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https://www.readbyqxmd.com/read/28346227/reducing-expression-of-synapse-restricting-protein-ephexin5-ameliorates-alzheimer-s-like-impairment-in-mice
#1
Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
Accumulation of amyloid-β (Aβ) protein may cause synapse degeneration and cognitive impairment in Alzheimer's disease (AD) by reactivating expression of the developmental synapse repressor protein Ephexin5 (also known as ARHGEF15). Here, we have reported that Aβ is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein (hAPP mice), a model for familial AD that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345671/spatiotemporal-expression-of-osteopontin-in-the-striatum-of-rats-subjected-to-the-mitochondrial-toxin-3-nitropropionic-acid-correlates-with-microcalcification
#2
Tae-Ryong Riew, Hong Lim Kim, Xuyan Jin, Jeong-Heon Choi, Yoo-Jin Shin, Ji Soo Kim, Mun-Yong Lee
Our aim was to elucidate whether osteopontin (OPN) is involved in the onset of mineralisation and progression of extracellular calcification in striatal lesions due to mitochondrial toxin 3-nitropropionic acid exposure. OPN expression had two different patterns when observed using light microscopy. It was either localised to the Golgi complex in brain macrophages or had a small granular pattern scattered in the affected striatum. OPN labelling tended to increase in number and size over a 2-week period following the lesion...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345586/new-insights-into-mononuclear-phagocyte-biology-from-the-visual-system
#3
REVIEW
Nancy J Reyes, Emily G O'Koren, Daniel R Saban
Major advances in mononuclear phagocyte biology have been made but key questions pertinent to their roles in health and disease remain, including in the visual system. One problem concerns how dendritic cells can trigger immune responses from certain tightly regulated immune- privileged sites of the eye. Another, albeit separate, problem involves whether there are functional specializations for microglia versus monocytes in retinal neurodegeneration. In this Review, we examine novel insights in eye immune privilege and, separately, we discuss recent inroads concerning retinal degeneration...
March 27, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28345021/oncolytic-group-b-adenovirus-enadenotucirev-mediates-non-apoptotic-cell-death-with-membrane-disruption-and-release-of-inflammatory-mediators
#4
Arthur Dyer, Ying Di, Hugo Calderon, Sam Illingworth, Gray Kueberuwa, Alison Tedcastle, Phil Jakeman, Suet Lin Chia, Alice Brown, Michael A Silva, David Barlow, John Beadle, Terry Hermiston, David J P Ferguson, Brian Champion, Kerry D Fisher, Leonard W Seymour
Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent. The EnAd death pathway does not involve p53, is predominantly caspase independent, and appears to involve a rapid fall in cellular ATP...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344989/efficient-presentation-of-multiple-endogenous-epitopes-to-both-cd4-and-cd8-diabetogenic-t-cells-for-tolerance
#5
Shamael R Dastagir, Jorge Postigo-Fernandez, Chunliang Xu, James H Stoeckle, Rebuma Firdessa-Fite, Rémi J Creusot
Antigen-specific immunotherapy of type 1 diabetes, typically via delivery of a single native β cell antigen, has had little clinical benefit to date. With increasing evidence that diabetogenic T cells react against multiple β cell antigens, including previously unappreciated neo-antigens that can be emulated by mimotopes, a shift from protein- to epitope-based therapy is warranted. To this end, we aimed to achieve efficient co-presentation of multiple major epitopes targeting both CD4(+) and CD8(+) diabetogenic T cells...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344885/pappalysin-1-t-cell-receptor-transgenic-allo-restricted-t-cells-kill-ewing-sarcoma-in-vitro-and-in-vivo
#6
Andreas Kirschner, Melanie Thiede, Thomas G P Grünewald, Rebeca Alba Rubio, Günther H S Richter, Thomas Kirchner, Dirk H Busch, Stefan Burdach, Uwe Thiel
Pregnancy-associated plasma protein-A (PAPPA), also known as pappalysin, is a member of the insulin-like growth factor (IGF) family. PAPPA acts as a protease, cleaving IGF inhibitors, i.e., IGF binding proteins (IGFBPs), thereby setting free IGFs. The insulin/IGF-axis is involved in cancer in general and in Ewing sarcoma (ES) in particular. ES is a highly malignant bone tumor characterized by early metastatic spread. PAPPA is associated with various cancers. It is overexpressed and required for proliferation in ES...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344872/intravenously-usable-fully-serotype-3-oncolytic-adenovirus-coding-for-cd40l-as-an-enabler-of-dendritic-cell-therapy
#7
Sadia Zafar, Suvi Parviainen, Mikko Siurala, Otto Hemminki, Riikka Havunen, Siri Tähtinen, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Akseli Hemminki
Vaccination with dendritic cells (DCs), the most potent professional antigen-presenting cells in the body, is a promising approach in cancer immunotherapy. However, tumors induce immunosuppression in their microenvironment that suppresses and impairs the function of DCs. Therefore, human clinical trials with DC therapy have often been disappointing. To improve the therapeutic efficacy and to overcome the major obstacles of DC therapy, we generated a novel adenovirus, Ad3-hTERT-CMV-hCD40L, which is fully serotype 3 and expresses hCD40L for induction of antitumor immune response...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344860/il-32-induces-indoleamine-2-3-dioxygenase-cd1c-dendritic-cells-and-indoleamine-2-3-dioxygenase-cd163-macrophages-relevance-to-mycosis-fungoides-progression
#8
Hanako Ohmatsu, Daniel Humme, Juana Gonzalez, Nicholas Gulati, Markus Möbs, Wolfram Sterry, James G Krueger
Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c(+) myeloid dendritic cells (mDC) and/or CD163(+) macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344660/predictive-biomarkers-and-effectiveness-of-muc1-targeted-dendritic-cell-based-vaccine-in-patients-with-refractory-non-small-cell-lung-cancer
#9
Koji Teramoto, Yoshitomo Ozaki, Jun Hanaoka, Satoru Sawai, Noriaki Tezuka, Shozo Fujino, Yataro Daigo, Keiichi Kontani
BACKGROUND: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. METHODS: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28344548/gsk-3%C3%AE-overexpression-alters-the-dendritic-spines-of-developmentally-generated-granule-neurons-in-the-mouse-hippocampal-dentate-gyrus
#10
Noemí Pallas-Bazarra, Asta Kastanauskaite, Jesús Avila, Javier DeFelipe, María Llorens-Martín
The dentate gyrus (DG) plays a crucial role in hippocampal-related memory. The most abundant cellular type in the DG, namely granule neurons, are developmentally generated around postnatal day P6 in mice. Moreover, a unique feature of the DG is the occurrence of adult hippocampal neurogenesis, a process that gives rise to newborn granule neurons throughout life. Adult-born and developmentally generated granule neurons share some maturational aspects but differ in others, such as in their positioning within the granule cell layer...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28344338/monitoring-of-dynamic-changes-in-keyhole-limpet-hemocyanin-klh-specific-b-cells-in-klh-vaccinated-cancer-patients
#11
Florian Wimmers, Nienke de Haas, Anja Scholzen, Gerty Schreibelt, Elles Simonetti, Marc J Eleveld, Huberdina M L M Brouwers, Marjo Beldhuis-Valkis, Irma Joosten, Marien I de Jonge, Winald R Gerritsen, I Jolanda M de Vries, Dimitri A Diavatopoulos, Joannes F M Jacobs
Keyhole limpet hemocyanin (KLH) is used as an immunogenic neo-antigen for various clinical applications and during vaccine development. For advanced monitoring of KLH-based interventions, we developed a flow cytometry-based assay for the ex vivo detection, phenotyping and isolation of KLH-specific B cells. As proof-of-principle, we analyzed 10 melanoma patients exposed to KLH during anti-cancer dendritic cell vaccination. Our assay demonstrated sensitive and specific detection of KLH-specific B cells in peripheral blood and KLH-specific B cell frequencies strongly correlated with anti-KLH serum antibody titers...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344318/recurrent-myb-rearrangement-in-blastic-plasmacytoid-dendritic-cell-neoplasm
#12
K Suzuki, Y Suzuki, A Hama, H Muramatsu, M Nakatochi, M Gunji, D Ichikawa, M Hamada, R Taniguchi, S Kataoka, N Murakami, D Kojima, Y Sekiya, E Nishikawa, N Kawashima, A Narita, N Nishio, Y Nakazawa, H Iwafuchi, K-I Watanabe, Y Takahashi, M Ito, S Kojima, S Kato, Y Okuno
Leukemia accepted article preview online, 27 March 2017. doi:10.1038/leu.2017.101.
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28344062/il-21-may-promote-granzyme-b-dependent-nk-plasmacytoid-dendritic-cell-functional-interaction-in-cutaneous-lupus-erythematosus
#13
Valentina Salvi, William Vermi, Andrea Cavani, Silvia Lonardi, Teresa Carbone, Fabio Facchetti, Daniela Bosisio, Silvano Sozzani
Autoimmune skin lesions are characterized by a complex cytokine milieu and by the accumulation of plasmacytoid dendritic cells (pDCs). Granzyme B (GrB) transcript is abundant in activated pDCs, though its mechanisms of regulation and biological role are largely unknown. Here we report that IL-21 was the only Th1/Th17 cytokine able to induce the expression and secretion of GrB by pDCs and that this action was counteracted by the autocrine production of type I interferons (IFNs). In lupus erythematosus (LE) skin lesions, the percentage of GrB(+) pDCs directly correlated with the IL-21/MxA ratio, indicating that the interplay between these two cytokines finely tune the levels of pDC-dependent GrB also in vivo...
March 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28344018/enhanced-topical-penetration-system-exposure-and-anti-psoriasis-activity-of-two-particle-sized-curcumin-loaded-plga-nanoparticles-in-hydrogel
#14
Lin Sun, Zeyu Liu, Lun Wang, Dongmei Cun, Henry H Y Tong, Ru Yan, Xin Chen, Ruibing Wang, Ying Zheng
Psoriasis is an immune-mediated skin disorder, which is triggered by the aberrant activation of dendritic cells in skin. This activation is followed by the complex interaction between the immune cells in the skin and keratinocyte in the epidermis. To improve the conditions of poor aqueous solubility and chemical stability, overcome skin barriers, and enhance in-vivo anti-psoriatic activity, curcumin (Cur) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were fabricated and administered by topical route to treat Imiquimod (IMQ)-induced psoriasis-like mouse model...
March 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28343701/toll-like-receptor-8-agonist-nanoparticles-mimic-immunomodulating-effects-of-the-live-bcg-vaccine-and-enhance-neonatal-innate-and-adaptive-immune-responses
#15
David J Dowling, Evan A Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K Bonner, Sachiko Hirosue, Melody A Swartz, Jeffrey A Hubbell, Ofer Levy
BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form...
March 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28343296/ibuprofen-protects-from-cypermethrin-induced-changes-in-the-striatal-dendritic-length-and-spine-density
#16
Pratibha Tripathi, Ashish Singh, Lakshmi Bala, Devendra Kumar Patel, Mahendra Pratap Singh
Microgliosis and inflammation are major wrongdoers in cypermethrin-induced Parkinsonism along with oxidative stress, mitochondrial dysfunction and α-synuclein aggregation. Dopamine depletion could alter dendritic morphology, length and spine number in the striatum. Present study investigated the effect of ibuprofen on the dendritic morphology, length and spine density in cypermethrin PD model. Male pups were treated intraperitoneally with cypermethrin during postnatal days followed by adulthood to induce Parkinsonism using standard procedure along with controls...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28343248/uncovering-specific-changes-in-network-wiring-underlying-the-primate-cerebrotype
#17
Salah Hamodeh, Ayse Bozkurt, Haian Mao, Fahad Sultan
Regular scaling of brain networks during evolution has been proposed to be the major process leading to enlarged brains. Alternative views, however, suggest that deviations from regular scaling were crucial to the evolution of the primate brain and the emergence of different cerebrotypes. Here, we examined the scaling within the major link between the cerebellum and the cerebral cortex by studying the deep cerebellar nuclei (DCN). We compared the major axonal and dendritic wiring in the DCN of rodents and monkeys in search of regular scaling...
March 25, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28343120/nanoemulgel-using-a-bicephalous-heterolipid-as-a-novel-approach-to-enhance-transdermal-permeation-of-tenofovir
#18
Sanjeev Rambharose, Rahul S Kalhapure, Thirumala Govender
Improvements in permeation enhancement strategies, such as nanoemulsions (NEs) and nanoemulgels (NEGs), have led to a renewed interest in transdermal drug delivery (TDD). This study aimed to investigate the potential of LLA1E, a novel dendritic permeation enhancer, as an oily phase in the development of a NEG for the TDD of tenofovir (TNF). TNF loaded NEs (TNEs) were prepared and analysed for mean globule diameter (MGD), polydispersity index (PDI), zeta potential (ZP) and morphology. NEGs of the TNEs (TNEGs) were prepared and evaluated for ex vivo transdermal permeation efficacy...
March 19, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28342978/a-new-benzenediamine-derivative-modulates-toll-like-receptors-induced-myeloid-dendritic-cells-activation-and-ameliorates-lupus-like-syndrome-in-mrllpr-lpr-mice
#19
Sheng Gao, Yongsheng Gong, Jianjian Ji, Linbo Yuan, Liping Han, Yimin Guo, Xiaofang Fan, Yayi Hou, Chunyan Hua
Modulators of the over-activation of myeloid dendritic cells (mDCs) by Toll-like receptors (TLRs) have an advantage in the treatment of systemic lupus erythematosus (SLE). This study was designed to evaluate the effects of FC-99, a novel benzenediamine derivative, on TLR-induced activation of mDCs, and to assess the efficacy of FC-99 in a murine model of SLE. In vitro, FC-99 inhibited the phenotypic (CD40 and MHC-II) and functional activation (IL-12 and CXCL10) of mDCs induced by TLR ligands. In vivo, MRLlpr/lpr mice displayed renal diseases associated with increased levels of proteinuria and immunoglobulin, which were ameliorated by FC-99...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#20
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
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