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https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#1
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28731314/desensitization-to-chemical-and-food-sensitivities-by-low-dose-immunotherapy-ascertained-by-provocation-neutralization-is-associated-with-reduced-influx-of-calcium-ions-into-lymphocytes
#2
Basant K Puri, John McLaren Howard, Jean A Monro
Background Food and chemical sensitivities have detrimental effects on health and the quality of life. The natural course of such sensitivities can potentially be altered through various types of allergen-specific immunotherapy, including low-dose immunotherapy. The molecular mechanism by which low-dose immunotherapy causes desensitization has not thus far been elucidated. While resting lymphocytes maintain a low cytosolic calcium ion concentration, antigen receptor signaling results in calcium ion influx, predominantly via store-operated calcium channels...
April 26, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28727164/the-innate-host-response-in-caries-and-periodontitis
#3
Joerg Meyle, Henrik Dommisch, Sabine Groeger, Rodrigo A Giacaman, Massimo Costalonga, Mark Herzberg
Innate immunity rapidly defends the host against infectious insults. These reactions are of limited specificity and exhaust without providing long-term protection. Functional fluids and effector molecules contribute to the defence against infectious agents, drive the immune response, and direct the cellular players. AIM: To review the literature and present a summary of current knowledge about the function of tissues, cellular players and soluble mediators of innate immunity relevant to caries and periodontitis...
July 20, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#4
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#5
J Tiraboschi, S Ray, K Patel, A Teague, M Pace, P Phalora, N Robinson, E Hopkins, J Meyerowitz, Y Wang, J Cason, S Kaye, J Sanderson, P Klenerman, S Fidler, J Frater, J Fox
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19)...
July 18, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28716576/tlr9-mediated-conditioning-of-liver-environment-is-essential-for-successful-intrahepatic-immunotherapy-and-effective-memory-recall
#6
Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Ramona F Kratzer, Florian Kreppel, Georgia Koutsoumpli, Toos Daemen, Hansjörg Hauser, Dagmar Wirth
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients...
July 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28715493/host-genetics-play-a-critical-role-in-controlling-cd8-t-cell-function-and-lethal-immunopathology-during-chronic-viral-infection
#7
Allison F Christiaansen, Megan E Schmidt, Stacey M Hartwig, Steven M Varga
Effective CD8 T cell responses are vital for the control of chronic viral infections. Many factors of the host immune response contribute to the maintenance of effector CD8 T cell responses versus CD8 T cell exhaustion during chronic infection. Specific MHC alleles and the degree of MHC heterogeneity are associated with enhanced CD8 T cell function and viral control during human chronic infection. However, it is currently unclear to what extent host genetics influences the establishment of chronic viral infection...
July 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28714470/essential-role-of-fbxl5-mediated-cellular-iron-homeostasis-in-maintenance-of-hematopoietic-stem-cells
#8
Yoshiharu Muto, Masaaki Nishiyama, Akihiro Nita, Toshiro Moroishi, Keiichi I Nakayama
Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28713869/association-of-anisocytosis-with-markers-of-immune-activation-and-exhaustion-in-treated-hiv
#9
Sadeer G Al-Kindi, David A Zidar, Grace A McComsey, Chris T Longenecker
BACKGROUND: Treated HIV infection is associated with heightened inflammation which can contribute to increased risk of cardiovascular disease (CVD). We have previously shown that anisocytosis, as measured by red cell distribution width (RDW), is independently associated with prevalent CVD in people living with HIV (PLHIV). In this study, we sought to identify immune correlates of RDW in PLHIV receiving antiretroviral therapy. METHODS: We performed a cross-sectional and longitudinal analysis of 147 virally-suppressed PLHIV, who had LDL < 130 mg/dL and evidence of heightened inflammation, in a randomized trial of statin therapy...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28711132/additional-conditions-amenable-to-observation-care
#10
REVIEW
Matthew A Wheatley
ED observation units (EDOUs) are designed for patients who require diagnostics or therapeutics beyond the initial ED visit to determine the need for hospital admission. Best evidence is that this care be delivered via ordersets or protocols. Occasionally, patients present with conditions that are amenable to EDOU care but fall outside the commonly used protocols. This article details a few of these conditions: abnormal uterine bleeding, allergic reaction, alcohol intoxication, acetaminophen overdose and sickle cell vaso-occlusive crisis...
August 2017: Emergency Medicine Clinics of North America
https://www.readbyqxmd.com/read/28710491/ageing-and-latent-cmv-infection-impact-on-maturation-differentiation-and-exhaustion-profiles-of-t-cell-receptor-gammadelta-t-cells
#11
Martine J Kallemeijn, Anne Mieke H Boots, Michèle Y van der Klift, Elisabeth Brouwer, Wayel H Abdulahad, Jan A N Verhaar, Jacques J M van Dongen, Anton W Langerak
Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708863/negative-modulation-of-suppressive-hiv-specific-regulatory-t-cells-by-il-2-adjuvanted-therapeutic-vaccine
#12
Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki
The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28707699/predict-disease-progression-from-t-cell-phenotypes-in-northern-pig-tailed-macaques-macaca-leonina-during-sivmac239-infection
#13
Ming-Xu Zhang, Hong-Yi Zheng, Jin Jiang, Jia-Hao Song, Min Chen, Yu Xiao, Xiao-Dong Lian, Tian-Zhang Song, Ren-Rong Tian, Wei Pang, Yong-Tang Zheng
Macaca leonina (northern pig-tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analyzed, for the first time, the correlations between T cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T cell count, CD4/CD8 ratio and lower plasma viral load than NPs. CD4+ T cell count and CD4/CD8 ratio decreased more sharply in NPs than in SPs...
July 14, 2017: Immunology
https://www.readbyqxmd.com/read/28706349/training-echo-state-networks-for-rotation-invariant-bone-marrow-cell-classification
#14
Philipp Kainz, Harald Burgsteiner, Martin Asslaber, Helmut Ahammer
The main principle of diagnostic pathology is the reliable interpretation of individual cells in context of the tissue architecture. Especially a confident examination of bone marrow specimen is dependent on a valid classification of myeloid cells. In this work, we propose a novel rotation-invariant learning scheme for multi-class echo state networks (ESNs), which achieves very high performance in automated bone marrow cell classification. Based on representing static images as temporal sequence of rotations, we show how ESNs robustly recognize cells of arbitrary rotations by taking advantage of their short-term memory capacity...
2017: Neural Computing & Applications
https://www.readbyqxmd.com/read/28702371/hydrogen-from-algal-biomass-a-review-of-production-process
#15
REVIEW
Archita Sharma, Shailendra Kumar Arya
Multifariousness of biofuel sources has marked an edge to an imperative energy issue. Production of hydrogen from microalgae has been gathering much contemplation right away. But, mercantile production of microalgae biofuels considering bio-hydrogen is still not practicable because of low biomass concentration and costly down streaming processes. This review has taken up the hydrogen production by microalgae. Biofuels are the up and coming alternative to exhaustible, environmentally and unsafe fossil fuels...
September 2017: Biotechnology Reports
https://www.readbyqxmd.com/read/28702032/nk-cell-exhaustion
#16
REVIEW
Jiacheng Bi, Zhigang Tian
Natural killer cells are important effector lymphocytes of the innate immune system, playing critical roles in antitumor and anti-infection host defense. Tumor progression or chronic infections, however, usually leads to exhaustion of NK cells, thus limiting the antitumor/infection potential of NK cells. In many tumors or chronic infections, multiple mechanisms might contribute to the exhaustion of NK cells, such as dysregulated NK cell receptors signaling, as well as suppressive effects by regulatory cells or soluble factors within the microenvironment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28697282/exploring-the-potential-of-natural-and-synthetic-neuroprotective-steroids-against-neurodegenerative-disorders-a-literature-review
#17
REVIEW
Ranju Bansal, Ranjit Singh
Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents...
July 11, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28696685/modeling-sequence-dependent-peptide-fluctuations-in-immunologic-recognition
#18
Cory M Ayres, Timothy P Riley, Steven A Corcelli, Brian M Baker
In cellular immunity, T cells recognize peptide antigens bound and presented by major histocompatibility complex (MHC) proteins. The motions of peptides bound to MHC play a significant role in determining immunogenicity. However, existing approaches for investigating peptide/MHC motional dynamics are challenging or of low throughput, hindering the development of algorithms for predicting immunogenicity from large databases, such as those of tumor or genetically unstable viral genomes. We addressed this by performing exhaustive molecular dynamics simulations on a large structural database of peptides bound to the most commonly expressed human class I MHC protein, HLA-A*0201...
July 11, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28692589/emerging-cancer-specific-therapeutic-aptamers
#19
Sorah Yoon, John J Rossi
PURPOSE OF REVIEW: We will describe recently discovered smart aptamers with tumor specificity, with an emphasis on targeted delivery of novel therapeutic molecules, cancer-specific biomarkers, and immunotherapy. RECENT FINDINGS: The development of cancer-specific aptamers has facilitated targeted delivery of potent therapeutic molecules to cancer cells without harming nontumoral cells. This specificity also makes it possible to discover novel cancer biomarkers. Furthermore, alternative immune-checkpoint blockade aptamers have been developed for combinational immunotherapy...
July 7, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28692536/asymptomatic-anorectal-chlamydia-trachomatis-and-neisseria-gonorrhoeae-infections-are-associated-with-systemic-cd8-t-cell-activation
#20
Vinicius A Vieira, Vivian I Avelino-Silva, Natalia B Cerqueira, Dayane A Costa, Priscilla R Costa, Ricardo P Vasconcelos, Valdez R Madruga, Ronaldo Ismério Moreira, Brenda Hoagland, Valdiléa G Veloso, Beatriz Grinsztejn, Esper G Kallás
BACKGROUND: Oral pre-exposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), are also highly prevalent. Although the presence of STI-related mucosal lesions is a known risk factor for HIV acquisition, the potential increase in risk associated with asymptomatic STIs is not completely understood. Recent data demonstrated higher T cell activation is a risk factor for sexually acquired HIV-1 infection...
July 7, 2017: AIDS
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