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https://www.readbyqxmd.com/read/28110056/current-knowledge-and-management-of-hypersensitivity-reactions-to-monoclonal-antibodies
#1
Matthieu Picard, Violeta Régnier Galvão
Hypersensitivity reactions (HSRs) to monoclonal antibodies (mAbs) are increasingly frequent as this class of therapeutic agents is rapidly expanding. Immediate and nonimmediate HSRs have been reported with mAbs. Immediate HSRs can be explained by 3 main mechanisms: cytokine release syndrome, IgE-mediated, and IgG-mediated reactions. Importantly, IgE-mediated reactions can occur on first exposure due to preformed specific IgEs, as shown for cetuximab. Almost all patients with an immediate HSR can be safely re-exposed either through desensitization or challenge depending on the severity and mechanism of the initial reaction...
January 18, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28109571/in%C3%A2-vivo-tissue-engineering-of-human%C3%A2-airways
#2
Emmanuel Martinod, Joseph Paquet, Hervé Dutau, Dana M Radu, Morad Bensidhoum, Sébastien Abad, Yurdagül Uzunhan, Eric Vicaut, Hervé Petite
BACKGROUND: Airway transplantation remains a major challenge in thoracic surgery. Based on our previous laboratory work, we developed the techniques required to bioengineer a tracheal substitute in vivo using cryopreserved aortic allografts as biological matrices (Replacement of the Airways and/or the Pulmonary Vessels Using a Cryopreserved Arterial Allograft [TRACHEOBRONCART] Study, NCT01331863). We present here 2 patients who had a definitive tracheostomy for complex laryngotracheal stenoses refractory to conventional therapy...
January 18, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28109401/melanoma-last-call-for-radiotherapy
#3
REVIEW
Sophie Espenel, Alexis Vallard, Chloé Rancoule, Max-Adrien Garcia, Jean-Baptiste Guy, Cyrus Chargari, Eric Deutsch, Nicolas Magné
Melanoma is traditionally considered to be a radioresistant tumor. However, radiotherapy and immunotherapy latest developments might upset this radiobiological dogma. Stereotactic radiotherapy allows high dose per fraction delivery, with high dose rate. More DNA lethal damages, less sublethal damages reparation, endothelial cell apoptosis, and finally clonogenic cell dysfunction are produced, resulting in improved local control. Radiotherapy can also enhance immune responses, inducing neoantigens formation, tumor antigen presentation, and cytokines release...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28109141/-hydrogen-rich-saline-attenuates-hyperalgesia-and-reduces-cytokines-in-rats-with-post-herpetic-neuralgia-via-activating-autophagy
#4
Hongtao Ma, Hongguang Chen, Aili Dong, Yanyan Wang, Yingxue Bian, Keliang Xie
Objective To investigate the role of autophagy in hydrogen-rich saline attenuating post-herpetic neuralgia (PHN) in rats. Methods A total of 100 male SD rats were randomly divided into the five groups (n=20): control group, PHN group, PHN group treated with hydrogen-rich saline (PHN-H2 group), PHN group treated with hydrogen-rich saline and 3-MA (PHN-H2-3-MA group), PHN group treated with hydrogen-rich saline and rapamycin (PHN-H2-Rap group). PHN models were established by varicella-zoster virus (VZV) inoculation...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28109101/-fgf-2-pela-bmp-2-microcapsule-scaffold-promotes-osteogenic-differentiation-of-rat-periosteum-derived-stem-cells-in-vitro
#5
Jie Yin, Su-Jun Qiu, Jun-Huai Gao, Sheng-Li Zhao, Shao-Xiong Min
OBJECTIVE: To observe the effect of a microencapsule scaffold capable of sustained release of fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) in promoting the osteogenic differentiation of rat periosteum-derived stem cells (PDSCs) in vitro. METHODS: PDSCs from 4-week-old SD rats, after identification of the surface markers using flow cytometry, were induced to differentiate into osteoblast, chondroblast, and adipocyte lineages. The differentiated cells were verified by staining with Alizarin red, toluidine blue, alcian blue, oil red O and by immunofluorescence assay...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#6
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28108544/the-interplay-between-neutrophils-and-cd8-t-cells-improves-survival-in-human-colorectal-cancer
#7
Valeria Governa, Emanuele Trella, Valentina Mele, Luigi Tornillo, Francesca Amicarella, Eleonora Cremonesi, Maunele Giuseppe Muraro, Hui Xu, Raoul Droeser, Silvio Raffael Däster, Martin Bolli, Raffaele Rosso, Daniel Oertli, Serenella Eppenberger-Castori, Luigi Terracciano, Giandomenica Iezzi, Giulio C Spagnoli
PURPOSE: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer (CRC). Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes and functional features of CRC infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells. EXPERIMENTAL DESIGN: CD66b+ and CD8+ cell infiltration was analyzed by immunohistochemistry on a tissue microarray including >650 evaluable CRC samples...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108469/blood-rna-biomarkers-in-prodromal-park4-and-rem-sleep-behavior-disorder-show-role-of-complexin-1-loss-for-risk-of-parkinson-s-disease
#8
Suna Lahut, Suzana Gispert, Özgür Ömür, Candan Depboylu, Kay Seidel, Jorge Antolio Domínguez-Bautista, Nadine Brehm, Hülya Tireli, Karl Hackmann, Caroline Pirkevi, Barbara Leube, Vincent Ries, Kerstin Reim, Nils Brose, Wilfred F den Dunnen, Madrid Johnson, Zsuzsanna Wolf, Marc Schindewolf, Wiebke Schrempf, Kathrin Reetz, Peter Young, David Vadasz, Achilleas S Frangakis, Evelin Schröck, Helmuth Steinmetz, Marina Jendrach, Udo Rüb, Ayşe Nazlı Başak, Wolfgang Oertel, Georg Auburger
Parkinson's disease (PD) is a frequent neurodegenerative process at old age. Accumulation and aggregation of the lipid-binding SNARE complex component alpha-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity are intensely investigated. In view of physiological SNCA roles in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation), to identify effects of SNCA gain-of-function as potential disease biomarkers...
January 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28107753/role-of-central-opioid-on-the-antinociceptive-effect-of-sulfated-polysaccharide-from-the-red-seaweed-solieria-filiformis-in-induced-temporomandibular-joint-pain
#9
Ianna Wivianne Fernandes Araújo, Hellíada Vasconcelos Chaves, José Mário Pachêco, Danielle Rocha Val, Lorena Vasconcelos Vieira, Rodrigo Santos, Raul Sousa Freitas, Renata Line Rivanor, Valdécio Silvano Monteiro, Juliana Trindade Clemente-Napimoga, Mirna Marques Bezerra, Norma Maria Barros Benevides
This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225μg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or μ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s...
January 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28107494/protective-roles-for-rgs2-in-a-mouse-model-of-house-dust-mite-induced-airway-inflammation
#10
Tresa George, Matthew Bell, Mainak Chakraborty, David P Siderovski, Mark A Giembycz, Robert Newton
The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2) reduces signalling from G-protein-coupled receptors (GPCRs) that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs) and long-acting β2-adrenoceptor agonists (LABAs) such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM)-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week) reduced lung function and induced granulocytic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28107431/characterization-of-a-broadly-reactive-anti-cd40-agonistic-monoclonal-antibody-for-potential-use-as-an-adjuvant
#11
Cameron Martin, Suryakant D Waghela, Shehnaz Lokhandwala, Andy Ambrus, Jocelyn Bray, Christina Vuong, Vanitha Vinodkumar, Paul J Dominowski, Sharath Rai, Duncan Mwangi, Dennis L Foss, Waithaka Mwangi
Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb), designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species...
2017: PloS One
https://www.readbyqxmd.com/read/28106772/neuroprotective-and-anti-apoptotic-effects-of-csp-1103-in-primary-cortical-neurons-exposed-to-oxygen-and-glucose-deprivation
#12
Vanessa Porrini, Ilenia Sarnico, Marina Benarese, Caterina Branca, Mariana Mota, Annamaria Lanzillotta, Arianna Bellucci, Edoardo Parrella, Lara Faggi, Pierfranco Spano, Bruno Pietro Imbimbo, Marina Pizzi
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28104813/structural-modeling-defines-transmembrane-residues-in-adam17-that-are-crucial-for-rhbdf2-adam17-dependent-proteolysis
#13
Xue Li, Thorsten Maretzky, Jose Manuel Perez-Aguilar, Sébastien Monette, Gisela Weskamp, Sylvain Le Gall, Bruce Beutler, Harel Weinstein, Carl P Blobel
A disintegrin and metalloproteinase 17 (ADAM17) controls the release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and is crucial for protecting the skin and intestinal barrier by proteolytic activation of Epidermal growth factor receptor (EGFR)-ligands. The seven-membrane spanning inactive Rhomboid2 (iRhom2; Rhbdf2) is required for ADAM17-dependent TNFα shedding and crosstalk with the EGFR, and a point mutation (sinecure, sin) in the first transmembrane domain (TMD) of Rhbdf2 (Rhbdf2(sin)) blocks TNFα shedding, yet little is known about the underlying mechanism...
January 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28104514/increased-foxp3-helios-regulatory-t-cells-and-decreased-acute-graft-versus-host-disease-after-allogeneic-bone-marrow-transplantation-in-patients-receiving-sirolimus-and-rgi-2001-an-activator-of-invariant-natural-killer-t-cells
#14
Yi-Bin Chen, Yvonne A Efebera, Laura Johnston, Edward D Ball, David Avigan, Lazaros J Lekakis, Carlos R Bachier, Paul Martin, Omar Duramad, Yasuyuki Ishii, Semi Han, Yu-Jin Jung, Dana Lee, Lori Kunkel, Robert S Negrin, Jack D Bui
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of GVHD after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells...
January 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28102754/enhancement-of-antibody-functions-through-fc-multiplications
#15
Qun Wang, Yan Chen, Mark Pelletier, Romana Cvitkovic, Jessica Bonnell, Chien-Ying Chang, Adem C Koksal, Ellen O'Connor, Xizhe Gao, Xiang-Qing Yu, Herren Wu, C Kendall Stover, William F Dall'Acqua, Xiaodong Xiao
Antibodies carry out a plethora of functions through their crystallizable fragment (Fc) regions, which can be naturally tuned by the adoption of several isotypes and post-translational modifications. Protein engineering enables further Fc function modulations through modifications of the interactions between the Fc and its functional partners, including FcγR, FcRn, complement complex, and additions of auxiliary functional units. Due to the many functions embedded within the confinement of an Fc, a suitable balance must be maintained for a therapeutic antibody to be effective and safe...
January 19, 2017: MAbs
https://www.readbyqxmd.com/read/28100503/chronic-kidney-disease-promotes-chronic-inflammation-in-visceral-white-adipose-tissue
#16
Dong Mei Xiang, Xiu Zhen Song, Zhan Mei Zhou, Yang Liu, Xiao Yan Dai, Xiang Lan Huang, Fan Fan Hou, Qiu Gen Zhou
White adipose tissue plays an important role in the development of metabolic disturbance which is a common feature in patients with chronic kidney disease (CKD). The effect of CKD on white adipose tissue remains poorly appreciated. Here we evaluated the inflammatory potential of visceral white adipose tissue in a rat model of CKD. The results showed production of pro-inflammatory cytokines and infiltration of macrophage in the tissue were significantly increased in CKD rats than sham rats. Moreover, the primary adipocytes and stromal vascular fraction under the condition of CKD could trigger the inflammatory response in each other...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#17
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28099883/beta2-adrenergic-signaling-affects-the-phenotype-of-human-cardiac-progenitor-cells-through-emt-modulation
#18
Francesca Pagano, Francesco Angelini, Camilla Siciliano, Julia Tasciotti, Giorgio Mangino, Elena De Falco, Roberto Carnevale, Sebastiano Sciarretta, Giacomo Frati, Isotta Chimenti
Human cardiac progenitor cells (CPCs) offer great promises to cardiac cell therapy for heart failure. Many in vivo studies have shown their therapeutic benefits, paving the way for clinical translation. The 3D model of cardiospheres (CSs) represents a unique niche-like in vitro microenvironment, which includes CPCs and supporting cells. CSs have been shown to form through a process mediated by epithelial-to-mesenchymal transition (EMT). β2-adrenergic signaling significantly affects stem/progenitor cells activation and mobilization in multiple tissues, and crosstalk between β2-adrenergic signaling and EMT processes has been reported...
January 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28099322/mitochondrial-dna-and-tlr9-signaling-is-not-involved-in-mechanical-ventilation-induced-inflammation
#19
Kim Timmermans, Matthijs Kox, Michiel Vaneker, Peter Pickkers, Gert Jan Scheffer
Exogenous administration of mitochondrial DNA (mtDNA) causes inflammatory lung injury in a toll-like receptor (TLR) 9-dependent manner. We investigated whether mechanical ventilation results in endogenous release of mtDNA and whether TLR9 plays a role in the pulmonary inflammatory response induced by mechanical ventilation.Wild-type and TLR9/ C57bl/6 mice were ventilated with low (8 mL/kg) and high (32 mL/kg) tidal volumes for 4 hours. Levels of nuclear DNA and mtDNA in bronchoalveolar lavage fluid, as well as pulmonary concentrations of keratinocyte-derived chemokine, interleukin-1β, and interleukin-6, were determined...
February 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28099120/the-clinical-significance-of-platelet-microparticle-associated-micrornas
#20
Patrick Provost
Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions...
January 18, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
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