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https://www.readbyqxmd.com/read/28440712/gelatin-albumin-hybrid-nanoparticles-as-matrix-metalloproteinases-degradable-delivery-systems-for-breast-cancer-therapy
#1
Vahid Heravi Shargh, Hubert Hondermarck, Mingtao Liang
AIM: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA) inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects in breast cancer. METHODS: Gel-Alb-GNF HNPs were prepared using a pH-controlled complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF-5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of subtype-specific breast cancer cell lines...
April 25, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28416686/ngf-trka-signaling-in-sensory-nerves-is-required-for-skeletal-adaptation-to-mechanical-loads-in-mice
#2
Ryan E Tomlinson, Zhi Li, Zhu Li, Liliana Minichiello, Ryan C Riddle, Arun Venkatesan, Thomas L Clemens
Sensory nerves emanating from the dorsal root extensively innervate the surfaces of mammalian bone, a privileged location for the regulation of biomechanical signaling. Here, we show that NGF-TrkA signaling in skeletal sensory nerves is an early response to mechanical loading of bone and is required to achieve maximal load-induced bone formation. First, the elimination of TrkA signaling in mice harboring mutant TrkA(F592A) alleles was found to greatly attenuate load-induced bone formation induced by axial forelimb compression...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28404842/an-immortalized-human-dorsal-root-ganglia-cell-line-provides-a-novel-context-to-study-herpes-simplex-virus-type-1-latency-and-reactivation
#3
Nikki M Thellman, Carolyn Botting, Zachary Madaj, Steven J Triezenberg
A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-myc oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28398601/antidepressant-imipramine-protects-bupivacaine-induced-neurotoxicity-in-dorsal-root-ganglion-neurons-through-co-activation-of-trka-and-trkb
#4
Jianrong Guo, Huan Wang, Qiang Tao, Shiyu Sun, Li Liu, Jianping Zhang, Dawei Yang
PURPOSE: In our work, we used an in vitro culture model to investigate whether antidepressant imipramine (Ip) may protect bupivacaine (Bv)-induced neurotoxicity in mouse dorsal root ganglion (DRG). METHODS: Adult mouse DRG was treated with 5 mM Bv in vitro to induce neurotoxicity. DRG was then pre-treated with Ip, prior to Bv, to examine its effects on protecting Bv-induced DRG apoptosis and neurite degeneration. Ip-induced dynamic changes in Trk receptors, including TrkA/B/C and phosphor (p-)TrkA/B/C, were examined by qPCR and western blot...
April 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28395118/etv6-runx1-like-acute-lymphoblastic-leukemia-a-novel-b-cell-precursor-leukemia-subtype-associated-with-the-cd27-cd44-immunophenotype
#5
Marketa Zaliova, Michaela Kotrova, Silvia Bresolin, Jan Stuchly, Jan Stary, Ondrej Hrusak, Geertruy Te Kronnie, Jan Trka, Jan Zuna, Martina Vaskova
We have shown previously that ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is distinguishable from other ALL subtypes by CD27(p) °(s) /CD44(l) °(w-neg) immunophenotype. During diagnostic immunophenotyping of 573 childhood B-cell precursor ALL (BCP-ALL), we identified eight cases with this immunophenotype among "B-other ALL" (BCP-ALL cases negative for routinely tested chromosomal/genetic aberrations). We aimed to elucidate whether these cases belong to the recently described ETV6/RUNX1-like ALL defined by the ETV6/RUNX1-specific gene expression profile, harboring concurrent ETV6 and IKZF1 lesions...
April 10, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28383489/sulfated-hetero-polysaccharides-protect-sh-sy5y-cells-from-h%C3%A2-o%C3%A2-induced-apoptosis-by-affecting-the-pi3k-akt-signaling-pathway
#6
Jing Wang, Huaide Liu, Xue Zhang, Xinpeng Li, Lihua Geng, Hong Zhang, Quanbin Zhang
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H₂O₂-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect...
April 6, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28380365/retrogradely-transported-trka-endosomes-signal-locally-within-dendrites-to-maintain-sympathetic-neuron-synapses
#7
Kathryn M Lehigh, Katherine M West, David D Ginty
Sympathetic neurons require NGF from their target fields for survival, axonal target innervation, dendritic growth and formation, and maintenance of synaptic inputs from preganglionic neurons. Target-derived NGF signals are propagated retrogradely, from distal axons to somata of sympathetic neurons via TrkA signaling endosomes. We report that a subset of TrkA endosomes that are transported from distal axons to cell bodies translocate into dendrites, where they are signaling competent and move bidirectionally, in close proximity to synaptic protein clusters...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28360840/impaired-ngf-trka-signaling-causes-early-ad-linked-presynaptic-dysfunction-in-cholinergic-primary-neurons
#8
Valentina Latina, Silvia Caioli, Cristina Zona, Maria T Ciotti, Giuseppina Amadoro, Pietro Calissano
Alterations in NGF/TrkA signaling have been suggested to underlie the selective degeneration of the cholinergic basal forebrain neurons occurring in vivo in AD (Counts and Mufson, 2005; Mufson et al., 2008; Niewiadomska et al., 2011) and significant reduction of cognitive decline along with an improvement of cholinergic hypofunction have been found in phase I clinical trial in humans affected from mild AD following therapeutic NGF gene therapy (Tuszynski et al., 2005, 2015). Here, we show that the chronic (10-12 D...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28360836/genetic-tracing-of-cav3-2-t-type-calcium-channel-expression-in-the-peripheral-nervous-system
#9
Yinth A Bernal Sierra, Julia Haseleu, Alexey Kozlenkov, Valérie Bégay, Gary R Lewin
Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28347639/neurite-outgrowth-in-cultured-mouse-pelvic-ganglia-effects-of-neurotrophins-and-bladder-tissue
#10
Mari Ekman, Baoyi Zhu, Karl Swärd, Bengt Uvelius
Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro...
March 18, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28338624/nerve-growth-factor-signaling-from-membrane-microdomains-to-the-nucleus-differential-regulation-by-caveolins
#11
Ambre Spencer, Lingli Yu, Vincent Guili, Florie Reynaud, Yindi Ding, Ji Ma, Jérôme Jullien, David Koubi, Emmanuel Gauthier, David Cluet, Julien Falk, Valérie Castellani, Chonggang Yuan, Brian B Rudkin
Membrane microdomains or "lipid rafts" have emerged as essential functional modules of the cell, critical for the regulation of growth factor receptor-mediated responses. Herein we describe the dichotomy between caveolin-1 and caveolin-2, structural and regulatory components of microdomains, in modulating proliferation and differentiation. Caveolin-2 potentiates while caveolin-1 inhibits nerve growth factor (NGF) signaling and subsequent cell differentiation. Caveolin-2 does not appear to impair NGF receptor trafficking but elicits prolonged and stronger activation of MAPK (mitogen-activated protein kinase), Rsk2 (ribosomal protein S6 kinase 2), and CREB (cAMP response element binding protein)...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335430/a-review-on-ubiquitination-of-neurotrophin-receptors-facts-and-perspectives
#12
REVIEW
Julia Sánchez-Sánchez, Juan Carlos Arévalo
Ubiquitination is a reversible post-translational modification involved in a plethora of different physiological functions. Among the substrates that are ubiquitinated, neurotrophin receptors (TrkA, TrkB, TrkC, and p75(NTR)) have been studied recently. TrkA is the most studied receptor in terms of its ubiquitination, and different E3 ubiquitin ligases and deubiquitinases have been implicated in its ubiquitination, whereas not much is known about the other neurotrophin receptors aside from their ubiquitination...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332364/potential-antitumor-activity-of-sim-89-in-non-small-cell-lung-cancer-cells
#13
Jun Pei, Tianqing Chu, Minhua Shao, Jiajun Teng, Huifang Sha, Aiqing Gu, Rong Li, Jialin Qian, Weifeng Mao, Ying Li, Baohui Han
PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z'-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28331056/monitoring-of-childhood-all-using-bcr-abl1-genomic-breakpoints-identifies-a-subgroup-with-cml-like-biology
#14
Lenka Hovorkova, Marketa Zaliova, Nicola C Venn, Kirsten Bleckmann, Marie Trkova, Eliska Potuckova, Martina Vaskova, Jana Linhartova, Katerina Machova Polakova, Eva Fronkova, Walter Muskovic, Jodie E Giles, Peter J Shaw, Gunnar Cario, Rosemary Sutton, Jan Stary, Jan Trka, Jan Zuna
We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, over 20% of children (25% [8/32] with minor and 12.5% [1/8] with Major-BCR-ABL1 variants in the consecutive cohorts) had significantly (>1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28327516/an-extract-from-shrimp-processing-by-products-protects-sh-sy5y-cells-from-neurotoxicity-induced-by-a%C3%AE-25-35
#15
Yongping Zhang, Guangling Jiao, Cai Song, Shelly Gu, Richard E Brown, Junzeng Zhang, Pingcheng Zhang, Jacques Gagnon, Steven Locke, Roumiana Stefanova, Claude Pelletier, Yi Zhang, Hongyu Lu
Increased evidence suggests that marine unsaturated fatty acids (FAs) can protect neurons from amyloid-β (Aβ)-induced neurodegeneration. Nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and gas chromatography (GC) assays showed that the acetone extract 4-2A obtained from shrimp Pandalus borealis industry processing wastes contained 67.19% monounsaturated FAs and 16.84% polyunsaturated FAs. The present study evaluated the anti-oxidative and anti-inflammatory effects of 4-2A in Aβ25-35-insulted differentiated SH-SY5Y cells...
March 22, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28326938/mechanisms-of-nerve-growth-factor-signaling-in-bone-nociceptors-and-in-an-animal-model-of-inflammatory-bone-pain
#16
Sara Nencini, Mitchell Ringuet, Dong-Hyun Kim, Yu-Jen Chen, Claire Greenhill, Jason J Ivanusic
Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28321769/n-propargyl-caffeamide-paca-ameliorates-dopaminergic-neuronal-loss-and-motor-dysfunctions-in-mptp-mouse-model-of-parkinson-s-disease-and-in-mpp-induced-neurons-via-promoting-the-conversion-of-prongf-to-ngf
#17
Dan Luo, Jia Zhao, Yuanyuan Cheng, Simon Ming-Yuen Lee, Jianhui Rong
Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days...
March 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28320270/role-of-nerve-growth-factor-in-plasticity-of-forebrain-cholinergic-neurons
#18
REVIEW
N K Isaev, E V Stelmashook, E E Genrikhs
Neuronal plastic rearrangements during the development and functioning of neurons are largely regulated by trophic factors, including nerve growth factor (NGF). NGF is also involved in the pathogenesis of Alzheimer's disease. In the brain, NGF is produced in structures innervated by basal forebrain cholinergic neurons and retrogradely transported along the axons to the bodies of cholinergic neurons. NGF is essential for normal development and functioning of the basal forebrain; it affects formation of the dendritic tree and modulates the activities of choline acetyltransferase and acetylcholinesterase in basal forebrain neurons...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319380/evaluation-and-characterization-of-trk-kinase-inhibitors-for-the-treatment-of-pain-reliable-binding-affinity-predictions-from-theory-and-computation
#19
Shunzhou Wan, Agastya P Bhati, Sarah Skerratt, Kiyoyuki Omoto, Veerabahu Shanmugasundaram, Sharan K Bagal, Peter V Coveney
Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibility as well as the long turnaround times required to obtain results. Herein we report on a collaborative study that compares tropomyosin receptor kinase A (TrkA) binding affinity predictions using two recently formulated fast computational approaches, namely, Enhanced Sampling of Molecular dynamics with Approximation of Continuum Solvent (ESMACS) and Thermodynamic Integration with Enhanced Sampling (TIES), to experimentally derived TrkA binding affinities for a set of Pfizer pan-Trk compounds...
April 24, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28315978/the-hallucinogen-2-5-dimethoxy-4-iodoamphetamine-hydrochloride-activates-neurotrophin-receptors-in-a-neuronal-cell-line-and-promotes-neurites-extension
#20
Zoya Marinova, Susanne Walitza, Edna Grünblatt
Decreased neurotrophic factors expression and neurotrophin receptors signalling have repeatedly been reported in association with stress, depression, and neurodegenerative disorders. We have previously identified the hallucinogen 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) as protective against trophic deprivation-induced cytotoxicity in human neuroblastoma SK-N-SH cells and established the dependence of this effect on the 5-HT2A receptor, tyrosine kinases activity, and the extracellular signal-regulated kinase pathway...
March 18, 2017: Journal of Neural Transmission
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