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https://www.readbyqxmd.com/read/29156533/serotonin-induces-peripheral-antinociception-via-the-opioidergic-system
#1
Danielle Aguiar Diniz, Júlia Alvarenga Petrocchi, Larissa Caldeira Navarro, Tâmara Cristina Souza, Marina Gomes Miranda E Castor, Igor Dimitri Gama Duarte, Thiago Roberto Lima Romero
PURPOSE: Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined. METHODS: The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE2 (2 μg). Serotonin (250 ng), administered locally to the right paw of animals, produces antinociception in this model...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29150945/development-of-an-in-vivo-mouse-model-of-discogenic-low-back-pain
#2
Changgui Shi, Vaskar Das, Xin Li, Ranjan Kc, Sujun Qiu, InSug O-Sullivan, Richard L Ripper, Jeffrey S Kroin, Fackson Mwale, Atiyayein A Wallace, Bingqian Zhu, Lan Zhao, Andre J van Wijnen, Mingliang Ji, Jun Lu, Gina Votta-Velis, Wen Yuan, Hee-Jeong Im
Discogenic Low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there are no in vivo mouse models of DLBP, which restricts research in this field. The aim of this study was to establish a reliable DLBP model in mouse that captures the pathological changes in the disc and allows longitudinal pain testing. The model was generated by puncturing the mouse lumbar discs (L4/5, L5/6, and L6/S1) and removing the nucleus pulposus using a microscalpel under the microscope...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29149607/classifying-drosophila-olfactory-projection-neuron-subtypes-by-single-cell-rna-sequencing
#3
Hongjie Li, Felix Horns, Bing Wu, Qijing Xie, Jiefu Li, Tongchao Li, David J Luginbuhl, Stephen R Quake, Liqun Luo
The definition of neuronal type and how it relates to the transcriptome are open questions. Drosophila olfactory projection neurons (PNs) are among the best-characterized neuronal types: different PN classes target dendrites to distinct olfactory glomeruli, while PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomes of most PN classes and unequivocally mapped transcriptomes to specific olfactory function for six classes...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29146456/is-more-always-better-how-different-doses-of-exercise-after-incomplete-spinal-cord-injury-affects-the-membrane-properties-of-deep-dorsal-horn-interneurons
#4
M M Rank, M P Galea, R Callister, R J Callister
Interneurons in the deep dorsal horn (DDH) of the spinal cord process somatosensory input, and form an important link between upper and lower motoneurons to subsequently shape motor output. Exercise training after SCI is known to improve functional motor recovery, but little is known about the mechanisms within spinal cord neurons that underlie these improvements. Here we investigate how the properties of DDH interneurons are affected by spinal cord injury (SCI) alone, and SCI in combination with different 'doses' of treadmill exercise training (3, 6, and 9wks)...
November 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29143813/ship1-but-not-an-aml-derived-ship1-mutant-suppresses-myeloid-leukemia-growth-in-a-xenotransplantation-mouse-model
#5
M Täger, S Horn, E Latuske, P Ehm, M Schaks, M Nalaskowski, B Fehse, W Fiedler, C Stocking, J Wellbrock, M Jücker
Constitutive activation of the PI3K/AKT signaling pathway is found in ~50-70% of AML patients. The SH2-containing inositol 5-phosphatase 1 (SHIP1) is a negative regulator of PI3K/AKT signaling in hematopoietic cells. SHIP1 knockout mice develop a myeloproliferative syndrome and concomitant deletion of SHIP1 and the tumor suppressor PTEN leads to the development of lethal B-cell lymphomas. In the study presented here, we investigated the role of SHIP1 as a tumor suppressor in myeloid leukemia cells in an in vivo xenograft transplantation model...
November 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29142219/electroacupuncture-attenuates-induction-of-inflammatory-pain-by-regulating-opioid-and-adenosine-pathways-in-mice
#6
Hsien-Yin Liao, Ching-Liang Hsieh, Chun-Ping Huang, Yi-Wen Lin
Although inflammatory pain is a common clinical condition, its mechanisms are still unclear. Electroacupuncture (EA), a well-known method of pain management, may reduce inflammatory pain by regulating neurons, astrocytes, and inflammatory signaling pathways. Injections of complete Freund's adjuvant (CFA), which can initiate cell-mediated inflammatory pain, resulted in significant hyperalgesia, which was subsequently prevented by EA. In CFA-injected mice, a dramatic increase was observed in the expression of the following proteins in the dorsal root ganglion and spinal cord dorsal horn: the astrocytic marker GFAP, S100B, RAGE, pPKCε, COX-2, pERK, and pNFκB...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140923/il-4-mediates-the-analgesia-produced-by-low-intensity-exercise-in-mice-with-neuropathic-pain
#7
Franciane Bobinski, Juliana Maia Teixeira, Kathleen Anne Sluka, Adair Roberto Soares Santos
Peripheral nerve injury (PNI) activates the immune system resulting in increased pro-inflammatory cytokines at the site of injury and in the spinal cord dorsal horn. Exercise modulates the immune system promoting an anti-inflammatory phenotype of macrophages in uninjured muscle, and increases in anti-inflammatory cytokines can promote healing and analgesia. We proposed that PNI will decrease, and treadmill exercise will increase, release of anti-inflammatory cytokines at the site of injury and in the spinal cord...
November 13, 2017: Pain
https://www.readbyqxmd.com/read/29136120/t2-mapping-cardiovascular-magnetic-resonance-identifies-the-presence-of-myocardial-inflammation-in-patients-with-dilated-cardiomyopathy-as-compared-to-endomyocardial-biopsy
#8
M Spieker, E Katsianos, M Gastl, P Behm, P Horn, C Jacoby, B Schnackenburg, P Reinecke, M Kelm, R Westenfeld, F Bönner
Aims: The aim of this study was to determine the value of T2 mapping for the non-invasive assessment of myocardial inflammation in different stages of systolic left ventricular dysfunction in dilated cardiomyopathy (DCM) in comparison with endomyocardial biopsy (EMB). Methods and results: A total of 132 subjects were enrolled between 2013 and 2016 (62 controls and 70 patients with DCM). All patients underwent CMR at 1.5 T and received coronary angiogram and EMB...
November 10, 2017: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/29134656/long-term-dynamic-synaptic-reorganization-after-gabaergic-precursor-cell-transplantation-into-adult-mouse-spinal-cord
#9
Ida J Llewellyn-Smith, Allan I Basbaum, João M Bráz
Transplanting embryonic precursors of GABAergic neurons from the medial ganglionic eminence (MGE) into adult mouse spinal cord ameliorates mechanical and thermal hypersensitivity in peripheral nerve injury models of neuropathic pain. Although Fos and transneuronal tracing studies strongly suggest that integration of MGE-derived neurons into host spinal cord circuits underlies recovery of function, the extent to which there is synaptic integration of the transplanted cells has not been established. Here, we used electron microscopic immunocytochemistry to assess directly integration of GFP-expressing MGE-derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short- (5-6 weeks) or long-term (4-6 months) transplants...
November 13, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29131162/the-3d-orbisims-label-free-metabolic-imaging-with-subcellular-lateral-resolution-and-high-mass-resolving-power
#10
Melissa K Passarelli, Alexander Pirkl, Rudolf Moellers, Dmitry Grinfeld, Felix Kollmer, Rasmus Havelund, Carla F Newman, Peter S Marshall, Henrik Arlinghaus, Morgan R Alexander, Andy West, Stevan Horning, Ewald Niehuis, Alexander Makarov, Colin T Dollery, Ian S Gilmore
We report the development of a 3D OrbiSIMS instrument for label-free biomedical imaging. It combines the high spatial resolution of secondary ion mass spectrometry (SIMS; under 200 nm for inorganic species and under 2 μm for biomolecules) with the high mass-resolving power of an Orbitrap (>240,000 at m/z 200). This allows exogenous and endogenous metabolites to be visualized in 3D with subcellular resolution. We imaged the distribution of neurotransmitters-gamma-aminobutyric acid, dopamine and serotonin-with high spectroscopic confidence in the mouse hippocampus...
November 13, 2017: Nature Methods
https://www.readbyqxmd.com/read/29131016/focal-transplantation-of-aberrant-glial-cells-carrying-the-sod1g93a-mutation-into-rat-spinal-cord-induces-extensive-gliosis
#11
Sofía Ibarburu, Emiliano Trias, Natalia Lago, Hugo Peluffo, Romina Barreto-Núñez, Valentina Varela, Joseph S Beckman, Luis Barbeito
OBJECTIVE: We aimed to determine the potential of aberrant glial cells (AbAs) isolated from the spinal cord of adult SOD1G93A symptomatic rats to induce gliosis and neuronal damage following focal transplantation into the lumbar spinal cord of wild-type rats. METHODS: AbAs were obtained from the spinal cords of SOD1G93A symptomatic rats. One hundred thousand cells were injected using a glass micropipette into the lumbar spinal cords (L3-L5) of syngeneic wild-type adult rats...
November 1, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/29129443/adjuvant-chemotherapy-with-or-without-bevacizumab-in-patients-with-resected-non-small-cell-lung-cancer-e1505-an-open-label-multicentre-randomised-phase-3-trial
#12
Heather A Wakelee, Suzanne E Dahlberg, Steven M Keller, William J Tester, David R Gandara, Stephen L Graziano, Alex A Adjei, Natasha B Leighl, Seena C Aisner, Jan M Rothman, Jyoti D Patel, Mark D Sborov, Sean R McDermott, Roman Perez-Soler, Anne M Traynor, Charles Butts, Tracey Evans, Atif Shafqat, Andrew E Chapman, Samer S Kasbari, Leora Horn, Suresh S Ramalingam, Joan H Schiller
BACKGROUND: Adjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC. METHODS: We did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC...
November 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29127599/cb1-receptors-mediated-inhibition-of-atp-induced-ca-2-i-increase-in-cultured-rat-spinal-dorsal-horn-neurons
#13
Jingdong Long, Xiaolu Lei, Meiyun Chen, Shulei Yang, Tao Sun, Junwei Zeng, Deqian Yu, Hong Tian, Xiaohong Liu
Spinal cannabinoid receptor 1 (CB1R) and purinergic P2X receptors (P2XR) play a critical role in the process of pathological pain. Both CB1R and P2XR are expressed in spinal dorsal horn (DH) neurons. It is not clear whether CB1 receptor activation modulates the function of P2X receptor channels within dorsal horn. For this reason, we observed the effect of CP55940 (cannabinoid receptor agonist) on ATP-induced Ca(2+) mobilization in cultured rat DH neurons. The changes of intracellular calcium concentration ([Ca(2+)]i) were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator...
November 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29122838/soluble-cd80-protein-delays-tumor-growth-and-promotes-tumor-infiltrating-lymphocytes
#14
Lucas A Horn, Tiha M Long, Ryan Atkinson, Virginia Clements, Suzanne Ostrand-Rosenberg
Tumor cells employ various immune suppressive strategies to overcome antitumor immunity. One such method is tumor expression of programmed death ligand-1 (PD-L1), which triggers apoptotic death or anergy upon binding programmed death-1 (PD-1) on T cells. Our previous in vitro cellular studies with human and mouse PD-L1+ tumor cells demonstrated that a soluble form of the costimulatory molecule CD80 prevented PD-L1-mediated immune suppression and restored T-cell activation by binding PD-L1 and blocking interaction with PD-1...
November 9, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29122756/foxp1-expression-is-a-prognostic-biomarker-in-follicular-lymphoma-treated-with-rituximab-containing-regimens
#15
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of seven genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2- and MEF2B-mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in a total of 763 tissue biopsies...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29118923/ddx3-binding-with-ck1%C3%AE%C2%B5-was-closely-related-to-motor-neuron-degeneration-of-als-by-affecting-neurite-outgrowth
#16
Yanchun Chen, Qing Wang, Qiaozhen Wang, Huancai Liu, Fenghua Zhou, Yawen Zhang, Meng Yuan, Chunyan Zhao, Yingjun Guan, Xin Wang
Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive degeneration of motor neurons. The pathogenesis of ALS remains largely unknown. RNA helicase DDX3 is a multifunctional protein involved in several steps of gene expression. Casein kinase 1ε (CK1ε) is an important signal molecule of Wnt signaling pathway and is closely related to neurite growth. However, the roles of DDX3 and CK1ε in the pathogenesis of ALS remain unclear. In this study, we first investigated the expression of DDX3 and CK1ε in the spinal cord of SOD1-G93A ALS transgenic mice using RT-PCR, Western blot and immunohistochemical technique...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118920/combination-therapy-with-extracorporeal-shock-wave-and-melatonin-markedly-attenuated-neuropathic-pain-in-rat
#17
Kuan-Hung Chen, Chien-Hui Yang, Christopher Glenn Wallace, Chung-Ren Lin, Chia-Kai Liu, Tsung-Cheng Yin, Tien-Hung Huang, Yi-Ling Chen, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29114369/bimelic-symmetric-hirayama-disease-spectrum-of-magnetic-resonance-imaging-findings-and-comparative-evaluation-with-classical-monomelic-amyotrophy-and-other-motor-neuron-disease
#18
Deb Kumar Boruah, Shantiranjan Sanyal, Arjun Prakash, Sashidhar Achar, Dhabal D Dhingani, Binod Sarma
Background: The aim of the study was to evaluate the magnetic resonance imaging (MRI) findings in bilateral symmetrical Hirayama disease and find out MRI features which are probably more indicative of symmetrical Hirayama disease, thereby help in differentiating this entity from other motor neuron disease (MND). Methods: This prospective as well as retrospective study was carried out from December 2010 to September 2016 in a tertiary care center of northeast India on 92 patients with Hirayama disease. Only 19 patients having bilateral symmetric upper limb involvement at the time of presentation were included in this study sample...
July 6, 2017: Iranian Journal of Neurology
https://www.readbyqxmd.com/read/29113871/oxidative-stress-and-dietary-phytochemicals-role-in-cancer-chemoprevention-and-treatment
#19
Shireen Chikara, Lokesh Dalasanur Nagaprashantha, Jyotsana Singhal, David Horne, Sanjay Awasthi, Sharad S Singhal
Several epidemiological observations have shown an inverse relation between consumption of plant-based foods, rich in phytochemicals, and incidence of cancer. Phytochemicals, secondary plant metabolites, via their antioxidant property play a key role in cancer chemoprevention by suppressing oxidative stress-induced DNA damage. In addition, they modulate several oxidative stress-mediated signaling pathways through their anti-oxidant effects, and ultimately protect cells from undergoing molecular changes that trigger carcinogenesis...
November 4, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29113403/a-phase-2-open-label-multi-center-study-of-amuvatinib-in-combination-with-platinum-etoposide-chemotherapy-in-platinum-refractory-small-cell-lung-cancer-patients
#20
Lauren Averett Byers, Leora Horn, Jitendra Ghandi, Goetz Kloecker, Taofeek Owonikoko, Saiama Naheed Waqar, Maciej Krzakowski, Robert J Cardnell, Junya Fujimoto, Pietro Taverna, Mohammad Azab, David Ross Camidge
Background: Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. Methods: This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days...
October 6, 2017: Oncotarget
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