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https://www.readbyqxmd.com/read/28812922/a-circulating-micro-rna-signature-serves-as-a-diagnostic-and-prognostic-indicator-in-sarcoidosis
#1
Christian Ascoli, Yue Huang, Cody Schott, Benjamin A Turturice, Ahmed Metwally, David L Perkins, Patricia W Finn
Micro-RNAs (miRNAs) act as post-transcriptional regulators of gene expression. In sarcoidosis, aberrant miRNA expression may enhance immune responses mounted against an unknown antigenic agent. We tested whether a distinct miRNA signature functions as a diagnostic biomarker and explored its role as an immune modulator in sarcoidosis. Expression of miRNAs from peripheral blood mononuclear cells from subjects that met clinical and histopathologic criteria for sarcoidosis were compared to those from matched controls in the ACCESS study...
August 16, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28812327/design-and-synthesis-of-terephthalic-acid-based-histone-deacetylase-inhibitors-with-dual-stage-anti-plasmodium-activity
#2
Katharina Stenzel, Ming Jang Chua, Sandra Duffy, Yevgeniya Antonova-Koch, Stephan Meister, Alexandra Hamacher, Matthias U Kassack, Elizabeth A Winzeler, Vicky M Avery, Thomas Kurz, Katherine T Andrews, Finn Kristian Hansen
In this work we aimed to develop parasite-selective HDAC inhibitors with activity against the disease-causing asexual blood stages of Plasmodium as well as causal prophylactic and/or transmission blocking properties. We report the design, synthesis and biological testing of a series of 13 terephthalic acid-based histone deacetylase inhibitors. All compounds showed low cytotoxicity against human embryonic kidney (HEK293) cells (IC50 8 - >51 µM), with 11 also having sub-micromolar in vitro activity against drug-sensitive (3D7) and multi-drug resistant (Dd2) asexual blood stage Plasmodium falciparum parasites (IC50 ~ 0...
August 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28811957/mapping-the-human-t-cell-repertoire-to-recurrent-driver-mutations-in-myd88-and-ezh2-in-lymphoma
#3
Julie S Nielsen, Andrew R Chang, Darin A Wick, Colin G Sedgwick, Zusheng Zong, Andrew J Mungall, Spencer D Martin, Natalie N Kinloch, Susann Ott-Langer, Zabrina L Brumme, Steven P Treon, Joseph M Connors, Randy D Gascoyne, John R Webb, Brian R Berry, Ryan D Morin, Nicol Macpherson, Brad H Nelson
Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88(L265P), EZH2(Y641F) , and EZH2(Y641N) . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811868/selaginella-bryopteris-aqueous-extract-improves-stability-and-function-of-cryopreserved-human-mesenchymal-stem-cells
#4
Abhishek Kumar Singh, Anubhuti Jha, Arindam Bit, Andrey P Kiassov, Albert A Rizvanov, Archit Ojha, Pooja Bhoi, Pradeep Kumar Patra, Awanish Kumar, Akalabya Bissoyi
The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811696/relationship-between-fetal-loss-and-serum-gonadal-hormones-level-in-experimental-antiphospholipid-syndrome-mouse
#5
Shanmugam Velayuthaprabhu, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Hidehiko Matsubayashi, Govindaraju Archunan
To investigate the effects of antiphospholipid antibodies on establishment of pregnancy and changes in hormones such as estradiol-17ß (E2) and progesterone (P) levels in circulation. Hence, mice were immunized with human β2-Glycoprotein I (β2GPI) and the effect of these antibodies on fetuses weight, placental obsrvation, Serum levels of P and E2 in pregnant mice, hematological were observed. Immunization of mice with human β2-GPI resulted in elevated levels of antiphospholipid antibodies. The experimentally induced antiphospholipid syndrome mouse showed higher rate of fetal resorption, low number of viable fetuses, and "placental abnormalities"...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28811655/a-tissue-engineered-blood-vessel-model-of-hutchinson-gilford-progeria-syndrome-using-human-ipsc-derived-smooth-muscle-cells
#6
Leigh Atchison, Haoyue Zhang, Kan Cao, George A Truskey
Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811641/joint-inflammation-related-citrullination-of-functional-arginines-in-extracellular-proteins
#7
Kalle H Sipilä, Vipin Ranga, Pekka Rappu, Markku Mali, Laura Pirilä, Ilona Heino, Johanna Jokinen, Jarmo Käpylä, Mark S Johnson, Jyrki Heino
We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811532/protein-expression-changes-caused-by-spaceflight-as-measured-for-18-russian-cosmonauts
#8
Irina M Larina, Andrew J Percy, Juncong Yang, Christoph H Borchers, Andrei M Nosovsky, Anatoli I Grigoriev, Evgeny N Nikolaev
The effects of spaceflight on human physiology is an increasingly studied field, yet the molecular mechanisms driving physiological changes remain unknown. With that in mind, this study was performed to obtain a deeper understanding of changes to the human proteome during space travel, by quantitating a panel of 125 proteins in the blood plasma of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station. The panel of labeled prototypic tryptic peptides from these proteins covered a concentration range of more than 5 orders of magnitude in human plasma...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811469/rgd-delivery-of-truncated-coagulase-to-tumor-vasculature-affords-local-thrombotic-activity-to-induce-infarction-of-tumors-in-mice
#9
Rana Jahanban-Esfahlan, Khaled Seidi, Hassan Monhemi, Amir Daei Farshchi Adli, Babak Minofar, Peyman Zare, Davoud Farajzadeh, Safar Farajnia, Ramezan Behzadi, Mehran Mesgari Abbasi, Nosratollah Zarghami, Tahereh Javaheri
Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and αvβ3 endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811304/selectin-catch-bonds-mechanotransduce-integrin-activation-and-neutrophil-arrest-on-inflamed-endothelium-under-shear-flow
#10
Vasilios A Morikis, Shannon Chase, Ted Wun, Elliot L Chaikof, John L Magnani, Scott I Simon
E-selectin extends from the plasma membrane of inflamed endothelium and serves to capture leukocytes from flowing blood via long-lived catch-bonds that support slow leukocyte rolling under shear stress. Its ligands are glycosylated with the tetrasaccharide sialyl Lewis(x) (sLe(x)), which contributes to bond affinity and specificity. E-selectin mediated rolling transmits signals into neutrophils that triggers activation of high-affinity β2-integrins necessary for transition to shear resistant adhesion and transendothelial migration...
August 15, 2017: Blood
https://www.readbyqxmd.com/read/28811296/a-novel-d2o-tracer-method-to-quantify-rna-turnover-as-a-biomarker-of-de-novo-ribosomal-biogenesis-in-vitro-in-animal-models-and-in-human-skeletal-muscle
#11
Matthew S Brook, Daniel J Wilkinson, W Kyle Mitchell, Jonathan L Lund, Bethan E Phillips, Nathaniel J Sweczyk, Heikki Kainulainen, Sanna Lensu, Lauren G Koch, Steve L Britton, Paul L Greenhaff, Kenneth Smith, Philip J Atherton
Current methods to quantify RNA dynamics are beset with limitations. Here, we developed a novel stable isotope (D2O)-methodology to quantify RNA synthesis (i.e. ribosomal biogenesis) in cells, animal models, and humans. Firstly, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes (±) 50ng.ml(-1) IGF-1. Secondly, rat quadriceps [untrained n=9; 7-wks interval-"like" training n=13] were collected after ~3-wks D2O (70-Atom%) administration, with body-water enrichment (BWE) monitored via blood sampling...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#12
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
August 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28810870/vector-borne-and-zoonotic-diseases-of-dogs-in-north-west-new-south-wales-and-the-northern-territory-australia
#13
Amanda J Shapiro, Graeme Brown, Jacqueline M Norris, Katrina L Bosward, Debbie J Marriot, Nandhakumar Balakrishnan, Edward B Breitschwerdt, Richard Malik
BACKGROUND: Vector-borne diseases of dogs in Australian Aboriginal communities are relatively unexplored. These dogs represent a unique group with variable ecto- and endo-parasitic burdens, nutritional stresses and a general lack of veterinary intervention. We investigated haemoprotozoal and bacterial pathogen prevalences in relation to erythrocyte and platelet numbers in dogs from North-West New South Wales (N-W NSW) and the Northern Territory (NT; Central Australia). METHODS: Real-time PCR (qPCR) amplification of Anaplasma platys, Babesia vogeli, Mycoplasma haemocanis, Candidatus Mycoplasma haematoparvum and Bartonella spp...
August 15, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28810865/cryptic-plasmodium-ovale-concurrent-with-mixed-plasmodium-falciparum-and-plasmodium-malariae-infection-in-two-children-from-central-african-republic
#14
Cynthia Bichara, Philippe Flahaut, Damien Costa, Anne-Lise Bienvenu, Stephane Picot, Gilles Gargala
BACKGROUND: Since several malaria parasite species are usually present in a particular area, co-infections with more than one species of Plasmodium are more likely to occur in humans infected in these areas. In many mixed infections, parasite densities of the cryptic species may be low and often not recognized in clinical practice. CASE PRESENTATION: Two children (3 and 6 years old) adopted recently from Central African Republic were admitted to hospital because of intermittent fever...
August 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28810863/multiple-essential-functions-of-plasmodium-falciparum-actin-1-during-malaria-blood-stage-development
#15
Sujaan Das, Leandro Lemgruber, Chwen L Tay, Jake Baum, Markus Meissner
BACKGROUND: The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated...
August 15, 2017: BMC Biology
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#16
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28810633/clinical-significance-of-5-and-6-carboxyfluorescein-diacetate-succinimidyl-ester-labeled-microspheres-for-detecting-endothelial-progenitor-cells-in-human-peripheral-blood
#17
Chaolin Qiu, Denghai Zhang, Yongbin Chi, Qing Chen, Limin Xu, Qiuhua Xie
The aims of the present study were to establish a single-platform flow cytometry method using 5-(and 6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled microspheres as the reference for determining endothelial progenitor cell (EPC) number and to evaluate the efficacy of this detection method. Single-platform flow cytometry was used to count cell numbers using CFSE-stained fluorescent microspheres as the internal reference and the EPC numbers in specimens using this novel method were compared with an in vitro clonogenic counting assay...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810565/alteration-of-th17-and-foxp3-regulatory-t-cells-in-patients-with-unexplained-recurrent-spontaneous-abortion-before-and-after-the-therapy-of-hcg-combined-with-immunoglobulin
#18
Jing Sha, Fumin Liu, Jingfang Zhai, Xiaoyun Liu, Qinglin Zhang, Bei Zhang
We conducted this study to investigate the effects of the combination therapy of human chorionic gonadotropin (hCG) plus immunoglobulin (IG) on the levels of T helper 17 (Th17) cells and Foxp3(+) regulatory T cells (Treg) in patients with unexplained recurrent spontaneous abortion (URSA). Twenty pregnant women with URSA underwent combination therapy of hCG plus IG. Flow cytometry was performed to measure the proportions of Th17 and Treg cells before and after treatment. RT-PCR and ELISA were applied to detect the concentrations of interleukin (IL)-17, IL-6, IL-10, and transforming growth factor (TGF)-β1 in the peripheral blood...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810561/cytotoxic-t-lymphocytes-promote-cytarabine-induced-acute-myeloid-leukemia-cell-apoptosis-via-inhibiting-bcl-2-expression
#19
Rui Deng, Fang-Yi Fan, Hai Yi, Li Fu, Yan Zeng, Yi Wang, Xiao-Juan Miao, Yan-Rong Shuai, Guang-Cui He, Yi Su
Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) in vitro and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3(+)CD8(+) CTLs through immune stimulation...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810516/lectin-from-inflorescences-of-ornamental-crop-alpinia-purpurata-acts-on-immune-cells-to-promote-th1-and-th17-responses-nitric-oxide-release-and-lymphocyte-activation
#20
Jéssica de Santana Brito, Gustavo Ramos Salles Ferreira, Emeline Klimczak, Liliya Gryshuk, Nataly Diniz de Lima Santos, Leydianne Leite de Siqueira Patriota, Leyllane Rafael Moreira, Ana Karine Araújo Soares, Bruno Rafael Barboza, Patrícia Maria Guedes Paiva, Daniela Maria do Amaral Ferraz Navarro, Virgínia Maria Barros de Lorena, Cristiane Moutinho Lagos de Melo, Marília Cavalcanti Coriolano, Thiago Henrique Napoleão
Alpinia purpurata is an ornamental crop known as a source of bioactive molecules. This is the first study to report isolation of a lectin (carbohydrate-binding protein) from A. purpurata inflorescences (ApuL). The immunomodulatory potential of ApuL was evaluated by investigating its effects on the production of cytokines and release of nitric oxide by human peripheral blood mononuclear cells (PBMCs). In addition, the differentiation and activation of lymphocytes treated with ApuL was evaluated by immunophenotyping assays...
August 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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