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Journal of Translational Medicine

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https://www.readbyqxmd.com/read/28100276/realising-stratified-psychiatry-using-multidimensional-signatures-and-trajectories
#1
Dan W Joyce, Angie A Kehagia, Derek K Tracy, Jessica Proctor, Sukhwinder S Shergill
BACKGROUND: Stratified or personalised medicine targets treatments for groups of individuals with a disorder based on individual heterogeneity and shared factors that influence the likelihood of response. Psychiatry has traditionally defined diagnoses by constellations of co-occurring signs and symptoms that are assigned a categorical label (e.g. schizophrenia). Trial methodology in psychiatry has evaluated interventions targeted at these categorical entities, with diagnoses being equated to disorders...
January 18, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28088238/lymph-node-pooling-a-feasible-and-efficient-method-of-lymph-node-molecular-staging-in-colorectal-carcinoma
#2
Natalia Rakislova, Carla Montironi, Iban Aldecoa, Eva Fernandez, Josep Antoni Bombi, Mireya Jimeno, Francesc Balaguer, Maria Pellise, Antoni Castells, Miriam Cuatrecasas
BACKGROUND: Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. Nevertheless, the use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Our aim is to take a step forward in colon cancer (CC) lymph node (LN) pathology diagnosis by proposing a feasible and efficient molecular method in routine practice using reverse transcription loop-mediated isothermal amplification (RT-LAMP). RESULTS: Molecular detection of tumor cytokeratin 19 (CK19) mRNA with RT-LAMP was performed in 3206 LNs from 188 CC patients using two methods: individual analysis of 1449 LNs from 102 patients (individual cohort), and pooled LN analysis of 1757 LNs from 86 patients (pooling cohort)...
January 14, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#3
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28086962/inhibitory-effects-of-serum-from-sepsis-patients-on-epithelial-cell-migration-in-vitro-a-case-control-study
#4
Henna Jaurila, Vesa Koivukangas, Marjo Koskela, Fiia Gäddnäs, Sirpa Salo, Johanna Korvala, Maija Risteli, Toni Karhu, Karl-Heinz Herzig, Tuula Salo, Tero I Ala-Kokko
BACKGROUND: Sepsis delays wound re-epithelialization. In this study we explored the effect of human sepsis sera as well as the effects of cytokines, growth factors and exosomes of sepsis sera treated normal fibroblasts (NF) on keratinocyte migration and proliferation in vitro. METHODS: Serum samples were taken on days 1, 4, and 9 from 44 patients diagnosed with severe sepsis, and from 14 matching healthy controls. We evaluated the effects of sepsis serum with or without TNF-α, EGF, EGF receptor inhibitor or exosomes of sepsis sera treated NF on human keratinocyte (HaCaT) proliferation (BrdU assay), viability (MTT assay), and migration (horizontal wound healing model)...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28086815/antibiotics-induced-depletion-of-mice-microbiota-induces-changes-in-host-serotonin-biosynthesis-and-intestinal-motility
#5
Xiaolong Ge, Chao Ding, Wei Zhao, Lizhi Xu, Hongliang Tian, Jianfeng Gong, Minsheng Zhu, Jieshou Li, Ning Li
BACKGROUND: The gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism. METHODS: After 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28086811/study-of-the-microrna-expression-profile-of-foreskin-derived-mesenchymal-stromal-cells-following-inflammation-priming
#6
Hussein Fayyad-Kazan, Mohammad Fayyad-Kazan, Bassam Badran, Dominique Bron, Laurence Lagneaux, Mehdi Najar
BACKGROUND: Due to their self-renewal capacity, multi-lineage potential, and immunomodulatory properties, mesenchymal stromal cells (MSCs) are an attractive tool for different therapeutic strategies. Foreskin (FSK), considered as a biological waste material, has already been shown to be a valuable source of MSCs. Besides their typical fibroblast like morphology and International Society for cellular Therapy compliant phenotype, foreskin-MSCs (FSK-MSCs) are clonogenic, and highly proliferative cells with multi-lineage and strong immunomodulatory capacities...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28086781/effects-of-the-intradiscal-implantation-of-stromal-vascular-fraction-plus-platelet-rich-plasma-in-patients-with-degenerative-disc-disease
#7
Comella Kristin, Silbert Robert, Parlo Michelle
BACKGROUND: Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue and platelet rich plasma (PRP) can be obtained from peripheral blood. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF and PRP intra-discally into patients with degenerative disc disease. METHODS: A total of 15 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28057002/prediction-of-anti-inflammatory-proteins-peptides-an-insilico-approach
#8
Sudheer Gupta, Ashok K Sharma, Vibhuti Shastri, Midhun K Madhu, Vineet K Sharma
BACKGROUND: The current therapy for inflammatory and autoimmune disorders involves the use of nonspecific anti-inflammatory drugs and other immunosuppressant, which are often accompanied with potential side effects. As an alternative therapy, anti-inflammatory peptides are recently being exploited as anti-inflammatory agents for treatment of various inflammatory diseases such as Alzheimer's disease and rheumatoid arthritis. Thus, understanding the correlation between amino acid sequence and its potential anti-inflammatory property is of great importance for the discovery of novel and efficient anti-inflammatory peptide-based therapeutics...
January 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28057026/advances-in-rare-cell-isolation-an-optimization-and-evaluation-study
#9
Stefan Schreier, Piamsiri Sawaisorn, Rachanee Udomsangpetch, Wannapong Triampo
BACKGROUND: Rare nucleated CD45 negative cells in peripheral blood may be malignant such as circulating tumor cells. Untouched isolation thereof by depletion of normal is favored yet still technological challenging. We optimized and evaluated a novel magnetic bead-based negative selection approach for enhanced enrichment of rare peripheral blood nucleated CD45 negative cells and investigated the problem of rare cell contamination during phlebotomy. METHODS: Firstly, the performance of the magnetic cell separation system was assessed using leukocytes and cultivated fibroblast cells in regard to depletion efficiency and the loss of cells of interest...
January 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28052772/placental-mitochondrial-dna-and-cyp1a1-gene-methylation-as-molecular-signatures-for-tobacco-smoke-exposure-in-pregnant-women-and-the-relevance-for-birth-weight
#10
Bram G Janssen, Wilfried Gyselaers, Hyang-Min Byun, Harry A Roels, Ann Cuypers, Andrea A Baccarelli, Tim S Nawrot
BACKGROUND: Maternal smoking during pregnancy results in an increased risk of low birth weight through perturbations in the utero-placental exchange. Epigenetics and mitochondrial function in fetal tissues might be molecular signatures responsive to in utero tobacco smoke exposure. METHODS: In the framework of the ENVIRONAGE birth cohort, we investigated the effect of self-reported tobacco smoke exposure during pregnancy on birth weight and the relation with placental tissue markers such as, (1) relative mitochondrial DNA (mtDNA) content as determined by real-time quantitative PCR, (2) DNA methylation of specific loci of mtDNA (D-loop and MT-RNR1), and (3) DNA methylation of the biotransformation gene CYP1A1 (the last two determined by bisulfite-pyrosequencing)...
January 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049497/two-differentially-structured-collagen-scaffolds-for-potential-urinary-bladder-augmentation-proof-of-concept-study-in-a-g%C3%A3-ttingen-minipig-model
#11
Dorothea Leonhäuser, Katja Stollenwerk, Volker Seifarth, Isabella M Zraik, Michael Vogt, Pramod K Srinivasan, Rene H Tolba, Joachim O Grosse
BACKGROUND: The repair of urinary bladder tissue is a necessity for tissue loss due to cancer, trauma, or congenital abnormalities. Use of intestinal tissue is still the gold standard in the urological clinic, which leads to new problems and dysfunctions like mucus production, stone formation, and finally malignancies. Therefore, the use of artificial, biologically derived materials is a promising step towards the augmentation of this specialised tissue. The aim of this study was to investigate potential bladder wall repair by two collagen scaffold prototypes, OptiMaix 2D and 3D, naïve and seeded with autologous vesical cells, as potential bladder wall substitute material in a large animal model...
January 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049487/endothelial-microparticles-are-increased-in-congenital-heart-diseases-and-contribute-to-endothelial-dysfunction
#12
Ze-Bang Lin, Hong-Bo Ci, Yan Li, Tian-Pu Cheng, Dong-Hong Liu, Yan-Sheng Wang, Jun Xu, Hao-Xiang Yuan, Hua-Ming Li, Jing Chen, Li Zhou, Zhi-Ping Wang, Xi Zhang, Zhi-Jun Ou, Jing-Song Ou
BACKGROUND: We previously demonstrated that endothelial microparticles (EMPs) are increased in mitral valve diseases and impair valvular endothelial cell function. Perioperative systemic inflammation is an important risk factor and complication of cardiac surgery. In this study, we investigate whether EMPs increase in congenital heart diseases to promote inflammation and endothelial dysfunction. METHODS: The level of plasma EMPs in 20 patients with atrial septal defect (ASD), 23 patients with ventricular septal defect (VSD), and 30 healthy subjects were analyzed by flow cytometry...
January 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049494/adjuvant-effects-of-a-sequence-engineered-mrna-vaccine-translational-profiling-demonstrates-similar-human-and-murine-innate-response
#13
Darin K Edwards, Edith Jasny, Heesik Yoon, Nigel Horscroft, Brian Schanen, Tanya Geter, Mariola Fotin-Mleczek, Benjamin Petsch, Vaughan Wittman
BACKGROUND: Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. METHODS: In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model...
January 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049490/mobilization-of-hematopoietic-stem-cells-with-the-novel-cxcr4-antagonist-pol6326-balixafortide-in-healthy-volunteers-results-of-a-dose-escalation-trial
#14
Darja Karpova, Susanne Bräuninger, Eliza Wiercinska, Ariane Krämer, Belinda Stock, Jochen Graff, Hans Martin, Achim Wach, Christophe Escot, Garry Douglas, Barbara Romagnoli, Eric Chevalier, Klaus Dembowski, Leon Hooftman, Halvard Bonig
BACKGROUND: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF. METHODS: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1-2 h infusion of 500-2500 µg/kg of balixafortide...
January 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27998294/directed-differentiation-of-human-ipsc-into-insulin-producing-cells-is-improved-by-induced-expression-of-pdx1-and-nkx6-1-factors-in-ipc-progenitors
#15
Maciej P Walczak, Anna M Drozd, Ewelina Stoczynska-Fidelus, Piotr Rieske, Dawid P Grzela
BACKGROUND: Induced pluripotent stem cells (iPSC) possess an enormous potential as both, scientific and therapeutic tools. Their application in the regenerative medicine provides new treatment opportunities for numerous diseases, including type 1 diabetes. In this work we aimed to derive insulin producing cells (IPC) from iPS cells established in defined conditions. METHODS: We optimized iPSC generation protocol and created pluripotent cell lines with stably integrated PDX1 and NKX6...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27998282/does-therapeutic-hypothermia-during-extracorporeal-cardiopulmonary-resuscitation-preserve-cardiac-function
#16
Harald A Bergan, Per S Halvorsen, Helge Skulstad, Erik Fosse, Jan F Bugge
BACKGROUND: Extracorporeal cardiopulmonary resuscitation (E-CPR) is increasingly used as a rescue method in the management of cardiac arrest and provides the opportunity to rapidly induce therapeutic hypothermia. The survival after a cardiac arrest is related to post-arrest cardiac function, and the application of therapeutic hypothermia post-arrest is hypothesized to improve cardiac outcome. The present animal study compares normothermic and hypothermic E-CPR considering resuscitation success, post-arrest left ventricular function and magnitude of myocardial injury...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27998274/repressed-sirt1-pgc-1%C3%AE-pathway-and-mitochondrial-disintegration-in-ipsc-derived-rpe-disease-model-of-age-related-macular-degeneration
#17
Nady Golestaneh, Yi Chu, Shuk Kei Cheng, Hong Cao, Eugenia Poliakov, Daniel M Berinstein
BACKGROUND: Study of age related macular degeneration (AMD) has been hampered by lack of human models that represent the complexity of the disease. Here we have developed a human in vitro disease model of AMD to investigate the underlying AMD disease mechanisms. METHODS: Generation of iPSCs from retinal pigment epithelium (RPE) of AMD donors, age-matched normal donors, skin fibroblasts of a dry AMD patient, and differentiation of iPSCs into RPE (AMD RPE-iPSC-RPE, normal RPE-iPSC-RPE and AMD Skin-iPSC-RPE, respectively)...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27998273/lncrna-malat1-promotes-development-of-mantle-cell-lymphoma-by-associating-with-ezh2
#18
Xin Wang, Lalit Sehgal, Neeraj Jain, Tamer Khashab, Rohit Mathur, Felipe Samaniego
BACKGROUND: Mantle cell lymphoma (MCL) is considered an aggressive subtype of non-Hodgkin's lymphoma with variable treatment responses. There is an urgent need to identify novel markers with prognostic and therapeutic value for MCL. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancers, including MCL. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a lncRNA located at pathognomonic translocation site of t (11; 14) of MCL. MALAT1 is known to be overexpressed in solid tumors and hematologic malignancies...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27998272/association-of-mitochondrial-dna-variants-with-myalgic-encephalomyelitis-chronic-fatigue-syndrome-me-cfs-symptoms
#19
Maureen R Hanson, Zhenglong Gu, Alon Keinan, Kaixiong Ye, Arnaud Germain, Paul Billing-Ross
Earlier this year, we described an analysis of mitochondrial DNA (mtDNA) variants in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) patients and healthy controls. We reported that there was no significant association of haplogroups or singe nucleotide polymorphisms (SNPs) with disease status. Nevertheless, a commentary about our paper appeared (Finsterer and Zarrouk-Mahjoub. J Transl Med14:182, 2016) that criticized the association of mtDNA haplogroups with ME/CFS, a conclusion that was absent from our paper...
December 20, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27998269/increased-t-cell-breadth-and-antibody-response-elicited-in-prime-boost-regimen-by-viral-vector-encoded-homologous-siv-gag-env-in-outbred-cd1-mice
#20
Anne-Marie Carola Andersson, Peter Johannes Holst
BACKGROUND: A major obstacle for the development of HIV vaccines is the virus' worldwide sequence diversity. Nevertheless, the presence of T cell epitopes within conserved regions of the virus' structural Gag protein and conserved structures in the envelope (env) sequence raises the possibility that cross-reactive responses may be induced by vaccination. In this study, the aim was to investigate the importance of antigenic match on immunodominance and breadth of obtainable T cell responses...
December 20, 2016: Journal of Translational Medicine
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