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https://www.readbyqxmd.com/read/28335522/extracellular-vesicles-deliver-host-and-virus-rna-and-regulate-innate-immune-response
#1
REVIEW
Takahisa Kouwaki, Masaaki Okamoto, Hirotake Tsukamoto, Yoshimi Fukushima, Hiroyuki Oshiumi
The innate immune system plays a crucial role in controlling viral infection. Pattern recognition receptors (PRRs), such as Toll-like receptors and RIG-I-like receptors, sense viral components called pathogen-associated molecular patterns (PAMPs) and trigger signals to induce innate immune responses. Extracellular vesicles (EVs), including exosomes and microvesicles, deliver functional RNA and mediate intercellular communications. Recent studies have revealed that EVs released from virus-infected cells deliver viral RNA to dendritic cells and macrophages, thereby activating PRRs in recipient cells, which results in the expression of type I interferon and pro-inflammatory cytokines...
March 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334892/inhibition-of-homologous-phosphorolytic-ribonucleases-by-citrate-may-represent-an-evolutionarily-conserved-communicative-link-between-rna-degradation-and-central-metabolism
#2
Carlanne M Stone, Louise E Butt, Joshua C Bufton, Daniel C Lourenco, Darren M Gowers, Andrew R Pickford, Paul A Cox, Helen A Vincent, Anastasia J Callaghan
Ribonucleases play essential roles in all aspects of RNA metabolism, including the coordination of post-transcriptional gene regulation that allows organisms to respond to internal changes and environmental stimuli. However, as inherently destructive enzymes, their activity must be carefully controlled. Recent research exemplifies the repertoire of regulatory strategies employed by ribonucleases. The activity of the phosphorolytic exoribonuclease, polynucleotide phosphorylase (PNPase), has previously been shown to be modulated by the Krebs cycle metabolite citrate in Escherichia coli...
March 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28321122/the-emerging-roles-of-tumor-derived-exosomes-in-hematological-malignancies
#3
REVIEW
M Boyiadzis, T L Whiteside
Exosomes are small (30-150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. They have recently emerged as vehicles for intercellular transfer of molecular and genetic contents from parent to recipient cells. Exosome-mediated transfer of proteins or genes (RNA, miRNA, DNA) results in reprogramming of recipient cell functions. Exosomes carry and deliver information that is essential for health, and they participate in pathological events, including malignant transformation...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28290538/tlr-exosomes-exhibit-distinct-kinetics-and-effector-function
#4
Swetha Srinivasan, Michelle Su, Shashidhar Ravishankar, James Moore, PamelaSara Head, J Brandon Dixon, Fredrik Vannberg
The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. Here we show that exosomes from TLR stimulated cells can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28288106/the-rrp4-exosome-complex-recruits-and-channels-substrate-rna-by-a-unique-mechanism
#5
Milos A Cvetkovic, Jan Philip Wurm, Maxime J Audin, Stefan Schütz, Remco Sprangers
The exosome is a large molecular machine involved in RNA degradation and processing. Here we address how the trimeric Rrp4 cap enhances the activity of the archaeal enzyme complex. Using methyl-TROSY NMR methods we identified a 50-Å long RNA binding path on each Rrp4 protomer. We show that the Rrp4 cap can thus simultaneously recruit three substrates, one of which is degraded in the core while the others are positioned for subsequent degradation rounds. The local interaction energy between the substrate and the Rrp4-exosome increases from the periphery of the complex toward the active sites...
March 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28285404/exosomes-mediated-transfer-of-long-noncoding-rna-zfas1-promotes-gastric-cancer-progression
#6
Lei Pan, Wei Liang, Min Fu, Zhen-Hua Huang, Xia Li, Wen Zhang, Peng Zhang, Hui Qian, Peng-Cheng Jiang, Wen-Rong Xu, Xu Zhang
BACKGROUND: ZFAS1 is a newly identified long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes mediate cellular communications in cancer by transmitting active molecules. The presence of ZFAS1 in the circulating exosomes and the roles of exosomal ZFAS1 in gastric cancer (GC) remains unknown. The aim of this study was to investigate the potential roles of exosomal ZFAS1 in GC. METHODS: The expression of ZFAS1 was examined in the tumor tissues, serum samples, serum exosomes of GC patients and cell lines using qRT-PCR...
March 11, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28278290/exosomes-are-released-by-bystander-cells-exposed-to-radiation-induced-biophoton-signals-reconciling-the-mechanisms-mediating-the-bystander-effect
#7
Michelle Le, Cristian Fernandez-Palomo, Fiona E McNeill, Colin B Seymour, Andrew J Rainbow, Carmel E Mothersill
OBJECTIVE: The objective of our study was to explore a possible molecular mechanism by which ultraviolet (UV) biophotons could elicit bystander responses in reporter cells and resolve the problem of seemingly mutually exclusive mechanisms of a physical UV signal & a soluble factor-mediated bystander signal. METHODS: The human colon carcinoma cell line, HCT116 p53 +/+, was directly irradiated with 0.5 Gy tritium beta particles to induce ultraviolet biophoton emission...
2017: PloS One
https://www.readbyqxmd.com/read/28265569/functional-roles-and-therapeutic-applications-of-exosomes-in-hepatocellular-carcinoma
#8
REVIEW
Laura Santangelo, Cecilia Battistelli, Claudia Montaldo, Franca Citarella, Raffaele Strippoli, Carla Cicchini
Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA) from donor to recipient cells. Notably, tumor-derived exosomes (TDEs) appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC), the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28259747/exosome-based-immunomodulation-during-aging-a-nano-perspective-on-inflamm-aging
#9
REVIEW
Francesco Prattichizzo, Luigina Micolucci, Monica Cricca, Sabrina De Carolis, Emanuela Mensà, Antonio Ceriello, Antonio Domenico Procopio, Massimiliano Bonafè, Fabiola Olivieri
Exosomes are nanovesicles formed by inward budding of endosomal membranes. They exert complex immunomodulatory effects on target cells, acting both as antigen-presenting vesicles and as shuttles for packets of information like proteins, coding and non-coding RNA, and nuclear and mitochondrial DNA fragments. Albeit different, all such functions seem to be encompassed in the adaptive mechanism mediating the complex interactions of the organism with a variety of stressors, providing both for defense and for the evolution of symbiotic relationships with others organisms (gut microbiota, bacteria, and viruses)...
March 1, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28257521/exosome-secretion-affects-social-motility-in-trypanosoma-brucei
#10
Dror Eliaz, Sriram Kannan, Hadassa Shaked, Gil Arvatz, Itai Dov Tkacz, Lior Binder, Hiba Waldman Ben-Asher, Uthman Okalang, Vaibhav Chikne, Smadar Cohen-Chalamish, Shulamit Michaeli
Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28256706/analysis-of-extracellular-vesicles-produced-in-the-biofilm-by-the-dimorphic-yeast-pichia-fermentans
#11
Federica Leone, Lorenza Bellani, Simonetta Mucciflora, Lucia Giorgetti, Paolo Bongioanni, Marcella Simili, B E Maserti, Renata Del Carratore
The yeast Pichia fermentans DISAABA 726 strain (P. fermentans) is a dimorphic yeast that under different environmental conditions may switch from a yeast-like to pseudohyphal morphology. We hypothesize that exosomes-like vesicles (EV) could mediate this rapid modification. As EV are membrane-derived vesicles carrying lipids, proteins, mRNAs and microRNAs and have been recognized as important mediators of intercellular communication. Although it has been assumed for a long time that fungi release EV, knowledge of their functions is still limited...
March 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28255363/exosomes-derived-from-human-platelet-rich-plasma-prevent-apoptosis-induced-by-glucocorticoid-associated-endoplasmic-reticulum-stress-in-rat-osteonecrosis-of-the-femoral-head-via-the-akt-bad-bcl-2-signal-pathway
#12
Shi-Cong Tao, Ting Yuan, Bi-Yu Rui, Zhen-Zhong Zhu, Shang-Chun Guo, Chang-Qing Zhang
An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material...
2017: Theranostics
https://www.readbyqxmd.com/read/28252003/integrating-liquid-biopsies-into-the-management-of-cancer
#13
REVIEW
Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli
During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly...
March 2, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28247946/the-emerging-role-of-exosome-and-microvesicle-emv-based-cancer-therapeutics-and-immunotherapy
#14
REVIEW
Colin Moore, Uchini Kosgodage, Sigrun Lange, Jameel M Inal
There is an urgent need to develop new combination therapies beyond existing surgery, radio- and chemo-therapy, perhaps initially combining chemotherapy with the targeting specificities of immunotherapy. For this, strategies to limit inflammation and immuno-suppression and evasion in the tumour microenvironment are also needed. To devise effective new immunotherapies we must first understand tumour immunology, including the roles of T cells, macrophages, myeloid suppressor cells and of exosomes and microvesicles (EMVs) in promoting angiogenesis, tumour growth, drug resistance and metastasis...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28240774/early-detection-of-pancreatic-cancer-where-are-we-now-and-where-are-we-going
#15
REVIEW
Bin Zhou, Jian-Wei Xu, Yu-Gang Cheng, Jing-Yue Gao, San-Yuan Hu, Lei Wang, Han-Xiang Zhan
Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine, and saliva)...
February 27, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28239157/non-coding-rna-exosomal-micrornas-as-novel-adipokines
#16
Claire Greenhill
No abstract text is available yet for this article.
April 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28225755/intragenic-dna-methylation-prevents-spurious-transcription-initiation
#17
Francesco Neri, Stefania Rapelli, Anna Krepelova, Danny Incarnato, Caterina Parlato, Giulia Basile, Mara Maldotti, Francesca Anselmi, Salvatore Oliviero
In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that this Dnmt3b function is dependent on its enzymatic activity and recruitment to the gene body by H3K36me3...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28216464/exosomes-as-novel-bio-carriers-for-gene-and-drug-delivery
#18
REVIEW
Xin-Chi Jiang, Jian-Qing Gao
Clinical treatments have stalled in certain diseases due to a lack of proper therapeutic delivery systems. Recent studies have identified exosomes for their potential use as cell-free therapies, which may provide a novel mechanism for solving this problem. Exosomes are nanoscale extracellular vesicles that can transport rich cargos of proteins, lipids, DNA, and RNA. It is increasingly recognized that exosomes play a complex role in not only the physiological conditions but also pathological ones. Accumulating evidence suggests that exosomes are of paramount importance in distant cell-cell communication because they can enter the circulation when secreted and pass through additional biological barriers...
February 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#19
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213378/prognostic-role-of-circulating-exosomal-mirnas-in-multiple-myeloma
#20
Salomon Manier, Chia-Jen Liu, Hervé Avet-Loiseau, Jihye Park, Jiantao Shi, Federico Campigotto, Karma Z Salem, Daisy Huynh, Siobhan V Glavey, Bradley Rivotto, Antonio Sacco, Aldo M Roccaro, Juliette Bouyssou, Stéphane Minvielle, Philippe Moreau, Thierry Facon, Xavier Leleu, Edie Weller, Lorenzo Trippa, Irene M Ghobrial
Exosomes, secreted by several cell types, including cancer cells, can be isolated from the peripheral blood and have been shown to be powerful markers of disease progression in cancer. In this study, we examined the prognostic significance of circulating exosomal microRNAs (miRNAs) in multiple myeloma (MM). A cohort of 156 patients with newly diagnosed MM, uniformly treated and followed, was studied. Circulating exosomal miRNAs were isolated and used to perform small RNA sequencing analysis on 10 samples and a qRT-PCR array on 156 samples...
February 17, 2017: Blood
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