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https://www.readbyqxmd.com/read/28089078/hucmsc-exosome-derived-gpx1-is-required-for-the-recovery-of-hepatic-oxidant-injury
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27882696/fetuin-a-alpha-2hs-glycoprotein-modulates-growth-motility-invasion-and-senescence-in-high-grade-astrocytomas
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27810172/extracellular-vesicles-novel-mediators-of-cell-communication-in-metabolic-disease
#12
REVIEW
Isabel Huang-Doran, Chen-Yu Zhang, Antonio Vidal-Puig
Metabolic homeostasis emerges from the complex, multidirectional crosstalk between key metabolic tissues including adipose tissue, liver, and skeletal muscle. This crosstalk, traditionally mediated by hormones and metabolites, becomes dysregulated in human diseases such as obesity and diabetes. Extracellular vesicles (EVs; including exosomes) are circulating, cell-derived nanoparticles containing proteins and nucleic acids that interact with and modify local and distant cellular targets. Accumulating evidence, reviewed herein, supports a role for extracellular vesicles in obesity-associated metabolic disturbance, particularly the local and systemic inflammation characteristic of adipose and hepatic stress...
January 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27771257/excretory-secretory-products-in-the-echinococcus-granulosus-metacestode-is-the-intermediate-host-complacent-with-infection-caused-by-the-larval-form-of-the-parasite
#13
Guilherme B Dos Santos, Karina M Monteiro, Edileuza Danieli da Silva, Maria Eduarda Battistella, Henrique B Ferreira, Arnaldo Zaha
The genus Echinococcus consists of parasites that have a life cycle with two mammalian hosts. Their larval stage, called the hydatid cyst, develops predominantly in the liver and lungs of intermediate hosts. The hydatid cyst is the causative agent of cystic hydatid disease and the species Echinococcus granulosus, G1 haplotype, is responsible for the vast majority of cases in humans, cattle and sheep. Protein characterization in hydatid cysts is essential for better understanding of the host-parasite relationship and the fertility process of Echinococcus...
December 2016: International Journal for Parasitology
https://www.readbyqxmd.com/read/27760789/the-biodistribution-and-immune-suppressive-effects-of-breast-cancer-derived-exosomes
#14
Shu Wen Wen, Jaclyn Sceneay, Luize Goncalves Lima, Christina S F Wong, Melanie Becker, Sophie Krumeich, Richard J Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S Parker, Andreas Möller
Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45(+) bone marrow-derived cells...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27734397/cellular-or-exosomal-micrornas-associated-with-ccn-gene-expression-in-liver-fibrosis
#15
Li Chen, David R Brigstock
Liver fibrosis occurs during chronic injury and represents, in large part, an exaggerated matrigenic output by hepatic stellate cells (HSCs) which become activated as a result of injury-induced signaling pathways in parenchymal and inflammatory cells (hepatocytes, macrophages, etc.). The molecular components in these pathways (e.g., CCN proteins) are modulated by transcription factors as well as by factors such as microRNAs (miRs) that act posttranscriptionally. MiRs are small (~23 nt) noncoding RNAs that regulate gene expression by specifically interacting with the 3' untranslated region (UTR) of target gene mRNA to repress translation or enhance mRNA cleavage...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27720897/cell-type-specific-and-common-characteristics-of-exosomes-derived-from-mouse-cell-lines-yield-physicochemical-properties-and-pharmacokinetics
#16
Chonlada Charoenviriyakul, Yuki Takahashi, Masaki Morishita, Akihiro Matsumoto, Makiya Nishikawa, Yoshinobu Takakura
Exosomes are small membrane vesicles secreted from cells and are expected to be used as drug delivery systems. Important characteristics of exosomes, such as yield, physicochemical properties, and pharmacokinetics, may be different among different cell types. However, there is limited information about the effect of cell type on these characteristics. In the present study, we evaluated these characteristics of exosomes derived from five different types of mouse cell lines: B16BL6 murine melanoma cells, C2C12 murine myoblast cells, NIH3T3 murine fibroblasts cells, MAEC murine aortic endothelial cells, and RAW264...
January 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27716356/exosomes-derived-from-hcc-cells-induce-sorafenib-resistance-in-hepatocellular-carcinoma-both-in-vivo-and-in-vitro
#17
Zhen Qu, Junhua Wu, Junyi Wu, Dongjun Luo, Chunping Jiang, Yitao Ding
BACKGROUND: Exosomes are carriers of intercellular information and regulate the tumor microenvironment. They play an important role in drug resistance by transporting RNA molecules and proteins. However, their effects on sorafenib resistance in hepatocellular carcinoma (HCC) are not completely understood. METHODS: Exosomes were isolated from two invasive hepatoma cell lines (MHCC-97 L and MHCC-97H), and their roles in regulating sorafenib resistance in liver cancer cells as well as the underlying molecular mechanisms were determined...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27713136/the-role-of-extracellular-vesicles-in-mediating-progression-metastasis-and-potential-treatment-of-hepatocellular-carcinoma
#18
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27695899/sequential-cleavage-of-insulin-receptor-by-calpain-2-and-%C3%AE-secretase-impairs-insulin-signalling
#19
Tomoyuki Yuasa, Kikuko Amo-Shiinoki, Shuhei Ishikura, Mitsuyoshi Takahara, Takaaki Matsuoka, Hideaki Kaneto, Akio Kuroda, Munehide Matsuhisa, Seiichi Hashida
AIMS/HYPOTHESIS: Soluble insulin receptor (sIR), the ectodomain of the insulin receptor (IR), has been detected in human plasma and its concentration paralleled that of blood glucose. We have previously developed an in vitro model using HepG2 liver-derived cells, which mimics changes in sIR levels in plasma from diabetic patients and shows that calcium-dependent proteases cleave IR extracellularly (a process known as shedding). The present study aimed to reveal the mechanisms of IR cleavage...
September 30, 2016: Diabetologia
https://www.readbyqxmd.com/read/27666412/colorectal-cancer-cell-derived-microrna200-modulates-the-resistance-of-adjacent-blood-endothelial-barriers-in%C3%A2-vitro
#20
Silvio Holzner, Daniel Senfter, Serena Stadler, Anna Staribacher, Chi Huu Nguyen, Anna Gaggl, Silvana Geleff, Nicole Huttary, Sigurd Krieger, Walter Jäger, Helmut Dolznig, Robert M Mader, Georg Krupitza
Since cancer cells, when grown as spheroids, display drug sensitivity and radiation resistance patterns such as seen in vivo we recently established a three‑dimensional (3D) in vitro model recapitulating colorectal cancer (CRC)-triggered lymphatic endothelial cell (LEC)‑barrier breaching to study mechanisms of intra‑/extravasation. CRC metastasizes not only through lymphatics but also through blood vessels and here we extend the 3D model to the interaction of blood endothelial cells (BECs) with naïve and 5‑fluorouracil (5‑FU)‑resistant CRC CCL227 cells...
November 2016: Oncology Reports
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