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https://www.readbyqxmd.com/read/29245178/transcriptional-regulation-of-cd4-t-cell-differentiation-in-experimentally-induced-arthritis-and-rheumatoid-arthritis
#1
REVIEW
Yuya Kondo, Masahiro Yokosawa, Shunta Kaneko, Kotona Furuyama, Seiji Segawa, Hiroto Tsuboi, Isao Matsumoto, Takayuki Sumida
Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by infiltration of the joint synovium by activated inflammatory cells. CD4+ T cells form a large proportion of the inflammatory cells invading the synovial tissue, and are involved in the RA pathological process. In general, CD4+ T cells differentiate into various T helper (Th) cell subsets and acquire the functional characterization to respond to specific pathogens, and also mediated some autoimmune disorders such as RA. Because the differentiation of Th cell subsets is determined by the expression of specific transcription factors in response to cytokine environment, these transcription factors is considered to have a role in pathology of RA...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29244957/hypercementosis-associated-with-enpp1-mutations-and-gaci
#2
V Thumbigere-Math, A Alqadi, N I Chalmers, M B Chavez, E Y Chu, M T Collins, C R Ferreira, K FitzGerald, R I Gafni, W A Gahl, K S Hsu, M S Ramnitz, M J Somerman, S G Ziegler, B L Foster
Mineralization of bones and teeth is tightly regulated by levels of extracellular inorganic phosphate (Pi) and pyrophosphate (PPi). Three regulators that control pericellular concentrations of Pi and PPi include tissue-nonspecific alkaline phosphatase (TNAP), progressive ankylosis protein (ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Inactivation of these factors results in mineralization disorders affecting teeth and their supporting structures. This study for the first time analyzed the effect of decreased PPi on dental development in individuals with generalized arterial calcification of infancy (GACI) due to loss-of-function mutations in the ENPP1 gene...
December 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29244882/%C3%AE-ii-spectrin-in-t-cells-is-involved-in-the-regulation-of-cell-cell-contact-leading-to-immunological-synapse-formation
#3
Justyna M Meissner, Aleksander F Sikorski, Tomasz Nawara, Jakub Grzesiak, Krzysztof Marycz, Dżamila M Bogusławska, Izabela Michalczyk, Marie-Christine Lecomte, Beata Machnicka
T-lymphocyte activation after antigen presentation to the T-Cell Receptor (TCR) is a critical step in the development of proper immune responses to infection and inflammation. This dynamic process involves reorganization of the actin cytoskeleton and signaling molecules at the cell membrane, leading to the formation of the Immunological Synapse (IS). The mechanisms regulating the formation of the IS are not completely understood. Nonerythroid spectrin is a membrane skeletal protein involved in the regulation of many cellular processes, including cell adhesion, signaling and actin cytoskeleton remodeling...
2017: PloS One
https://www.readbyqxmd.com/read/29244745/immunotherapeutic-potential-of-oncolytic-h-1-parvovirus-hints-of-glioblastoma-microenvironment-conversion-towards-immunogenicity
#4
Assia L Angelova, Milena Barf, Karsten Geletneky, Andreas Unterberg, Jean Rommelaere
Glioblastoma, one of the most aggressive primary brain tumors, is characterized by highly immunosuppressive microenvironment. This contributes to glioblastoma resistance to standard treatment modalities and allows tumor growth and recurrence. Several immune-targeted approaches have been recently developed and are currently under preclinical and clinical investigation. Oncolytic viruses, including the autonomous protoparvovirus H-1 (H-1PV), show great promise as novel immunotherapeutic tools. In a first phase I/IIa clinical trial (ParvOryx01), H-1PV was safe and well tolerated when locally or systemically administered to recurrent glioblastoma patients...
December 15, 2017: Viruses
https://www.readbyqxmd.com/read/29244152/regulation-of-t-cell-proliferation-with-drug-responsive-microrna-switches
#5
Remus S Wong, Yvonne Y Chen, Christina D Smolke
As molecular and cellular therapies advance in the clinic, the role of genetic regulation is becoming increasingly important for controlling therapeutic potency and safety. The emerging field of mammalian synthetic biology provides promising tools for the construction of regulatory platforms that can intervene with endogenous pathways and control cell behavior. Recent work has highlighted the development of synthetic biological systems that integrate sensing of molecular signals to regulated therapeutic function in various disease settings...
December 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29243498/-cart-intensification-by-the-hiv-1-tat-b-clade-vaccine-progress-to-phase-iii-efficacy-studies
#6
Aurelio Cafaro, Cecilia Sgadari, Orietta Picconi, Antonella Tripiciano, Sonia Moretti, Vittorio Francavilla, Maria Rosaria Pavone Cossut, Stefano Buttò, Giovanni Cozzone, Fabrizio Ensoli, Paolo Monini, Barbara Ensoli
In spite of its success at suppressing HIV replication, combination antiretroviral therapy (cART) only partially reduces immune dysregulation and loss of immune functions. These cART-unmet needs appear to be due to persistent virus replication and cell-to-cell transmission in reservoirs, and are causes of increased patients' morbidity and mortality. Up to now, therapeutic interventions aimed at cART-intensification by attacking the virus reservoir have failed. Areas covered: We briefly review the rationale and clinical development of Tat therapeutic vaccine in cART-treated subjects in Italy and South Africa (SA)...
December 15, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29243219/pd-1-blockade-enhances-the-anti-tumor-efficacy-of-gm-csf-surface-modified-bladder-cancer-stem-cells-vaccine
#7
Xiaojun Shi, Xinji Zhang, Jinlong Li, Lijun Mo, Hongfan Zhao, Yongtong Zhu, Zhiming Hu, Jimin Gao, Wanlong Tan
Eliminating cancer stem cells (CSCs) is a key issue in eradicating tumor. The streptavidin-granulocyte -macrophage colony stimulating factor (SA-GM-CSF) surface-modified bladder cancer stem cells vaccine previously developed using our protein-anchor technology could effectively induce specific immune response for eliminating CSCs. However, program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling in tumor microenvironment results in tumor adaptive immune resistance. Although the CSCs vaccine could increase the number of CD8+ T-cells, a part of these CD8+ T-cells expressed PD-1...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29243131/analysis-of-variability-of-urinary-excreted-jc-virus-strains-in-patients-infected-with-hiv-and-healthy-donors
#8
Danijela Karalic, Ivana Lazarevic, Ana Banko, Maja Cupic, Djordje Jevtovic, Tanja Jovanovic
In immunocompromised individuals, especially in patients with T cell immunodeficiency, reactivation of JCPyV can cause serious life-threatening diseases. Nowadays, HIV infection is one of the most important factor for reactivation of JCPyV and the development of of the progressive multifocal leukoencephalopathy (PML). Mutations in the outer loops of the VP1 region can lead to the selection of the viral variants with changed tropism and increased pathological potential. The aims of this study were to determine sequence variation and amino acid changes within VP1 loops and the structure of non-coding control region (NCCR) of urinary excreted JCPyV isolates among HIV-infected patients and healthy donors...
December 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29242771/sentinels-at-the-frontline-the-role-of-intraepithelial-lymphocytes-in-inflammatory-bowel-disease
#9
Madeleine D Hu, Karen L Edelblum
Purpose of review: Intestinal mucosal immunity is tightly regulated to ensure effective host defense against invasive microorganisms while limiting the potential for aberrant damage. In inflammatory bowel disease (IBD), an imbalance between effector and regulatory T cell populations results in an uncontrolled inflammatory response to commensal bacteria. Intraepithelial lymphocytes (IEL) are perfectly positioned within the intestinal epithelium to provide the first line of mucosal defense against luminal microbes or rapidly respond to epithelial injury...
December 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/29242639/development-of-an-adenovirus-vector-vaccine-platform-for-targeting-dendritic-cells
#10
Piyush K Sharma, Igor P Dmitriev, Elena A Kashentseva, Geert Raes, Lijin Li, Samuel W Kim, Zhi-Hong Lu, Jeffrey M Arbeit, Timothy P Fleming, Sergey A Kaliberov, S Peter Goedegebuure, David T Curiel, William E Gillanders
Adenoviral (Ad) vector vaccines represent one of the most promising modern vaccine platforms, and Ad vector vaccines are currently being investigated in human clinical trials for infectious disease and cancer. Our studies have shown that specific targeting of adenovirus to dendritic cells dramatically enhanced vaccine efficacy. However, this was achieved using a molecular adapter, thereby necessitating a two component vector approach. To address the mandates of clinical translation of our strategy, we here sought to accomplish the goal of DC targeting with a single-component adenovirus vector approach...
December 15, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29242405/digitalis-like-compounds-restore-hnis-expression-and-iodide-uptake-capacity-in-anaplastic-thyroid-cancer
#11
Marika H Tesselaar, Thomas Crezee, Imke Schuurmans, Danny Gerrits, James Nagarajah, Otto C Boerman, Ilse van Engen-van Grunsven, Johannes W A Smit, Romana T Netea-Maier, Theo S Plantinga
Purpose: Anaplastic thyroid cancer (ATC) is a rare malignancy that accounts for 1-2% of all thyroid cancers. ATC is one of the most aggressive human cancers, with rapid growth, tumor invasion and development of distant metastases. The median survival is only 5 months and the 1-year survival is less than 20%. Moreover, as a result of severe dedifferentiation including the loss of human sodium iodide symporter (hNIS) expression, radioactive iodide (RAI) therapy is ineffective. Recently, we have demonstrated beneficial effects of autophagy activating digitalis-like compounds (DLCs) on redifferentiation and concomitant restoration of iodide uptake in RAI-refractory papillary and follicular thyroid cancer cell lines...
December 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29242308/chemokine-c-c-motif-receptor-like-2-is-not-essential-for-lung-injury-lung-inflammation-or-airway-hyperresponsiveness-induced-by-acute-exposure-to-ozone
#12
Farhan Malik, Kevin R Cromar, Constance L Atkins, Roger E Price, William T Jackson, Saad R Siddiqui, Chantal Y Spencer, Nicholas C Mitchell, Ikram U Haque, Richard A Johnston
Inhalation of ozone (O3), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O3 Furthermore, each of these aforementioned cells express chemokine (C-C motif) receptor-like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O3-induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O3, we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O3 To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl-β-methylcholine chloride (respiratory system resistance) in wild-type and mice genetically deficient in Ccrl2 (Ccrl2-deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O3 In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29242302/a-distinct-subtype-of-epstein-barr-virus-positive-t-nk-cell-lymphoproliferative-disorder-adult-patients-with-chronic-active-epstein-barr-virus-infection-like-features
#13
Keisuke Kawamoto, Hiroaki Miyoshi, Takaharu Suzuki, Yasuji Kozai, Koji Kato, Masaharu Miyahara, Toshiaki Yujiri, Naoki Oishi, Ilseung Choi, Katsumichi Fujimaki, Tsuyoshi Muta, Masaaki Kume, Sayaka Moriguchi, Shinobu Tamura, Takeharu Kato, Hiroyuki Tagawa, Junya Makiyama, Yuji Kanisawa, Yuya Sasaki, Daisuke Kurita, Kyohei Yamada, Joji Shimono, Hirohito Sone, Jun Takizawa, Masao Seto, Hiroshi Kimura, Koichi Ohshima
The characteristics of adult patients with chronic active Epstein-Barr virus infection (adult-onset CAEBV) are poorly recognized, hindering early diagnosis and an improved prognosis. Adult-onset CAEBV (n = 54) diagnosed between 2005 and 2015 were conducted. Adult-onset was defined as an estimated age of onset ≥15 years. To characterize the clinical features of adult-onset CAEBV, we compared them to those of pediatric-onset (estimated age of onset <15 years) patients (n = 75). We compared the prognosis of adult-onset CAEBV with that for patients with nasal-type (n = 37) and non-nasal-type (n = 45) extranodal NK/T-cell lymphoma (ENKTL)...
December 14, 2017: Haematologica
https://www.readbyqxmd.com/read/29242279/molecular-biomarkers-of-primary-and-acquired-resistance-to-t-cell-mediated-immunotherapy-in-cancer-landscape-clinical-implications-and-future-directions
#14
REVIEW
Young Kwang Chae, Michael S Oh, Francis J Giles
The emergence of immunotherapy has revolutionized cancer treatment in recent years. Inhibitors of immune checkpoints, including antibodies against cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, and programmed death ligand 1, have demonstrated notable efficacy in certain advanced cancers. Unfortunately, many patients do not benefit from these therapies and either exhibit primary resistance to treatment or develop acquired mechanisms of resistance after initially responding to therapy...
December 14, 2017: Oncologist
https://www.readbyqxmd.com/read/29242243/an-infrared-dye-conjugated-virus-like-particle-for-the-treatment-of-primary-uveal-melanoma
#15
Rhonda C Kines, Isabella Varsavsky, Sanghamitra Choudhary, Debaditya Bhattacharya, Sean Spring, Roger J McLaughlin, Shin J Kang, Hans E Grossniklaus, Demitrios G Vavvas, Stephen Monks, John R MacDougall, Elisabet de Los Pinos, John T Schiller
The work outlined herein describes AU-011, a novel recombinant papillomavirus-like particle (VLP) drug conjugate and its initial evaluation as a potential treatment for primary uveal melanoma. The VLP is conjugated with a phthalocyanine photosensitizer, IRDye 700DX, that exerts its cytotoxic effect through photo-activation with a near-infrared laser. We assessed the anti-cancer properties of AU-011 in vitro utilizing a panel of human cancer cell lines and in vivo using murine subcutaneous and rabbit orthotopic xenograft models of uveal melanoma...
December 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29242169/c60-fullerenes-disrupt-cellular-signalling-leading-to-trpc4-and-trpc6-channels-opening-by-the-activation-of-muscarinic-receptors-and-g-proteins-in-small-intestinal-smooth-muscles
#16
Dariia O Dryn, Mariia I Melnyk, Lina T Al Kury, Yuriy I Prylutskyy, Uwe Ritter, Alexander V Zholos
The effect of water-soluble pristine C60 fullerene nanoparticles (C60NPs) on receptor-operated cation channels formed by TRPC4/C6 proteins in ileal smooth muscle cells was investigated for the first time. Activation of these channels subsequent to acetylcholine binding to the expressed in these cells M2 and M3 muscarinic receptors represents the key event in the parasympathetic control of gastrointestinal smooth muscle motility and cholinergic excitation-contraction coupling. Experiments were performed on single collagenase-dispersed mouse ileal myocytes using patch-clamp techniques with symmetrical 125mM Cs+ solutions and [Ca2+]i 'clamped' at 100nM in order to isolate the muscarinic cation current (mICAT)...
December 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29242008/immune-responses-to-peptides-containing-homocitrulline-or-citrulline-in-the-dr4-transgenic-mouse-model-of-rheumatoid-arthritis
#17
Patrick Lac, Sheri Saunders, Elena Tutunea-Fatan, Lillian Barra, David A Bell, Ewa Cairns
Antibodies to proteins/peptides containing citrulline are hallmarks of Rheumatoid Arthritis (RA). These antibodies are strongly associated with the expression of the Shared Epitope (SE). RA patients also generate antibodies to homocitrulline-containing proteins/peptides (also referred to as anti-carbamylated protein antibodies (Anti-CarP)). This study was undertaken to investigate the relationship between homocitrulline and citrulline immune responses using an established mouse model of RA: DR4-transgenic (DR4tg) mice that express the human SE...
December 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29241982/monocyte-profile-in-peripheral-blood-of-gestational-diabetes-mellitus-patients
#18
Ana G S Angelo, Carla T C Neves, Thalita F Lobo, Ramon V C Godoy, Érika Ono, Rosiane Mattar, Silvia Daher
OBJECTIVE: Gestational diabetes Mellitus has been considered an inflammatory disease involving different cells and mediators in its development. The role of innate immune cells in GDM physiopathology remains unclear, therefore this study was conducted to assess monocyte profile in GDM patients. DESIGN: This was a case-control study including 20 glucose-tolerant pregnant women (controls) and 18 GDM patients. METHODS: Flow cytometry was used to assess peripheral blood monocytes subsets (classical, intermediate, non-classical), the expression of TLR4 and CCR2 chemokine receptor (CD192) and cytokines (TNFA, IL6, IL10) secretion by monocytes subsets...
December 11, 2017: Cytokine
https://www.readbyqxmd.com/read/29241876/update-in-ethiopathogeny-diagnosis-and-treatment-of-the-igg4-related-disease
#19
REVIEW
Fernando Martínez-Valle, Olimpia Orozco-Gálvez, Andreu Fernández-Codina
IgG4 related disease (IgG4-RD) is probably an autoimmune pathology of unknown etiology. Diverse interactions participate in its pathogen between the adaptive and innate immune systems, activating lymphocytes B and T which trigger the inflammatory cascade, which culminates in fibrosis of the organs and their malfunction. It can affect a multitude of organs simultaneously. The diagnosis is based on the correlation of clinical findings with anatomopathological results (lymphoplasmocitary infiltrate, storiform fibrosis, obliterative phlebitis and IgG4+plasmatic cell count) and with the presence of elevated IgG4 in serum, depending on the criteria used...
December 11, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/29241813/prenatal-stress-challenge-impairs-fetal-lung-development-and-asthma-severity-sex-specifically-in-mice
#20
Dimitra E Zazara, Clara V Perani, María E Solano, Petra C Arck
Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically...
July 19, 2017: Journal of Reproductive Immunology
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