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Human Challenge Model

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https://www.readbyqxmd.com/read/28930982/development-of-a-human-preclinical-model-of-osteoclastogenesis-from-peripheral-blood-monocytes-co-cultured-with-breast-cancer-cell-lines
#1
Laura Mercatali, Chiara Spadazzi, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Alberto Bongiovanni, Federica Recine, Dino Amadori, Toni Ibrahim
The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We developed an in vitro fully human preclinical model of a co-culture of breast cancer cells and monocytes undergoing differentiation towards osteoclasts. We optimized a model of osteoclastogenesis starting from a sample of peripheral blood collected from healthy donors. Peripheral blood mononuclear cells (PBMCs) were first separated by density gradient centrifugation, seeded at a high density and induced to differentiate by adding two growth factors (GFs): receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF)...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930519/divergent-impact-of-gender-in-advancement-of-liver-injuries-diseases-and-carcinogenesis
#2
Subhrajit Biswas, Sampa Ghose
Several investigations have revealed that liver diseases exhibit gender biases, but identifying the root causes of such biases has been challenging. Evidence of gender differences in liver function is present from the early stage of embryonic development. The differences in access to care and treatment as well as diagnostic deliberation may affect gender-specific differences in liver disease progression. Apart from the pathogenesis, xenobiotic metabolism, immune responses, gene expressions, mitochondrial function, lipid composition, and enzyme activities also differ in this sexually dimorphic organ...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28928775/assessment-of-safety-and-functional-efficacy-of-stem-cell-based-therapeutic-approaches-using-retinal-degenerative-animal-models
#3
REVIEW
Tai-Chi Lin, Magdalene J Seiler, Danhong Zhu, Paulo Falabella, David R Hinton, Dennis O Clegg, Mark S Humayun, Biju B Thomas
Dysfunction and death of retinal pigment epithelium (RPE) and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an "immune privileged" site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula). Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors) into the vitreous cavity or subretinal space has been well established...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28928765/emerging-challenges-and-opportunities-for-education-and-research-in-weed-science
#4
REVIEW
Bhagirath S Chauhan, Amar Matloob, Gulshan Mahajan, Farhena Aslam, Singarayer K Florentine, Prashant Jha
In modern agriculture, with more emphasis on high input systems, weed problems are likely to increase and become more complex. With heightened awareness of adverse effects of herbicide residues on human health and environment and the evolution of herbicide-resistant weed biotypes, a significant focus within weed science has now shifted to the development of eco-friendly technologies with reduced reliance on herbicides. Further, with the large-scale adoption of herbicide-resistant crops, and uncertain climatic optima under climate change, the problems for weed science have become multi-faceted...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28928215/influenza-virus-hemagglutinin-stalk-specific-antibodies-in-human-serum-are-a-surrogate-marker-for-in-vivo-protection-in-a-serum-transfer-mouse-challenge-model
#5
Henning Jacobsen, Madhusudan Rajendran, Angela Choi, Haakon Sjursen, Karl A Brokstad, Rebecca J Cox, Peter Palese, Florian Krammer, Raffael Nachbagauer
The immunogenicity of current influenza virus vaccines is assessed by measuring an increase of influenza virus-specific antibodies in a hemagglutination inhibition assay. This method exclusively measures antibodies against the hemagglutinin head domain. While this domain is immunodominant, it has been shown that hemagglutination inhibition titers do not always accurately predict protection from disease. In addition, several novel influenza virus vaccines that are currently under development do not target the hemagglutinin head domain, but rather more conserved sites, including the hemagglutinin stalk...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28928207/a-perfect-storm-increased-colonization-and-failure-of-vaccination-leads-to-severe-secondary-bacterial-infection-in-influenza-virus-infected-obese-mice
#6
Erik A Karlsson, Victoria A Meliopoulos, Nicholas C van de Velde, Lee-Ann van de Velde, Beth Mann, Geli Gao, Jason Rosch, Elaine Tuomanen, Jon McCullers, Peter Vogel, Stacey Schultz-Cherry
Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28927931/polyurethane-foam-scaffold-as-in-vitro-model-for-breast-cancer-bone-metastasis
#7
Valentina Angeloni, Nicola Contessi, Cinzia De Marco, Serena Bertoldi, Maria Cristina Tanzi, Maria Grazia Daidone, Silvia Farè
Breast cancer (BC) represents the most incident cancer case in women (29%), with high mortality rate. Bone metastasis occurs in 20-50% cases and, despite advances in BC research, the interactions between tumor cells and the metastatic microenvironment are still poorly understood. In vitro 3D models gained great interest in cancer research, thanks to the reproducibility, the 3D spatial cues and associated low costs, compared to in vivo and 2D in vitro models. In this study, we investigated the suitability of a poly-ether-urethane (PU) foam as 3D in vitro model to study the interactions between BC tumor-initiating cells and the bone microenvironment...
September 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28927422/proximity-to-vector-breeding-site-and-risk-of-plasmodium-vivax-infection-a-prospective-cohort-study-in-rural-ethiopia
#8
Alexander Nissen, Jackie Cook, Eskindir Loha, Bernt Lindtjørn
BACKGROUND: Despite falling incidence and mortality since the turn of the century, malaria remains an important global health challenge. In the future fight against malaria, greater emphasis will have to be placed on understanding and addressing malaria caused by the Plasmodium vivax parasite. Unfortunately, due to years of neglect and underfunding, there are currently many gaps in knowledge of P. vivax malaria. The aims of the present study were to explore the association between distance to vector breeding site and P...
September 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28923841/a-novel-notch-yap-circuit-drives-stemness-and-tumorigenesis-in-embryonal-rhabdomyosarcoma
#9
Katherine K Slemmons, Lisa E S Crose, Stefan Riedel, Manuela Sushnitha, Brian C Belyea, Corinne M Linardic
Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft tissue sarcoma of childhood. While low and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival of <30%, a statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS)...
September 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28923102/workshop-on-challenges-insights-and-future-directions-for-mouse-and-humanized-models-in-cancer-immunology-and-immunotherapy-a-report-from-the-associated-programs-of-the-2016-annual-meeting-for-the-society-for-immunotherapy-of-cancer
#10
Andrew Zloza, A Karolina Palucka, Lisa M Coussens, Philip J Gotwals, Mark B Headley, Elizabeth M Jaffee, Amanda W Lund, Arlene H Sharpe, Mario Sznol, Derek A Wainwright, Kwok-Kin Wong, Marcus W Bosenberg
Understanding how murine models can elucidate the mechanisms underlying antitumor immune responses and advance immune-based drug development is essential to advancing the field of cancer immunotherapy. The Society for Immunotherapy of Cancer (SITC) convened a workshop titled, "Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy" as part of the SITC 31st Annual Meeting and Associated Programs on November 10, 2016 in National Harbor, MD. The workshop focused on key issues in optimizing models for cancer immunotherapy research, with discussions on the strengths and weaknesses of current models, approaches to improve the predictive value of mouse models, and advances in cancer modeling that are anticipated in the near future...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922956/dmts-is-an-effective-treatment-in-both-inhalation-and-injection-models-for-cyanide-poisoning-using-unanesthetized-mice
#11
Susan M DeLeon, Jason D Downey, Diane M Hildenberger, Melissa O Rhoomes, Lamont Booker, Gary A Rockwood, Kelly A Basi
CONTEXT: Cyanide (CN) is a metabolic poison, halting ATP synthesis by inhibiting complex IV of the electron transport chain. If exposed at high enough concentrations, humans and most animals can die within minutes. Because time is a crucial factor in survival of CN poisoning, a rapidly bioavailable, nontoxic, easy to administer CN medical countermeasure could improve morbidity/mortality in a mass CN exposure scenario. The most likely route of exposure to CN is via inhalation. OBJECTIVE: This study examined the efficacy of a new formulation for dimethyl trisulfide (DMTS), a countermeasure which has shown promise as a treatment for CN poisoning, using both inhalation and injection models of CN exposure...
September 19, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28922951/a-retrospective-study-of-cytokine-profiles-changes-in-mice-with-fviii-inhibitor-development-after-aav-mediated-gene-therapy-in-hemophilia-a-mouse-model
#12
Junjiang Sun, Zhenhua Yuan, Yasmina L Abajas, Dorreen E Szollosi, Genlin Hu, Baolai Hua, Xiao Xiao, Chengwen Li
The development of inhibitory autoantibodies to the infused clotting factor VIII is a major complication for severe hemophilia A management. Novel therapy options for hemophilia have significantly progressed in the last decade and a gene therapy cure for hemophilia is translating into reality. However, mechanistic studies of FVIII autoantibodies (FVIII inhibitors) have lagged behind and remain a challenge for both protein replacement and gene therapy. FVIII inhibitor formation is assumed to be a classical T cell-dependent immune response in which cytokines/chemokines play an important role...
September 19, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28922428/diminished-neutrophil-extracellular-trap-net-formation-is-a-novel-innate-immune-deficiency-induced-by-acute-ethanol-exposure-in-polymicrobial-sepsis-which-can-be-rescued-by-cxcl1
#13
Liliang Jin, Sanjay Batra, Samithamby Jeyaseelan
Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that acute alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28922426/a-dna-vaccine-for-crimean-congo-hemorrhagic-fever-protects-against-disease-and-death-in-two-lethal-mouse-models
#14
Aura R Garrison, Charles J Shoemaker, Joseph W Golden, Collin J Fitzpatrick, John J Suschak, Michelle J Richards, Catherine V Badger, Carolyn M Six, Jacqueline D Martin, Drew Hannaman, Marko Zivcec, Eric Bergeron, Jeffrey W Koehler, Connie S Schmaljohn
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models...
September 18, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28921966/tool-for-rapid-analysis-of-glycopeptide-by-permethylation-trap-via-one-pot-site-mapping-and-glycan-analysis
#15
Asif Shajahan, Nitin Tatyaso Supekar, Christian Heiss, Mayumi Ishihara, Parastoo Azadi
To overcome the challenges in the analysis of protein glycosylation, we have developed a comprehensive and universal tool through permethylation of glycopeptides and their tandem mass spectrometric analysis. This method has the potential to simplify glycoprotein analysis by integrating glycan sequencing and glycopeptide analysis in a single experiment. Moreover, glycans with unique glycosidic linkages, particularly from prokaryotes, which are resistant to enzymatic or chemical release, could also be detected and analyzed by this methodology...
September 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28921822/construction-of-human-induced-pluripotent-stem-cell-derived-oriented-bone-matrix-microstructure-by-using-in-vitro-engineered-anisotropic-culture-model
#16
Ryosuke Ozasa, Aira Matsugaki, Yoshihiro Isobe, Taro Saku, Hui-Suk Yun, Takayoshi Nakano
Bone tissue has anisotropic microstructure based on collagen/biological apatite orientation, which plays essential roles in the mechanical and biological functions of bone. However, obtaining an appropriate anisotropic microstructure during the bone regeneration process remains a great challenging. A powerful strategy for the control of both differentiation and structural development of newly-formed bone is required in bone tissue engineering, in order to realize functional bone tissue regeneration. In this study, we developed a novel anisotropic culture model by combining human induced pluripotent stem cells (hiPSCs) and artificially-controlled oriented collagen scaffold...
September 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28920716/transposons-moving-forward-from-preclinical-studies-to-clinical-trials
#17
Jaitip Tipanee, Thierry VandenDriessche, Marinee K Chuah
Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein...
August 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28919994/effect-of-entinostat-on-nk-cell-mediated-cytotoxicity-against-osteosarcoma-cells-and-osteosarcoma-lung-metastasis
#18
Simin Kiany, Gangxiong Huang, Eugenie S Kleinerman
There is a crucial need for a new therapeutic approach for osteosarcoma (OS) lung metastasis since this disease remains the main cause of mortality in OS. We previously demonstrated that natural killer (NK) cell therapy has minimal efficacy against OS metastasis. This study determined whether the histone deacetylase inhibitor entinostat could immunosensitize OS cells to NK cell lysis and increases the efficacy of NK cell therapy for OS lung metastasis. Entinostat upregulated ligands for NK cell-activating receptors (major histocompatibility complex [MHC] class I polypeptide-related chain A [MICA] and B [MICB]; UL16 binding proteins 1, 2, 5, and 6; and CD155) on OS cells both in vitro and in vivo and led to more susceptibility to NK cell-mediated cytotoxicity in vitro...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919812/the-effect-of-local-topical-analgesics-on-incisional-pain-in-a-pig-model
#19
David Castel, Itai Sabbag, Sigal Meilin
Interest in the development of new topical/local drug administration for blocking pain at peripheral sites, with maximum drug activity and minimal systemic effects, is on the rise. In the review article by Kopsky and Stahl, four critical barriers in the process of research and development of topical analgesics were indicated. The active pharmaceutical ingredient (API) and the formulation are among the major challenges. The road to the development of such drugs passes through preclinical studies. These studies, if planned correctly, should serve as guidance for choosing the right API and formulation...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28918056/the-therapeutic-potential-of-crispr-cas9-systems-in-oncogene-addicted-cancer-types-virally-driven-cancers-as-a-model-system
#20
REVIEW
Luqman Jubair, Nigel A J McMillan
The field of gene editing is undergoing unprecedented growth. The first ex vivo human clinical trial in China started in 2016, more than 1000 US patents have been filed, and there is exponential growth in publications. The ability to edit genes with high fidelity is promising for the development of new treatments for a range of diseases, particularly inherited conditions, infectious diseases, and cancers. For cancer, a major issue is the identification of driver mutations and oncogenes to target for therapeutic effect, and this requires the development of robust models with which to prove their efficacy...
September 15, 2017: Molecular Therapy. Nucleic Acids
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