution of biologics. Due to the limited shelf-life of radiolabels and the requirements of specialized labs, non-invasive optical imaging is an attractive alternative for preclinical studies. Previously, we demonstrated the utility of fluorescence molecular tomography (FMT) an optical imaging modality in evaluating the biodistribution of antibody-drug conjugates. As FMT is a relatively new technology, few fluorophores have been validated for in vivo imaging...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914648/dexmedetomidine-maintains-its-direct-cardioprotective-effect-against-ischemia-reperfusion-injury-in-hypertensive-hypertrophied-myocardium
#7
Yusuke Yoshikawa, Naoyuki Hirata, Ryoichi Kawaguchi, Yasuyuki Tokinaga, Michiaki Yamakage
BACKGROUND: Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia/reperfusion injury through endothelial nitric oxide synthase (eNOS) phosphorylation via α2-adrenoreceptor (α2-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac α2-AR and the I1 imidazoline receptor (I1R) were examined. METHODS: Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia...
September 12, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28905526/transmission-and-immunopathology-of-the-avian-influenza-virus-a-anhui-1-2013-h7n9-human-isolate-in-three-commonly-commercialized-avian-species
#8
B Vidaña, R Dolz, N Busquets, A Ramis, R Sánchez, R Rivas, R Valle, I Cordón, D Solanes, J Martínez, N Majó
H7N9 virus infection is a global concern, given that it can cause severe infection and mortality in humans. However, the understanding of H7N9 epidemiology, animal reservoir species and zoonotic risk remains limited. This work evaluates the pathogenicity, transmissibility and local innate immune response of three avian species harbouring different respiratory distribution of α2,6 and α2,3 SA receptors. Muscovy ducks, European quails and SPF chickens were intranasally inoculated with 10(5) embryo infectious dose (EID)50 of the human H7N9 (A/Anhui/1/2013) influenza isolate...
September 14, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28901501/mtor-inhibition-reduces-growth-and-adhesion-of-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#9
Tobias Engl, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Frederik Roos, Wael Khoder, Wolf O Bechstein, Karen Nelson, Igor Tsaur, Axel Haferkamp, Roman A Blaheta
Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and β adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900138/adaptation-of-influenza-a-h7n9-virus-in-primary-human-airway-epithelial-cells
#10
Daniel Tsung-Ning Huang, Chun-Yi Lu, Ya-Hui Chi, Wan-Ling Li, Luan-Yin Chang, Mei-Ju Lai, Jin-Shing Chen, Wen-Ming Hsu, Li-Min Huang
Influenza A (H7N9) is an emerging zoonotic pathogen with pandemic potential. To understand its adaptation capability, we examined the genetic changes and cellular responses following serial infections of A (H7N9) in primary human airway epithelial cells (hAECs). After 35 serial passages, six amino acid mutations were found, i.e. HA (R54G, T160A, Q226L, H3 numbering), NA (K289R, or K292R for N2 numbering), NP (V363V/I) and PB2 (L/R332R). The mutations in HA enabled A(H7N9) virus to bind with higher affinity (from 39...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889125/brimonidine-protects-auditory-hair-cells-from-in-vitro-induced-toxicity-of-gentamicin
#11
Maurizio Cortada, Soledad Levano, Daniel Bodmer
Brimonidine, an alpha-2 adrenergic receptor (α2-AR) agonist, has neuroprotective effects in the visual system and in spiral ganglion neurons. Auditory hair cells (HCs) express all 3 α2-AR subtypes, but their roles in HCs remain unknown. This study investigated the effects of brimonidine on auditory HCs that were also exposed to gentamicin, which is toxic to HCs. Organ of Corti explants were exposed to gentamicin in the presence or absence of brimonidine, and the α2-AR protein expression levels and Erk1/2 and Akt phosphorylation levels were determined...
September 9, 2017: Audiology & Neuro-otology
https://www.readbyqxmd.com/read/28883754/the-activation-of-%C3%AE-2-adrenergic-receptor-in-the-spinal-cord-lowers-sepsis-induced-mortality
#12
Sung-Su Kim, Soo-Hyun Park, Jae-Ryung Lee, Jun-Sub Jung, Hong-Won Suh
The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; 27 µg/27 µl) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine (5 µg/5 µl) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect...
September 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28882570/taurine-restores-the-exploratory-behavior-following-alcohol-withdrawal-and-decreases-bdnf-mrna-expression-in-the-frontal-cortex-of-chronic-alcohol-treated-rats
#13
Alana Witt Hansen, Felipe Borges Almeida, Solange Bandiera, Rianne Remus Pulcinelli, Ana Luiza Rodrigues Fragoso, Ricardo Schneider, Helena Maria Tannhauser Barros, Rosane Gomez
Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABAAR) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABAAR α2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal...
September 5, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28878121/a-tcr%C3%AE-framework-centered-codon-shapes-a-biased-t-cell-repertoire-through-direct-mhc-and-cdr3%C3%AE-interactions
#14
Kristin Støen Gunnarsen, Lene Støkken Høydahl, Louise Fremgaard Risnes, Shiva Dahal-Koirala, Ralf Stefan Neumann, Elin Bergseng, Terje Frigstad, Rahel Frick, M Fleur du Pré, Bjørn Dalhus, Knut Ea Lundin, Shuo-Wang Qiao, Ludvig M Sollid, Inger Sandlie, Geir Åge Løset
Selection of biased T cell receptor (TCR) repertoires across individuals is seen in both infectious diseases and autoimmunity, but the underlying molecular basis leading to these shared repertoires remains unclear. Celiac disease (CD) occurs primarily in HLA-DQ2.5+ individuals and is characterized by a CD4+ T cell response against gluten epitopes dominated by DQ2.5-glia-α1a and DQ2.5-glia-α2. The DQ2.5-glia-α2 response recruits a highly biased TCR repertoire composed of TRAV26-1 paired with TRBV7-2 harboring a semipublic CDR3β loop...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28877402/effects-of-s-38093-an-antagonist-inverse-agonist-of-histamine-h3-receptors-in-models-of-neuropathic-pain-in-rats
#15
T Chaumette, E Chapuy, E Berrocoso, M Llorca-Torralba, L Bravo, J A Mico, M Chalus, A Eschalier, D Ardid, F Marchand, A Sors
BACKGROUND: Histamine H3 receptors are mainly expressed on CNS neurons, particularly along the nociceptive pathways. The potential involvement of these receptors in pain processing has been suggested using H3 receptor inverse agonists. METHODS: The antinociceptive effect of S 38093, a novel inverse agonist of H3 receptors, has been evaluated in several neuropathic pain models in rat and compared with those of gabapentin and pregabalin. RESULTS: While S 38093 did not change vocalization thresholds to paw pressure in healthy rats, it exhibited a significant antihyperalgesic effect in the Streptozocin-induced diabetic (STZ) neuropathy model after acute and chronic administration and, in the chronic constriction injury (CCI) model only after chronic administration, submitted to the paw-pressure test...
September 6, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28855875/therapeutic-potential-of-selectively-targeting-the-%C3%AE-2c-adrenoceptor-in-cognition-depression-and-schizophrenia-new-developments-and-future-perspective
#16
REVIEW
Madeleine Monique Uys, Mohammed Shahid, Brian Herbert Harvey
α2A- and α2C-adrenoceptors (ARs) are the primary α2-AR subtypes involved in central nervous system (CNS) function. These receptors are implicated in the pathophysiology of psychiatric illness, particularly those associated with affective, psychotic, and cognitive symptoms. Indeed, non-selective α2-AR blockade is proposed to contribute toward antidepressant (e.g., mirtazapine) and atypical antipsychotic (e.g., clozapine) drug action. Both α2C- and α2A-AR share autoreceptor functions to exert negative feedback control on noradrenaline (NA) release, with α2C-AR heteroreceptors regulating non-noradrenergic transmission (e...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28846105/c-reactive-protein-binds-to-integrin-%C3%AE-2-and-fc%C3%AE-receptor-i-leading-to-breast-cell-adhesion-and-breast-cancer-progression
#17
E-S Kim, S Y Kim, M Koh, H-M Lee, K Kim, J Jung, H S Kim, W K Moon, S Hwang, A Moon
C-reactive protein (CRP) is an acute phase protein synthesized upon the inflammatory responses, associated with breast cancer. The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. The present study investigated the role of CRP in the adhesive phenotype of breast cells and the underlying mechanisms. Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28843008/sevoflurane-neurotoxicity-in-neonatal-rats-is-related-to-an-increase-in-the-gabaa-r-%C3%AE-1-gabaa-r-%C3%AE-2-ratio
#18
Si-Ning Xie, Hong Ye, Jun-Fa Li, Li-Xin An
Exposure of neonatal rat to sevoflurane leads to neurodegeneration and deficits of spatial learning and memory in adulthood. However, the underlying mechanisms remain unclear. The type A γ-aminobutyric acid receptor (GABAA R) is a target receptor for sevoflurane. The present study intends to investigate the changes in GABAA R α1/α2 expression and its relationship with the neurotoxicity effect due to sevoflurane in neonatal rats. After a dose-response curve was constructed to determine minimum alveolar concentration (MAC) and safety was guaranteed in our 7-day-old neonatal rat pup mode, we conducted two studies among the following groups: (A) the control group; (B) the sham anesthesia group; and (C) the sevoflurane anesthesia group and all three groups were treated in the same way as the model...
August 26, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28836008/alpha2-adrenoceptors-in-adrenomedullary-chromaffin-cells-functional-role-and-pathophysiological-implications
#19
REVIEW
Antonio R Artalejo, Luis Alcides Olivos-Oré
Chromaffin cells from the adrenal medulla participate in stress responses by releasing catecholamines into the bloodstream. Main control of adrenal catecholamine secretion is exerted both neurally (by the splanchnic nerve fibers) and humorally (by corticosteroids, circulating noradrenaline, etc.). It should be noted, however, that secretory products themselves (catecholamines, ATP, opioids, ascorbic acid, chromogranins) could also influence the secretory response in an autocrine/paracrine manner. This form of control is activity-dependent and can be either inhibitory or excitatory...
August 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28832645/microparticle-and-anti-influenza-activity-in-human-respiratory-secretion
#20
Ornpreya Suptawiwat, Kanyarat Ruangrung, Chompunuch Boonarkart, Pilaipan Puthavathana, Kittipong Maneechotesuwan, Komgrid Charngkaew, Nusara Chomanee, Prasert Auewarakul
Respiratory secretions, such as saliva and bronchoalveolar fluid, contain anti-influenza activity. Multiple soluble factors have been described that exert anti-influenza activity and are believed to be responsible for the anti-influenza activity in respiratory secretions. It was previously shown that a bronchial epithelial cell culture could produce exosome-like particles with anti-influenza activity. Whether such extracellular vesicles in respiratory secretions have anti-influenza activity is unknown. Therefore, we characterized bronchoalveolar lavage fluid and found microparticles, which mostly stained positive for epithelial cell markers and both α2,3- and α2,6-linked sialic acid...
2017: PloS One
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