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https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#1
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29334370/scaffolds-that-mimic-antigen-presenting-cells-enable-ex-vivo-expansion-of-primary-t-cells
#2
Alexander S Cheung, David K Y Zhang, Sandeep T Koshy, David J Mooney
Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads)...
January 15, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29334310/dendritic-polyglycerol-nanoparticles-show-charge-dependent-bio-distribution-in-early-human-placental-explants-and-reduce-hcg-secretion
#3
Herbert Juch, Liudmila Nikitina, Sabine Reimann, Martin Gauster, Gottfried Dohr, Barbara Obermayer-Pietsch, Denise Hoch, Karin Kornmueller, Rainer Haag
A thorough understanding of nanoparticle bio-distribution at the feto-maternal interface will be a prerequisite for their diagnostic or therapeutic application in women of childbearing age and for teratologic risk assessment. Therefore, the tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG-NPs) with first- trimester human placental explants were analyzed and compared to less sophisticated trophoblast-cell based models. First-trimester human placental explants, BeWo cells and primary trophoblast cells from human term placenta were exposed to fluorescence labeled, ∼5 nm dPG-NPs, with differently charged surfaces, at concentrations of 1 µM and 10 nM, for 6 and 24 h...
January 15, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29334147/uniform-lithium-nucleation-growth-induced-by-lightweight-nitrogen-doped-graphitic-carbon-foams-for-high-performance-lithium-metal-anodes
#4
Lin Liu, Ya-Xia Yin, Jin-Yi Li, Shu-Hua Wang, Yu-Guo Guo, Li-Jun Wan
The lithium metal anode has attracted soaring attention as an ideal battery anode. Unfortunately, nonuniform Li nucleation results in uncontrollable growth of dendritic Li, which incurs serious safety issues and poor electrochemical performance, hindering its practical applications. Herein, this study shows that uniform Li nucleation/growth can be induced by an ultralight 3D current collector consisting of in situ nitrogen-doped graphitic carbon foams (NGCFs) to realize suppressing dendritic Li growth at the nucleating stage...
January 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29334106/large-scale-preparation-of-a-3d-patchy-surface-with-dissimilar-dendritic-amphiphiles
#5
Yanyan Feng, Yujia Wan, Ming Jin, Decheng Wan
We show here the first example of the large-scale surface decoration of a macroscopic and porous monolith with dissimilar micropatches. Branched polyethylenimine (PEI) is alkylated with poly(propylene glycol) (PPG), leading to a reverse-micelle-like dendritic amphiphile of PEI@PPG. Peralkylation and partial quaternization of the residual amino groups of PEI@PPG produces a cationic dendritic amphiphile of PEI-N+@PPG. The two dendritic amphiphiles jointly stabilize a water-in-oil high-internal-phase emulsion to prepare open-cellular monoliths of macroscopic size, with the monolith pore surface dictated by the cationic and neutral dendritic amphiphiles...
January 15, 2018: Soft Matter
https://www.readbyqxmd.com/read/29331876/app-go-protein-g%C3%AE-%C3%AE-complex-signaling-mediates-a%C3%AE-degeneration-and-cognitive-impairment-in-alzheimer-s-disease-models
#6
Elena Anahi Bignante, Nicolás Eric Ponce, Florencia Heredia, Juliana Musso, María C Krawczyk, Julieta Millán, Gustavo F Pigino, Nibaldo C Inestrosa, Mariano M Boccia, Alfredo Lorenzo
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331804/toll-like-receptor-9-antagonist-suppresses-humoral-immunity-in-experimental-autoimmune-myasthenia-gravis
#7
Peng Zhang, Chun-Lin Yang, Ru-Tao Liu, Heng Li, Min Zhang, Na Zhang, Long-Tao Yue, Cong-Cong Wang, Ying-Chun Dou, Rui-Sheng Duan
Recent studies have demonstrated the important role of toll-like receptor 9 (TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG) has not been fully established. We show herein that blocking TLR9 signalling via the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of experimental autoimmune myasthenia gravis (EAMG). With the downregulation of dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh) and germinal centre (GC) B cells, leading to decreased antibody production...
January 11, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29331768/the-cholinergic-anti-inflammatory-pathway-an-innovative-treatment-strategy-for-respiratory-diseases-and-their-comorbidities
#8
REVIEW
Mitsuhiro Yamada, Masakazu Ichinose
Over the past few decades, it has been clarified that the nervous system and immune system have overlapping distributions and their interactions are critical in the regulation of immunological and inflammatory responses. The cholinergic anti-inflammatory pathway, including the parasympathetic nerve systems and humoral factors orchestrate the immune responses to protect the body during infection and tissue injury. Recent investigations have attempted to clarify how the parasympathetic nerve systems attenuate the systemic inflammatory responses and identified the α7 nicotinic acetylcholine receptor (α7nAChR) as a crucial target for attenuating the release of inflammatory cytokines from inflammatory cells including macrophages and dendritic cells...
January 11, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#9
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#10
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29330750/immunologic-and-gene-expression-profiles-of-spontaneous-canine-oligodendrogliomas
#11
Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A Miller, Yunlong Liu, R Timothy Bentley, Mahua Dey
Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29330744/c-fos-downregulation-positively-regulates-epha5-expression-in-a-congenital-hypothyroidism-rat-model
#12
Honghua Song, Yuqin Zheng, Fuying Cai, Yanyan Ma, Jingyue Yang, Youjia Wu
The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites...
January 12, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29330324/betaine-ameliorates-experimental-autoimmune-encephalomyelitis-by-inhibiting-dendritic-cell-derived-il-6-production-and-th17-differentiation
#13
Cuixia Yang, Weiming Lai, Jinfeng Zhou, Xinyuan Zheng, Yingying Cai, Wanjie Yang, Sirong Xie, Yuan Gao, Changsheng Du
IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)-derived cytokines play pivotal roles in promoting the differentiation of naive CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules blocking the key cytokines produced by DCs will be beneficial in MS. In this article, we report that betaine treatment ameliorates MS pathogenesis by inhibiting DC-derived IL-6 production and Th17 differentiation...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29330321/osteopontin-promotes-protective-antigenic-tolerance-against-experimental-allergic-airway-disease
#14
Themis Alissafi, Evangelia Kourepini, Davina C M Simoes, Nikolaos Paschalidis, Maria Aggelakopoulou, Tim Sparwasser, Louis Boon, Hamida Hammad, Bart N Lambrecht, Vily Panoutsakopoulou
In the context of inflammation, osteopontin (Opn) is known to promote effector responses, facilitating a proinflammatory environment; however, its role during antigenic tolerance induction is unknown. Using a mouse model of asthma, we investigated the role of Opn during antigenic tolerance induction and its effects on associated regulatory cellular populations prior to disease initiation. Our experiments demonstrate that Opn drives protective antigenic tolerance by inducing accumulation of IFN-β-producing plasmacytoid dendritic cells, as well as regulatory T cells, in mediastinal lymph nodes...
January 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29330091/cdc42ep4-a-perisynaptic-scaffold-protein-in-bergmann-glia-is-required-for-glutamatergic-tripartite-synapse-configuration
#15
Natsumi Ageta-Ishihara, Kohtarou Konno, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Makoto Kinoshita
Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB...
January 9, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29329908/anatomical-evidence-for-lateral-hypothalamic-innervation-of-the-pontine-a7-catecholamine-cell-group-in-rat
#16
Janean E Holden, Monica A Wagner, Brady L Reeves
Substantial behavioral evidence exists to support the idea that the lateral hypothalamus (LH) makes axonal connection with spinally-projecting noradrenergic neurons of the A7 catecholamine cell group in the pons. Through this putative projection, the LH modulates nociception via α1- and α2-adrenoceptors in the dorsal horn. We used double-label immunocytochemistry to demonstrate that axons from the LH labeled with the anterograde tracer biotinylated dextran amine (BDA) appose tyrosine hydroxylase-immunoreactive (TH-ir) neuron profiles in the A7 area...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29329906/development-of-a-quick-bioassay-for-the-evaluation-of-transmission-properties-of-acquired-prion-diseases
#17
Yoshiko Munesue, Taishi Shimazaki, Zechen Qi, Norikazu Isoda, Hirofumi Sawa, Keisuke Aoshima, Takashi Kimura, Shirou Mohri, Tetsuyuki Kitamoto, Atsushi Kobayashi
Evaluation of transmission properties is important for the differential diagnosis of a subgroup of acquired Creutzfeldt-Jakob disease (CJD) with methionine homozygosity at polymorphic codon 129 of the PRNP gene, an intermediate type abnormal prion protein (PrP), and kuru plaques, denoted as acquired CJD-MMiK. The present study aimed to develop a quick evaluation system of the transmission properties of acquired CJD-MMiK. In the PrP-humanized mice intraperitoneally inoculated with brain homogenates from an acquired CJD-MMiK patient, accumulation of abnormal PrP was observed in follicular dendritic cells of the spleen at 75 days post-inoculation...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29329879/mir-134-modulates-chronic-stress-induced-structural-plasticity-and-depression-like-behaviors-via-downregulation-of-limk1-cofilin-signaling-in-rats
#18
Cuiqin Fan, Xiuzhi Zhu, Qiqi Song, Peng Wang, Zhuxi Liu, Shu Yan Yu
Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC)...
January 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#19
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29328028/-skin-pathology-in-diabetes-mellitus-clinical-and-pathophysiological-correlations-review
#20
K Kochet, I Lytus, I Svistunov, O Sulaieva
Skin pathology is registered in vast majority of patients with diabetes mellitus (DM). Despite the abundance of publications on dermatological problems in DM, there is still a number of gaps to be discussed in terms of pathophysiological mechanisms. The goal of this review was to assess the mechanisms of development of different skin pathologies under DM. One of the key pathogenic mechanisms of skin lesions in diabetes is hyperglycemia and the effects of the advanced glycation end products, inducing oxidative stress, endothelial dysfunction and inflammation; that in its turn can accelerate the mechanisms of skin aging, the development of diabetic dermopathy and scleredema diabeticorum...
December 2017: Georgian Medical News
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