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https://www.readbyqxmd.com/read/29454993/in-vitro-studies-of-disease-linked-variants-of-human-trna-nucleotidyltransferase-reveal-decreased-thermal-stability-and-altered-catalytic-activity
#1
M Leibovitch, P J Hanic-Joyce, P B M Joyce
Mutations in the human TRNT1 gene encoding tRNA nucleotidyltransferase (tRNA-NT), an essential enzyme responsible for addition of the CCA (cytidine-cytidine-adenosine) sequence to the 3'-termini of tRNAs, have been linked to disease phenotypes including congenital sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD) or retinitis pigmentosa with erythrocyte microcytosis. The effects of these disease-linked mutations on the structure and function of tRNA-NT have not been explored...
February 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29453226/modeling-the-human-bone-marrow-niche-in-mice-from-host-bone-marrow-engraftment-to-bioengineering-approaches
#2
REVIEW
Ander Abarrategi, Syed A Mian, Diana Passaro, Kevin Rouault-Pierre, William Grey, Dominique Bonnet
Xenotransplantation of patient-derived samples in mouse models has been instrumental in depicting the role of hematopoietic stem and progenitor cells in the establishment as well as progression of hematological malignancies. The foundations for this field of research have been based on the development of immunodeficient mouse models, which provide normal and malignant human hematopoietic cells with a supportive microenvironment. Immunosuppressed and genetically modified mice expressing human growth factors were key milestones in patient-derived xenograft (PDX) models, highlighting the importance of developing humanized microenvironments...
February 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29447279/regulatory-t-cells-in-retroviral-infections
#3
REVIEW
Kim J Hasenkrug, Claire A Chougnet, Ulf Dittmer
Tight regulation of immune responses is not only critical for preventing autoimmune diseases but also for preventing immunopathological damage during infections in which overactive immune responses may be more harmful for the host than the pathogen itself. Regulatory T cells (Tregs) play a critical role in this regulation, which was discovered using the Friend retrovirus (FV) mouse model. Subsequent FV studies revealed basic biological information about Tregs, including their suppressive activity on effector cells as well as the molecular mechanisms of virus-induced Treg expansion...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29442899/highly-efficient-glioma-targeting-of-tat-peptide-tta1-aptamer-polyephylene-glycol-modified-gelatin-siloxane-nanoparticles
#4
Xiao-Ning Lin, Xinli Tian, Wang Li, Jin Sun, Feng Wei, Wei Feng, Zhi-Chun Huang, Xin-Hua Tian
Gliomas are the most common type of intracranial malignant tumor; however, current treatment approaches are often ineffective due to limited penetration of genes or drugs through the blood-brain barrier (BBB). Here we describe the synthesis of gelatin-siloxane nanoparticles (GS NPs) as candidate gene carriers through a two-step sol-gel process. To increase the efficiency of glioma targeting, human immunodeficiency virus-derived Tat, tumor-targeting aptamer (TTA)1, and polyethylene glycol (PEG) were conjugated to the GS NPs to generate Tat-TTA1-PEG-GS NPs...
April 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29437536/opioid-stewardship-in-otolaryngology-state-of-the-art-review
#5
John D Cramer, Brad Wisler, And Christopher J Gouveia
Objective The United States is facing an epidemic of opioid addiction. Deaths from opioid overdose have quadrupled in the past 15 years and now surpass annual deaths during the height of the human immunodeficiency virus epidemic. There is a link between opioid prescriptions after surgery, opioid misuse, opioid diversion, and use of other drugs of abuse. As surgeons, otolaryngologists contribute to this crisis. Our objective is to outline the risk of abuse from opioids in the management of acute postoperative pain in otolaryngology-head and neck surgery (OHNS) and strategies to avoid misuse...
February 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29434589/modeling-human-antitumor-responses-in-vivo-using-umbilical-cord-blood-engrafted-mice
#6
REVIEW
Nicholas A Zumwalde, Jenny E Gumperz
Mice engrafted with human immune cells offer powerful in vivo model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, de novo neoplastic transformation of the human B cells can be induced in vivo in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29425965/the-small-heat-shock-proteins-especially-hspb4-and-hspb5-are-promising-protectants-in-neurodegenerative-diseases
#7
REVIEW
Zhihui Zhu, Georg Reiser
Small heat shock proteins (sHsps) are a group of proteins with molecular mass between 12 and 43 kDa. Currently, 11 members of this family have been classified, namely HspB1 to HspB11. HspB1, HspB2, HspB5, HspB6, HspB7, and HspB8, which are expressed in brain have been observed to be related to the pathology of neurodegenerative diseases, including Parkinson's, Alzheimer's, Alexander's disease, multiple sclerosis, and human immunodeficiency virus-associated dementia. Specifically, sHsps interact with misfolding and damaging protein aggregates, like Glial fibrillary acidic protein in AxD, β-amyloid peptides aggregates in Alzheimer's disease, Superoxide dismutase 1 in Amyotrophic lateral sclerosis and cytosine-adenine-guanine/polyglutamine (CAG/PolyQ) in Huntington's disease, Spinocerebellar ataxia type 3, Spinal-bulbar muscular atrophy, to reduce the toxicity or increase the clearance of these protein aggregates...
February 6, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29425816/recent-updates-for-designing-ccr5-antagonists-as-anti-retroviral-agents
#8
REVIEW
Harshil R Shah, Jignasa Ketan Savjani
The healthcare system faces various challenges in human immunodeficiency virus (HIV) therapy due to resistance to Anti-Retroviral Therapy (ART) as a consequence of the evolutionary process. Despite the success of antiretroviral drugs like Zidovudine, Zalcitabine, Raltegravir WHO ranks HIV as one of the deadliest diseases with a mortality of one million lives in 2016. Thus, there emerges an urgency of developing a novel anti-retroviral agent that combat resistant HIV strains. The clinical development of ART from a single drug regimen to current triple drug combination is very slow...
January 31, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29425101/exceptional-potency-and-structural-basis-of-a-t1249-derived-lipopeptide-fusion-inhibitor-against-hiv-1-hiv-2-and-simian-immunodeficiency-virus
#9
Yuanmei Zhu, Xiujuan Zhang, Xiaohui Ding, Huihui Chong, Sheng Cui, Jinsheng He, Xinquan Wang, Yuxian He
Enfuvirtide (T20) is the only viral fusion inhibitor approved for clinical use, but it has relatively weak anti-HIV activity and easily induces drug resistance. In succession to T20, T1249 has been designed as a 39-mer peptide composed of amino acid sequences derived from HIV-1, HIV-2, and simian immunodeficiency virus (SIV); however, its development has been suspended due to formulation difficulties. We recently developed a T20-based lipopeptide (LP-40) showing greatly improved pharmaceutical properties. Here, we generated a T1249-based lipopeptide, termed LP-46, by replacing its C-terminal tryptophan-rich sequence with fatty acid...
February 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29424324/nano-medicine-as-a-newly-emerging-approach-to-combat-human-immunodeficiency-virus-hiv
#10
Muthupandian Saravanan, Tsehaye Asmalash, Atsebaha Gebrekidan, Dawit Gebreegziabiher, Tadele Araya, Haftamu Hilekiros, Hamed Barabadi, Kumaresan Ramanathan
BACKGROUND: Human Immuno deficiency Virus (HIV) infection has attained pandemic level due to its complexity on both the HIV infection cycle and on the targets for drug delivery. This limits medication and consequently requires prominent and promising drug delivery systems to be invented. Notably, various nanomaterial have been studied to enhance effective delivery of the antiretroviral drugs for HIV prevention, diagnosis and cure. Some of these nanomaterials are liposomes, dendrimers, inorganic nanoparticles (NPs), polymeric micelles, natural and synthetic polymers...
February 8, 2018: Pharmaceutical Nanotechnology
https://www.readbyqxmd.com/read/29420696/sensitivity-analyses-for-misclassification-of-cause-of-death-in-the-parametric-g-formula
#11
Jessie K Edwards, Stephen R Cole, Richard D Moore, W Christopher Mathews, Mari Kitahata, Joseph J Eron
Cause-specific mortality is an important outcome in studies of interventions to improve survival, yet causes of death can be misclassified. Here, we present an approach to perform sensitivity analyses for misclassification of cause of death in the parametric g-formula. The g-formula is useful method to estimate effects of interventions in epidemiologic research because it appropriately accounts for time-varying confounding affected by prior treatment and can estimate risk under dynamic treatment plans. We illustrate our approach using an example comparing acquired immune deficiency syndrome (AIDS)-related mortality under immediate and delayed treatment strategies in a cohort of therapy-naïve adults entering care for human immunodeficiency virus in the United States...
February 6, 2018: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29415435/review-of-current-cell-penetrating-antibody-developments-for-hiv-1-therapy
#12
REVIEW
Muhamad Alif Che Nordin, Sin-Yeang Teow
The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases...
February 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29413883/the-role-of-regulatory-t-cells-in-immunopathogenesis-and-immunotherapy-of-viral-infections
#13
REVIEW
Ahmad Karkhah, Mostafa Javanian, Soheil Ebrahimpour
Two hepatotropic viruses hepatitis C virus (HCV) and hepatitis B virus (HBV) have been considered as the main cause of chronic viral infections. In addition, human immunodeficiency virus (HIV) attacks the immune system by eradication of some white blood cell (T-helper cell). The role of Tregs in HCV, HBV and HIV infections ranges from suppressing antiviral T cell responses to protecting tissues as liver and immune cells from immune mediated injury. In this review, we discuss the influence of regulatory T cells in immunopathology of specific viral infections including HCV, HBV and HIV by focusing on targeting Tregs as novel approach in vaccinology against viral infections...
January 29, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29412887/lymphoma-and-pathology-in-sub-saharan-africa-current-approaches-and-future-directions
#14
REVIEW
Tamiwe Tomoka, Nathan D Montgomery, Eric Powers, Bal Mukunda Dhungel, Elizabeth A Morgan, Maurice Mulenga, Satish Gopal, Yuri Fedoriw
The care of patients with lymphoma relies heavily on accurate tissue diagnosis and classification. In sub-Saharan Africa, where lymphoma burden is increasing because of population growth, aging, and continued epidemic levels of human immunodeficiency virus infection, diagnostic pathology services are limited. This article summarizes lymphoma epidemiology, current diagnostic capacity, and obstacles and opportunities for improving practice in the region.
March 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29410245/engineered-humanized-bone-organs-maintain-human-hematopoiesis-in-vivo
#15
Kristin Fritsch, Sébastien Pigeot, Xiaomin Feng, Paul E Bourgine, Timm Schroeder, Ivan Martin, Markus G Manz, Hitoshi Takizawa
Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) environment, the so-called HSC niche, that provides pivotal factors for their maintenance. While the cellular and molecular components of the mouse BM HSC niche have been extensively studied using genetically modified animals, relatively little is known about the counterpart human BM niche components. We have previously shown with a developmental tissue engineering approach that human adult BM-derived mesenchymal stromal cells (MSCs) can develop into human bone organs (so-called ossicles) through endochondral ossification in vivo, and that these human ossicles are able to maintain functional mouse HSCs...
February 2, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29408450/effect-of-25-hydroxycholesterol-in-viral-membrane-fusion-insights-on-hiv-inhibition
#16
Bárbara Gomes, Sónia Gonçalves, Anibal Disalvo, Axel Hollmann, Nuno C Santos
Recently, it was demonstrated that 25-hydroxycholesterol (25HC), an oxidized cholesterol derivative, inhibits human immunodeficiency virus type 1 (HIV) entry into its target cells. However, the mechanisms involved in this action have not yet been established. The aim of this work was to study the effects of 25HC in biomembrane model systems and at the level of HIV fusion peptide (HIV-FP). Integration of different biophysical approaches was made in the context of HIV fusion process, to clarify the changes at membrane level due to the presence of 25HC that result in the suppressing viral infection...
February 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29400602/identification-of-sp1683-as-a-pneumococcal-protein-that-is-protective-against-nasopharyngeal-colonization
#17
Leen Moens, Philippe Hermand, Tine Wellens, Greet Wuyts, Rita Derua, Etienne Waelkens, Carine Ysebaert, Fabrice Godfroid, Xavier Bossuyt
Serotype-independent protein-based pneumococcal vaccines represent attractive alternatives to capsular polysaccharide-based vaccines. The aim of this study was to identify novel immunogenic proteins from Streptococcus pneumoniae that may be used in protein-based pneumococcal vaccine. An immunoproteomics approach and a humanized severe combined immunodeficient mouse model were used to identify S. pneumoniae proteins that are immunogenic for the human immune system. Among the several proteins identified, SP1683 was selected, recombinantly produced, and infection and colonization murine models were used to evaluate the capacity of SP1683 to elicit protective responses, in comparison to known pneumococcal immunogenic proteins (PhtD and detoxified pneumolysin, dPly)...
February 5, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29393912/common-variable-immunodeficiency-and-gastric-malignancies
#18
REVIEW
Patrizia Leone, Angelo Vacca, Franco Dammacco, Vito Racanelli
Common variable immunodeficiency (CVID) is an immunodeficiency disorder with a high incidence of gastrointestinal manifestations and an increased risk of gastric carcinoma and lymphoma. This review discusses the latest advancements into the immunological, clinical and diagnostic aspects of gastric malignancies in patients with CVID. The exact molecular pathways underlying the relationships between CVID and gastric malignancies remain poorly understood. These include genetics, immune dysregulation and chronic infections by Helicobacter pylori ...
February 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29384848/economic-evaluation-of-weekends-off-antiretroviral-therapy-for-young-people-in-11-countries
#19
Luis Enrique Tierrablanca, Jessica Ochalek, Deborah Ford, Ab Babiker, Diana Gibb, Karina Butler, Anna Turkova, Susan Griffin, Paul Revill
OBJECTIVES: To analyze the cost effectiveness of short-cycle therapy (SCT), where patients take antiretroviral (ARV) drugs 5 consecutive days a week and have 2 days off, as an alternative to continuous ARV therapy for young people infected with human immunodeficiency virus (HIV) and taking efavirenz-based first-line ARV drugs. METHODS: We conduct a hierarchical cost-effectiveness analysis based on data on clinical outcomes and resource use from the BREATHER trial...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29384110/systematic-investigation-for-underlying-causes-of-recurrent-infections-in-children-surveillance-of-primary-immunodeficiency
#20
S Yousefzadegan, M Tavakol, H Abolhassani, A Nadjafi, S Mansouri, R Yazdani, G Azizi, B Negahdari, N Rezaei, A Aghamohammadi
Recurrent infections seem to be a common complaint in children who are referred to general practitioners and pediatricians offices. Detection of primary immunodeficiencies (PID) etiology is very important for achieving appropriate diagnosis and treatment of these patients. The absence of appropriate treatment could lead to subsequent complications, in a hospital inpatient and/or outpatient settings. This study was performed in a group of children with recurrent infections to identify patients with underlying PID...
November 21, 2017: European Annals of Allergy and Clinical Immunology
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