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https://www.readbyqxmd.com/read/28224705/the-role-of-exosomes-in-hepatitis-liver-cirrhosis-and-hepatocellular-carcinoma
#1
REVIEW
Jiliang Shen, Chiung-Kuei Huang, Hong Yu, Bo Shen, Yaping Zhang, Yuelong Liang, Zheyong Li, Xu Feng, Jie Zhao, Lian Duan, Xiujun Cai
Exosomes are small vesicles that were initially thought to be a mechanism for discarding unneeded membrane proteins from reticulocytes. Their mediation of intercellular communication appears to be associated with several biological functions. Current studies have shown that most mammalian cells undergo the process of exosome formation and utilize exosome-mediated cell communication. Exosomes contain various microRNAs, mRNAs and proteins. They have been reported to mediate multiple functions, such as antigen presentation, immune escape and tumour progression...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28211508/mvp-mediated-exosomal-sorting-of-mir-193a-promotes-colon-cancer-progression
#2
Yun Teng, Yi Ren, Xin Hu, Jingyao Mu, Abhilash Samykutty, Xiaoying Zhuang, Zhongbin Deng, Anil Kumar, Lifeng Zhang, Michael L Merchant, Jun Yan, Donald M Miller, Huang-Ge Zhang
Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP)...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28211494/hepatocyte-secreted-extracellular-vesicles-modify-blood-metabolome-and-endothelial-function-by-an-arginase-dependent-mechanism
#3
Felix Royo, Laura Moreno, Justyna Mleczko, Laura Palomo, Esperanza Gonzalez, Diana Cabrera, Angel Cogolludo, Francisco Perez Vizcaino, Sebastiaan van-Liempd, Juan M Falcon-Perez
Hepatocytes release extracellular vesicles (EVs) loaded with signaling molecules and enzymes into the bloodstream. Although the importance of EVs in the intercellular communication is already recognized, the metabolic impact of the enzymes carried by these vesicles is still unclear. We evaluated the global effect of the enzymatic activities of EVs by performing untargeted metabolomic profiling of serum samples after their exposure to EVs. This approach revealed a significant change in the abundance of 94 serum metabolic signals...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208010/circulating-plasma-and-exosomal-micrornas-as-indicators-of-drug-induced-organ-injury-in-rodent-models
#4
Young-Eun Cho, Sang-Hyun Kim, Byung-Heon Lee, Moon-Chang Baek
This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28202367/exosomes-therapy-delivery-tools-and-biomarkers-of-diseases
#5
REVIEW
Lucio Barile, Giuseppe Vassalli
Virtually all cells in the organism secrete extracellular vesicles (EVs), a heterogeneous population of lipid bilayer membrane-enclosed vesicles that transport and deliver payloads of proteins and nucleic acids to recipient cells, thus playing central roles in cell-cell communications. Exosomes, nanosized EVs of endosomal origin, regulate many pathophysiological processes including immune responses and inflammation, tumour growth, and infection. Healthy subjects and patients with different diseases release exosomes with different RNA and protein contents into the circulation, which can be measured as biomarkers...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#6
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28160157/a-comparison-of-serum-mirnas-influencing-metastatic-growth-of-emt6-vs-4thm-tumor-cells-in-wild-type-and-cd200r1ko-mice
#7
Reginald M Gorczynski, Fang Zhu, Zhiqi Chen, Ohla Kos, Ismat Khatri
PURPOSE: We investigated whether miRNAs in exosomes from EMT6 or 4THM tumor-bearing mice played a role in regulating inflammatory cytokine expression and/or metastasis in WT mice injected with EMT6 and/or 4THM tumor cells. METHODS: EMT6 tumors in BALB/c CD200R1KO mice resolve following surgical resection of localized tumor and immunization with irradiated EMT6 cells along with CpG as adjuvant. Wild-type (WT) animals treated in the same fashion develop pulmonary and liver metastases within 20 days of surgery...
February 3, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28148795/hepatitis-b-virus-encoded-mirna-controls-viral-replication
#8
Xi Yang, Hongfeng Li, Huahui Sun, Hongxia Fan, Yaqi Hu, Min Liu, Xin Li, Hua Tang
: microRNAs (miRNAs) are a class of small single-stranded non-coding functional RNAs. Hepatitis B virus (HBV) is an enveloped DNA virus with virions and subviral forms of particles that lack a core. It was not known whether HBV encodes miRNAs. Here, we identified an HBV-encoded miRNA (called HBV-miR-3) by deep sequencing and northern blot. HBV-miR-3 is located at nts 373-393 of the HBV genome and was generated from 3.5Kb, 2,4Kb and 2.1Kb HBV in classic miRNA biogenesis (Drosha-Dicer dependent) manner...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28115012/exosomes-derived-from-human-menstrual-blood-derived-stem-cells-alleviate-fulminant-hepatic-failure
#9
Lu Chen, Bingyu Xiang, Xiaojun Wang, Charlie Xiang
BACKGROUND: Human menstrual blood-derived stem cells (MenSCs) are a novel source of MSCs that provide the advantage of being easy to collect and isolate. Exosomes contain some mRNAs and adhesion molecules that can potentially impact cellular and animal physiology. This study aimed to investigate the therapeutic potential of MenSC-derived exosomes (MenSC-Ex) on AML12 cells (in vitro) and D-GalN/LPS-induced FHF mice (in vivo). METHODS: Transmission electron microscopy and Western blot were used to identify MenSC-Ex...
January 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28089078/hucmsc-exosome-derived-gpx1-is-required-for-the-recovery-of-hepatic-oxidant-injury
#10
Yongmin Yan, Wenqian Jiang, Youwen Tan, Shengqiang Zou, Hongguang Zhang, Fei Mao, Aihua Gong, Hui Qian, Wenrong Xu
Exosomes are small biological membrane vesicles secreted by various cells, including mesenchymal stem cells (MSCs). We previously reported that MSC-derived exosomes (MSC-Ex) can elicit hepatoprotective effects against toxicant-induced injury. However, the success of MSC-Ex-based therapy for treatment of liver diseases and the underlying mechanisms have not been well characterized. We used human umbilical cord MSC-derived exosome (hucMSC-Ex) administrated by tail vein or oral gavage at different doses and, in engrafted liver mouse models, noted antioxidant and anti-apoptotic effects and rescue from liver failure...
January 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28077652/exosome-mediated-intercellular-communication-between-hepatitis-c-virus-infected-hepatocytes-and-hepatic-stellate-cells
#11
Pradip B Devhare, Reina Sasaki, Shubham Shrivastava, Adrian M Di Bisceglie, Ranjit Ray, Ratna B Ray
: Fibrogenic pathways in the liver are principally regulated by activation of hepatic stellate cells (HSC). Fibrosis is associated with chronic hepatitis C virus (HCV) infection, although the mechanism is poorly understood. HSC comprise the major population of the non-parenchymal cells in the liver. Since HCV does not replicate in HSC, we hypothesized that exosomes secreted from HCV-infected hepatocytes activate HSC. Primary or immortalized human hepatic stellate cells (LX2) were exposed to exosomes derived from HCV-infected hepatocytes (HCV-exo) and the expression of fibrosis related genes was examined...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28039962/association-of-ficolin-3-with-abdominal-aortic-aneurysm-presence-and-progression
#12
Carlos-Ernesto Fernandez-García, Elena Burillo, Jes S Lindholt, Diego Martinez-Lopez, Katrine Pilely, Carla Mazzeo, Jean-Baptiste Michel, Jesus Egido, Peter Garred, Luis M Blanco-Colio, Jose L Martin-Ventura
BACKGROUND: Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. OBJECTIVES: To define extrahepatic sources of ficolin-3 in AAA, and investigate the role of ficolin-3 as a biomarker of AAA presence and progression. METHODS: Microvesicles (exosomes and microparticles) were isolated from culture conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall)...
December 31, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28027586/targeting-the-mitochondrial-pyruvate-carrier-attenuates-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#13
Kyle S McCommis, Wesley T Hodges, Elizabeth M Brunt, ILKe Nalbantoglu, William G McDonald, Christopher Holley, Hideji Fujiwara, Jean E Schaffer, Jerry R Colca, Brian N Finck
: Diseases of the liver related to metabolic syndrome have emerged as the most common and undertreated hepatic ailments. The cause of nonalcoholic fatty liver disease (NAFLD) is the aberrant accumulation of lipid in hepatocytes, though the mechanisms whereby this leads to hepatocyte dysfunction, death, and hepatic fibrosis are still unclear. Insulin-sensitizing thiazolidinediones have shown efficacy in treating nonalcoholic steatohepatitis (NASH), but their widespread use is constrained by dose-limiting side effects thought to be due to activation of the peroxisome proliferator-activated receptor γ (PPARγ)...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27994623/towards-therapeutic-delivery-of-extracellular-vesicles-strategies-for-in-vivo-tracking-and-biodistribution-analysis
#14
REVIEW
Giuliana Di Rocco, Silvia Baldari, Gabriele Toietta
Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27987184/look-who-s-talking-the-crosstalk-between-oxidative-stress-and-autophagy-supports-exosomal-dependent-release-of-hcv-particles
#15
REVIEW
Regina Medvedev, Eberhard Hildt, Daniela Ploen
Autophagy is a highly conserved and regulated intracellular lysosomal degradation pathway that is essential for cell survival. Dysregulation has been linked to the development of various human diseases, including neurodegeneration and tumorigenesis, infection, and aging. Besides, many viruses hijack the autophagosomal pathway to support their life cycle. The hepatitis C virus (HCV), a major cause of chronic liver diseases worldwide, has been described to induce autophagy. The autophagosomal pathway can be further activated in response to elevated levels of reactive oxygen species (ROS)...
December 16, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27978773/a-longitudinal-assessment-of-mir-122-and-gldh-as-biomarkers-of-drug-induced-liver-injury-in-the-rat
#16
Petra Thulin, Robert J Hornby, Mariona Auli, Gunnar Nordahl, Daniel J Antoine, Philip Starkey Lewis, Christopher E Goldring, B Kevin Park, Neus Prats, Björn Glinghammar, Ina Schuppe-Koistinen
CONTEXT: There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies. OBJECTIVE: To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH)...
December 15, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27913196/nf-kb-regulated-exosomal-mir-155-promotes-the-inflammation-associated-with-arsenite-carcinogenesis
#17
Chao Chen, Fei Luo, Xinlu Liu, Lu Lu, Hui Xu, Qianlei Yang, Junchao Xue, Le Shi, Jun Li, Aihua Zhang, Qizhan Liu
In the cancer microenvironment, extracellular communication allows various types of cells to coordinate and execute biological functions. Emerging evidence indicates that exosomes, as mediators of cell communication, are involved in tumor progression. Little is known, however, about the mechanism by which exosomal miRNAs regulate inflammatory infiltration in arsenite-induced liver cancer. The present research aimed to determine if miRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 and THLE-3 cells, which are functionally active in the recipient cells...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27882696/fetuin-a-alpha-2hs-glycoprotein-modulates-growth-motility-invasion-and-senescence-in-high-grade-astrocytomas
#18
Gladys N Nangami, Amos M Sakwe, Michael G Izban, Tanu Rana, Philip E Lammers, Portia Thomas, Zhenbang Chen, Josiah Ochieng
Glioblastomas (high-grade astrocytomas) are highly aggressive brain tumors with poor prognosis and limited treatment options. In the present studies, we have defined the role of fetuin-A, a liver-derived multifunctional serum protein, in the growth of an established glioblastoma cell line, LN229. We hereby demonstrate that these cells synthesize ectopic fetuin-A which supports their growth in culture in the absence of serum. We have demonstrated that a panel of tissue microarray (TMA) of glioblastomas also express ectopic fetuin-A...
December 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27852847/visualizing-the-essential-role-of-complete-virion-assembly-machinery-in-efficient-hepatitis-c-virus-cell-to-cell-transmission-by-a-viral-infection-activated-split-intein-mediated-reporter-system
#19
Fanfan Zhao, Ting Zhao, Libin Deng, Dawei Lv, Xiaolong Zhang, Xiaoyu Pan, Jun Xu, Gang Long
: Hepatitis C virus (HCV) infects 2 to 3% of the world population and is a leading cause of liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. Many aspects of HCV study, ranging from molecular virology and antiviral drug development to drug resistance profiling, were supported by straightforward assays of HCV replication and infection. Among these assays, the HCV-dependent fluorescence relocalization (HDFR) system allowed live-cell visualization of infection without modifying the viral genome, but this strategy required careful recognition of the fluorescence relocalization pattern for its high fluorescence background in the cytoplasm...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27833848/neutral-ceramidase-enriched-exosomes-prevent-palmitic-acid-induced-insulin-resistance-in-h4iiec3-hepatocytes
#20
Qun Zhu, Rongping Zhu, Junfei Jin
Oversupply of free fatty acids such as palmitic acid (PA) from the portal vein may cause liver insulin resistance. Production of reactive oxygen species plays a pivotal role in PA-induced insulin resistance in H4IIEC3 hepatocytes. Recently, we found that exosomes secreted from INS-1 cells that were transfected with neutral ceramidase (NCDase) plasmids had raised NCDase activity; these NCDase-enriched exosomes could inhibit PA-induced INS-1 cell apoptosis. Here, we showed that PA reduced insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 2 and decreased insulin-stimulated uptake of the fluorescent glucose analog 2-NBDG, confirming that insulin resistance occurred in PA-treated H4IIEC3 cells...
November 2016: FEBS Open Bio
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