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https://www.readbyqxmd.com/read/28107450/systemic-t-cells-immunosuppression-of-glioma-stem-cell-derived-exosomes-is-mediated-by-monocytic-myeloid-derived-suppressor-cells
#1
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28105773/exosomal-biomarkers-of-brain-insulin-resistance-associated-with-regional-atrophy-in-alzheimer-s-disease
#2
Roger J Mullins, Maja Mustapic, Edward J Goetzl, Dimitrios Kapogiannis
: Brain insulin resistance (IR), which depends on insulin-receptor-substrate-1 (IRS-1) phosphorylation, is characteristic of Alzheimer's disease (AD). Previously, we demonstrated higher pSer312-IRS-1 (ineffective insulin signaling) and lower p-panTyr-IRS-1 (effective insulin signaling) in neural origin-enriched plasma exosomes of AD patients vs. CONTROLS: Here, we hypothesized that these exosomal biomarkers associate with brain atrophy in AD. We studied 24 subjects with biomarker-supported probable AD (low CSF Aβ42 )...
January 20, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28104913/exosome-derived-micrornas-in-cancer-metabolism-possible-implications-in-cancer-diagnostics-and-therapy
#3
REVIEW
Marco Tomasetti, Wan Lee, Lory Santarelli, Jiri Neuzil
Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104773/exosomes-generated-from-ipsc-derivatives-new-direction-for-stem-cell-therapy-in-human-heart-diseases
#4
REVIEW
Ji-Hye Jung, Xuebin Fu, Phillip C Yang
Cardiovascular disease (CVD) is the leading cause of death in modern society. The adult heart innately lacks the capacity to repair and regenerate the damaged myocardium from ischemic injury. Limited understanding of cardiac tissue repair process hampers the development of effective therapeutic solutions to treat CVD such as ischemic cardiomyopathy. In recent years, rapid emergence of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes presents a valuable opportunity to replenish the functional cells to the heart...
January 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28104621/high-prevalence-of-mutant-kras-in-circulating-exosome-derived-dna-from-early-stage-pancreatic-cancer-patients
#5
K Allenson, J Castillo, F A San Lucas, G Scelo, D U Kim, V Bernard, G Davis, T Kumar, M Katz, M J Overman, L Foretova, E Fabianova, I Holcatova, V Janout, F Meric-Bernstam, P Gascoyne, I Wistuba, G Varadhachary, P Brennan, S Hanash, D Li, A Maitra, H Alvarez
BACKGROUND: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR (ddPCR) was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28104608/prothrombin-loading-of-vascular-smooth-muscle-cell-derived-exosomes-regulates-coagulation-and-calcification
#6
Alexander N Kapustin, Michael Schoppet, Leon J Schurgers, Joanne L Reynolds, Rosamund McNair, Alexander Heiss, Willi Jahnen-Dechent, Tilman M Hackeng, Georg Schlieper, Paul Harrison, Catherine M Shanahan
OBJECTIVE: The drug warfarin blocks carboxylation of vitamin K-dependent proteins and acts as an anticoagulant and an accelerant of vascular calcification. The calcification inhibitor MGP (matrix Gla [carboxyglutamic acid] protein), produced by vascular smooth muscle cells (VSMCs), is a key target of warfarin action in promoting calcification; however, it remains unclear whether proteins in the coagulation cascade also play a role in calcification. APPROACH AND RESULTS: Vascular calcification is initiated by exosomes, and proteomic analysis revealed that VSMC exosomes are loaded with Gla-containing coagulation factors: IX and X, PT (prothrombin), and proteins C and S...
January 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28103990/-effects-of-human-amniotic-epithelial-stem-cells-derived-exosomes-on-healing-of-wound-with-full-thickness-skin-defect-in-rats
#7
B Zhao, G F Wu, Y J Zhang, W Zhang, F F Yang, D Xiao, K X Zeng, J H Shi, L L Su, D H Hu
Objective: To investigate the effects of human amniotic epithelial stem cells-derived exosomes on healing of wound with full-thickness skin defect in rats. Methods: (1) Human amniotic epithelial stem cells were isolated from the amnion tissue of 5 full-term pregnant women in Department of Obstetrics of our hospital by the method of trypsin digestion, and their morphology was observed. The third passage of cells were stained with rhodamine-phalloidin for cytoskeleton observation. The third passage of cells were identified with flow cytometry through the detection of expressions of cell surface markers CD29, CD31, CD34, CD90, CD105, SSEA3, SSEA4 and immunity-related marker human leukocyte antigen-D related site (HLA-DR)...
January 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28103989/-experimental-research-on-the-effects-of-different-activators-on-the-formation-of-platelet-rich-gel-and-the-release-of-bioactive-substances-in-human-platelet-rich-plasma
#8
Y Yang, W Zhang, B Cheng
Objective: To explore the effects of calcium gluconate and thrombin on the formation of platelet-rich gel (PRG) and the release of bioactive substances in human platelet-rich plasma (PRP) and the clinical significance. Methods: Six healthy blood donors who met the inclusion criteria were recruited in our unit from May to August in 2016. Platelet samples of each donor were collected for preparation of PRP. (1) PRP in the volume of 10 mL was collected from each donor and divided into thrombin activation group (TA, added with 0...
January 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28102751/extracellular-vesicles-from-activated-platelets-a-semiquantitative-cryo-electron-microscopy-and-immuno-gold-labeling-study
#9
Alain R Brisson, Sisareuth Tan, Romain Linares, Céline Gounou, Nicolas Arraud
Cells release membrane vesicles in their surrounding medium either constitutively or in response to activating signals. Two main types of extracellular vesicles (EVs) are commonly distinguished based on their mechanism of formation, membrane composition and size. According to the current model, EVs shed from the plasma membrane, often called microvesicles, expose phosphatidylserine (PS) and range in size from 100 nm to 1 µm, while EVs originating from endosomal multi-vesicular bodies, called exosomes, contain tetraspanin proteins, including CD63, and range in size from 50 to 100 nm...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#10
Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28101763/mir-126-affects-brain-heart-interaction-after-cerebral-ischemic-stroke
#11
Jieli Chen, Chengcheng Cui, Xiaoping Yang, Jiang Xu, Poornima Venkat, Alex Zacharek, Peng Yu, Michael Chopp
Cardiovascular diseases are approximately three times higher in patients with neurological deficits than in patients without neurological deficits. MicroRNA-126 (MiR-126) facilitates vascular remodeling and decreases fibrosis and is emerging as an important factor in the pathogenesis of cardiovascular diseases and cerebral stroke. In this study, we tested the hypothesis that decreased miR-126 after ischemic stroke may play an important role in regulating cardiac function. Wild-type (WT), specific conditional-knockout endothelial cell miR-126 (miR-126(EC-/-)), and miR-126 knockout control (miR-126(fl/fl)) mice were subjected to distal middle cerebral artery occlusion (dMCAo) (n = 10/group)...
January 19, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28101591/functions-of-cancer-derived-extracellular-vesicles-in-immunosuppression
#12
REVIEW
Liliana Czernek, Markus Düchler
Extracellular vesicles, including exosomes, constitute an important element of intercellular communication by carrying a variety of molecules from producer to target cells. The transport of mRNA and miRNA can directly modulate gene expression in the target cells. The miRNA content in exosomes is characteristic for the cell from which the vesicles were derived enabling the usage of exosomes as biomarkers for the diagnosis various diseases, including cancer. Cancer-derived exosomes support the survival and progression of tumors in many ways and also contribute to the neutralization of the anti-cancer immune response...
January 18, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#13
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28098821/tumor-microenvironment-modulation-via-gold-nanoparticles-targeting-malicious-exosomes-implications-for-cancer-diagnostics-and-therapy
#14
REVIEW
Catarina Roma-Rodrigues, Luís R Raposo, Rita Cabral, Fabiana Paradinha, Pedro V Baptista, Alexandra R Fernandes
Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development...
January 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098260/hepatitis-b-virus-x-protein-is-capable-of-down-regulating-protein-level-of-host-antiviral-protein-apobec3g
#15
Ruidong Chen, Xue Zhao, Yongxiang Wang, Youhua Xie, Jing Liu
The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family proteins bind RNA and single-stranded DNA, and create C-to-U base modifications through cytidine deaminase activity. APOBEC3G restricts human immunodeficiency virus 1 (HIV-1) infection by creating hypermutations in proviral DNA, while HIV-1-encoded vif protein antagonizes such restriction by targeting APOBEC3G for degradation. APOBEC3G also inhibits hepatitis B virus (HBV): APOBEC3G co-expression inhibits HBV replication and evidences exist indicating APOBEC3G-mediated HBV hypermutations in patients...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#16
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096299/exosomes-from-eosinophils-autoregulate-and-promote-eosinophil-functions
#17
José Antonio Cañas, Beatriz Sastre, Carla Mazzeo, Mar Fernández-Nieto, José Manuel Rodrigo-Muñoz, Andrés González-Guerra, Manuel Izquierdo, Pilar Barranco, Santiago Quirce, Joaquín Sastre, Victoria Del Pozo
Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096131/nutrition-micrornas-and-human-health
#18
REVIEW
Juan Cui, Beiyan Zhou, Sharon A Ross, Janos Zempleni
MicroRNAs (miRs) hybridize with complementary sequences in mRNA and silence genes by destabilizing mRNA or preventing translation of mRNA. Over 60% of human protein-coding genes are regulated by miRs, and 1881 high-confidence miRs are encoded in the human genome. Evidence suggests that miRs not only are synthesized endogenously, but also might be obtained from dietary sources, and that food compounds alter the expression of endogenous miR genes. The main food matrices for studies of biological activity of dietary miRs include plant foods and cow milk...
January 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28095652/exosomal-trafficking-in-xenopus-development
#19
REVIEW
Michael Danilchik, Tess Tumarkin
Exosomes are small extracellular vesicles (EVs) secreted by many cell types in both normal and pathogenic circumstances. Because EVs, particularly exosomes, are known to transfer biologically active proteins, RNAs and lipids between cells, they have recently become the focus of intense interest as potential mediators of cell-cell communication, particularly in long-range and juxtacrine signaling events associated with adaptive immune function and progression of cancer. Among the EVs, exosomes appear particularly adapted for long-range delivery of cargoes between cells...
January 17, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28094758/exosomes-isolated-from-serum-of-systemic-sclerosis-patients-display-alterations-in-their-content-of-profibrotic-and-antifibrotic-microrna-and-induce-a-profibrotic-phenotype-in-cultured-normal-dermal-fibroblasts
#20
Peter J Wermuth, Piera-Velazquez Sonsoles, Sergio A Jimenez
OBJECTIVES: Exosomes are lipid bilayer-bound microvesicles containing various macromolecules including numerous microRNA (miRNA). Exosomes mediate intercellular communication by fusing and releasing their macromolecular content into target cells. Here, we analysed the content of profibrotic and antifibrotic miRNAs in exosomes isolated from the serum of systemic sclerosis (SSc) patients and tested their ability to induce a profibrotic phenotype in normal human dermal fibroblasts in vitro...
January 13, 2017: Clinical and Experimental Rheumatology
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