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Translational immunology

Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
March 14, 2018: Human Molecular Genetics
Neill J Liptrott, Marco Giardiello, Tom O McDonald, Steve P Rannard, Andrew Owen
BACKGROUND: Recent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. Other SDN formulations are being studied for parenteral administration, either as intramuscular long-acting formulations, or for direct administration intravenously. The interaction of nanoparticles with the immunological and haematological systems can be a major barrier to successful translation but has been understudied for SDN formulations...
March 15, 2018: Journal of Nanobiotechnology
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
Zlatka Georgieva Dobreva, Boncho Grigorov Grigorov, Spaska Angelova Stanilova
BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-α) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-α has an inducible expression, IL-18 is translated as an inactive protein and required proteolytic cleavage by Casp-1 in inflammasome complexes. AIM: To investigate the effect of the histone deacetylases inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on the gene expression and secretion of both cytokines, IL-18 and TNF-α, according to their contribution to the cancer development and anticancer immunity...
February 15, 2018: Open Access Macedonian Journal of Medical Sciences
V Venturi, T Masek, M Pospisek
Elevated levels of eukaryotic initiation factor 4E (eIF4E) are implicated in neoplasia, with cumulative evidence pointing to its role in the etiopathogenesis of hematological diseases. As a node of convergence for several oncogenic signaling pathways, eIF4E has attracted a great deal of interest from biologists and clinicians whose efforts have been targeting this translation factor and its biological circuits in the battle against leukemia. The role of eIF4E in myeloid leukemia has been ascertained and drugs targeting its functions have found their place in clinical trials...
March 12, 2018: Physiological Research
Ana Laura Fitas, Catarina Martins, Luís Miguel Borrego, Lurdes Lopes, Anne Jörns, Sigurd Lenzen, Catarina Limbert
AIMS/HYPOTHESIS: Type 1 diabetes (T1D) develops in distinct stages, before and after disease onset. Whether the natural course translates into different immunologic patterns is still uncertain. This study aimed at identifying peripheral immune patterns at key time-points, in T1D children undergoing remission phase. METHODS: Children with new-onset T1D and healthy age and gender-matched controls were recruited at a paediatric hospital. Peripheral blood samples were evaluated by flow cytometry at three longitudinal time-points: onset (T1), remission phase (T2) and established disease (T3)...
March 12, 2018: Pediatric Diabetes
Eros Marín, Maria Cristina Cuturi, Aurélie Moreau
Over the past century, solid organ transplantation has been improved both at a surgical and postoperative level. However, despite the improvement in efficiency, safety, and survival, we are still far from obtaining full acceptance of all kinds of allograft in the absence of concomitant treatments. Today, transplanted patients are treated with immunosuppressive drugs (IS) to minimize immunological response in order to prevent graft rejection. Nevertheless, the lack of specificity of IS leads to an increase in the risk of cancer and infections...
2018: Frontiers in Immunology
A Borreca, V Latina, V Corsetti, S Middei, S Piccinin, F Della Valle, R Bussani, M Ammassari-Teule, R Nisticò, P Calissano, G Amadoro
The NH2 tau 26-44 aa (i.e., NH2 htau) is the minimal biologically active moiety of longer 20-22-kDa NH2 -truncated form of human tau-a neurotoxic fragment mapping between 26 and 230 amino acids of full-length protein (htau40)-which is detectable in presynaptic terminals and peripheral CSF from patients suffering from AD and other non-AD neurodegenerative diseases. Nevertheless, whether its exogenous administration in healthy nontransgenic mice is able to elicit a neuropathological phenotype resembling human tauopathies has not been yet investigated...
March 5, 2018: Molecular Neurobiology
Roberta Barachetti, Elisabetta Villa, Mario Barbarini
The introduction of solid food is necessary for any infant in order to provide adequate nutrition because when they grow up milk is insufficient for their nutritional needs. Infants born preterm have increased nutritional requirements. The high nutrient demands as well as the organ immaturity of preterm infants combine to render it difficult to achieve dietary intakes that will allow preterm infants to match their in utero growth rates. Current guidelines for the introduction of solid food to term infants cannot be directly translated to preterm infants...
December 22, 2017: La Pediatria Medica e Chirurgica: Medical and Surgical Pediatrics
Andreas Habertheuer, Laxminarayana Korutla, Susan Rostami, Sanjana Reddy, Priti Lal, Ali Naji, Prashanth Vallabhajosyula
OBJECTIVE: In heart transplantation, there is a critical need for development of biomarkers to noninvasively monitor cardiac allografts for immunologic rejection or injury. Exosomes are tissue-specific nanovesicles released into circulation by many cell types. Their profiles are dynamic, reflecting conditional changes imposed on their tissue counterparts. We proposed that a transplanted heart releases donor-specific exosomes into the recipient's circulation that are conditionally altered during immunologic rejection...
February 1, 2018: Journal of Thoracic and Cardiovascular Surgery
M Giuliani, E Bartolini, B Galli, L Santini, P Lo Surdo, F Buricchi, M Bruttini, B Benucci, N Pacchiani, L Alleri, D Donnarumma, W Pansegrau, I Peschiera, I Ferlenghi, R Cozzi, N Norais, M M Giuliani, D Maione, M Pizza, R Rappuoli, O Finco, V Masignani
4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studies, we have isolated a panel of human monoclonal antibodies from adult vaccinees. Based on the Ig-gene sequence of the variable region, 37 antigen-specific monoclonal antibodies were identified and produced as recombinant Fab fragments, and a subset also produced as full length recombinant IgG1 and functionally characterized...
February 27, 2018: Scientific Reports
Sanchita Bhattacharya, Patrick Dunn, Cristel G Thomas, Barry Smith, Henry Schaefer, Jieming Chen, Zicheng Hu, Kelly A Zalocusky, Ravi D Shankar, Shai S Shen-Orr, Elizabeth Thomson, Jeffrey Wiser, Atul J Butte
Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components-Private Data, Shared Data, Data Analysis, and Resources-for data archiving, dissemination, analyses, and reuse...
February 27, 2018: Scientific Data
Daniel Martinho-Dias, Bernardo Sousa-Pinto, Júlio Botelho-Souza, António Soares, Luís Delgado, João Almeida Fonseca
We performed a MeSH term-based bibliometric analysis aiming to assess the publication trends of EAACI journals, namely Allergy, Pediatric Allergy and Immunology (PAI) (from 1990 to 2015) and Clinical and Translational Allergy (CTA) (from its inception in 2011 to 2015). We also aimed to discuss the impact of the creation of CTA in the publication topics of Allergy and PAI. We analysed a total of 1973 articles and 23,660 MeSH terms. Most MeSH terms in the three journals fell in the category of "basic immunology and molecular biology" (BIMB)...
2018: Clinical and Translational Allergy
Elizabeth A Kuczynski, Janna Krueger, Annabelle Chow, Ping Xu, Shan Man, Yogi Sundaravadanam, Jessica K Miller, Paul M Krzyzanowski, Robert S Kerbel
A recurring historical finding in cancer drug development is encouraging anti-tumor effects observed in tumor-bearing mice which fail to translate into the clinic. An intriguing exception to this pattern is immune checkpoint therapy, as the sustained tumor regressions observed in subsets of cancer patients are rare in mice. Reasoning that this may be due in part to relatively low mutational loads of mouse tumors, we mutagenized transplantable mouse tumor cell lines EMT-6/P, B16F1, RENCA, CT26 and MC38 in vitro with methylnitro-nitrosoguanidine (MNNG) or ethylmethane sulfonate (EMS) and tested their responsiveness to PD-L1 blockade...
February 26, 2018: Molecular Cancer Therapeutics
Jacques Descotes, Linda Allais, Philippe Ancian, Henrik Duelund Pedersen, Claire Friry-Santini, Antonio Iglesias, Tina Rubic-Schneider, Hollie Skaggs, Peter Vestbjerg
There is a growing need to consider non-rodent species for the immunological safety evaluation of drug candidates. The EU Framework-6 RETHINK Project demonstrated that the Göttingen Minipig is a relevant animal model for regulatory toxicology studies. Extensive knowledge on the immune system of domestic pigs is available and fewer differences from humans have been identified as compared to other species, such as mice or non-human primates. Minipig data are too scarce to allow for claiming full immunological comparability with domestic pigs...
February 23, 2018: Regulatory Toxicology and Pharmacology: RTP
Sara Azizian, Fatemeh Khatami, Khashayar Modaresifar, Nariman Mosaffa, Habibollah Peirovi, Lobat Tayebi, Soheyl Bahrami, Heinz Redl, Hassan Niknejad
Placenta-derived amniotic epithelial cells (AECs), a great cell source for tissue engineering and stem cell therapy, are immunologically inert in their native state; however, immunological changes in these cells after culture and differentiation have challenged their applications. The aim of this study was to investigate the effect of 2D and 3D scaffolds on human lymphocyte antigens (HLA) expression by AECs. The effect of different preparation parameters including pre-freezing time and temperature was evaluated on 3D chitosan-gelatine scaffolds properties...
February 23, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Brian C Gilger
Ocular inflammatory diseases, such as dry eye and uveitis, are common, painful, difficult to treat, and may result in vision loss or blindness. Ocular side effects from the use of antiinflammatory drugs (such as corticosteroids or nonsteroidal antiinflammatories) to treat ocular inflammation have prompted development of more specific and safer medications to treat inflammatory and immune-mediated diseases of the eye. To assess the efficacy and safety of these new therapeutics, appropriate immune-relevant animal models of ocular inflammation are needed...
February 21, 2018: ILAR Journal
M Ilie, J Benzaquen, V Hofman, S Lassalle, N Yazbeck, S Leroy, S Heeke, C Bence, B Mograbi, N Glaichenhaus, C H Marquette, P Hofman
Immunotherapy aims to amplify the anticancer immune response through reactivation of the lymphocytic response raised against several tumor neo-antigens. To obtain an effective immune response, this therapeutic approach requires that a number of immunological checkpoints be passed, such as the activation of excitatory costimulatory signals or the avoidance of coinhibitory molecules. Among the immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its receptor PD-L1 has received much attention because of remarkable efficacy in numerous clinical trials for various cancer types, including non-small cell lung cancer (NSCLC)...
February 21, 2018: Current Molecular Medicine
Amanda J Brinkworth, Mark R Wildung, Rey A Carabeo
Iron is essential for growth and development of Chlamydia . Its long-term starvation in cultured mammalian cells leads to production of aberrant noninfectious chlamydial forms, also known as persistence. Immediate transcriptional responses to iron limitation have not been characterized, leaving a knowledge gap of how Chlamydia regulates its response to changes in iron availability. We used the fast-chelating agent 2,2'-bipyridyl (BPDL) to homogeneously starve Chlamydia trachomatis serovar L2 of iron, starting at 6 or 12 h postinfection...
January 2018: MSystems
Bowen Li, Zhefan Yuan, Peng Zhang, Andrew Sinclair, Priyesh Jain, Kan Wu, Caroline Tsao, Jingyi Xie, Hsiang-Chieh Hung, Xiaojie Lin, Tao Bai, Shaoyi Jiang
For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself...
February 19, 2018: Advanced Materials
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