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https://www.readbyqxmd.com/read/29145157/bmscs-derived-mir-223-containing-exosomes-contribute-to-liver-protection-in-experimental-autoimmune-hepatitis
#1
Lu Chen, Feng-Bin Lu, Da-Zhi Chen, Jin-Lu Wu, En-de Hu, Lan-Man Xu, Ming-Hua Zheng, Hui Li, Yu Huang, Xiao-Ya Jin, Yue-Wen Gong, Zhuo Lin, Xiao-Dong Wang, Yong-Ping Chen
Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29138862/liver-kinase%C3%A2-b1-restoration-promotes-exosome-secretion-and-motility-of-lung-cancer-cells
#2
Cheng Zhang, Xiang Xiao, Minyi Chen, Hitham Aldharee, Yanfang Chen, Weiwen Long
Liver kinase B1 (LKB1) regulates a variety of cellular functions, including cell polarity, energy metabolism and cell growth, by targeting multiple signaling pathways such as AMPK/mTOR and p53. LKB1 functions as a tumor suppressor in sporadic cancers including lung cancer. Extracellular vesicles such as exosomes secreted by cancer cells modulate the tumor microenvironment and progression by targeting both tumor cells (autocrine actions) and other types of cells associated with tumors (paracrine actions). While the roles of LKB1 in cellular signaling in general is well-studied, its specific role in exosome-mediated signaling remains to be explored...
November 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29137633/bi-directional-exosome-driven-intercommunication-between-the-hepatic-niche-and-cancer-cells
#3
Nikolina Dioufa, Amanda M Clark, Bo Ma, Colin H Beckwitt, Alan Wells
BACKGROUND: Our understanding of the multiple roles exosomes play during tumor progression is still very poor and the contribution of the normal tissue derived exosomes in distant seeding and tumor outgrowth has also not been widely appreciated. METHODS: Using our all-human liver microphysiological system (MPS) platform as a model to closely recapitulate the early metastatic events, we isolated exosomes from both tumor cells and liver microenvironment. RESULTS: We observed that while priming of the hepatic niche (HepN) with MDA-231 breast cancer derived exosomes facilitated seeding of the cancer cells in the liver, subsequent tumor outgrowth was diminished; this was consistent with increased entry into dormancy...
November 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29122679/extracellular-vesicles-novel-mediator-for-cell-to-cell-communications-in-liver-pathogenesis
#4
REVIEW
Pradip B Devhare, Ratna B Ray
Extracellular vesicles (EVs) are membrane derived nanometer-sized vesicles. EVs are released by normal, diseased, and transformed cells in vitro and in vivo, and carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. Transferring biological information via EVs to neighboring cells and inter-cellular communication not only maintain physiological functions, but also involve in the pathogenesis of several diseases, including cancer. The aim of this review is to discuss the emerging role of EVs in viral hepatitis, non-alcoholic or alcoholic liver disease and liver cancers...
November 10, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29108252/circulating-exosomal-microrna-203-is-associated-with-metastasis-possibly-via-inducing-tumor-associated-macrophages-in-colorectal-cancer
#5
Yuki Takano, Takaaki Masuda, Hisae Iinuma, Rui Yamaguchi, Kuniaki Sato, Taro Tobo, Hidenari Hirata, Yosuke Kuroda, Sho Nambara, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Takahiro Ochiya, Katsuhiko Yanaga, Satoru Miyano, Koshi Mimori
A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis. Here, we identified miR-203 as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal miR-203, a major form in circulation, was associated with distant metastasis and an independent poor prognostic factor, whereas low expression in tumor tissues was a poor prognostic factor in CRC patients...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108215/-research-advances-in-the-role-of-mesenchymal-stem-cells-and-their-exosomes-in-treatment-of-liver-diseases
#6
W H Niu, J J Zhang, Z Y Zhu
At present, liver transplantation remains the most effective treatment for acute liver failure and advanced cirrhosis, but its use and promotion are limited by insufficient organ donors, financial consideration, and requirements for lifelong immunosuppression. In recent years, stem cell transplantation has been recommended as an effective substitutive therapy for liver disease. Mesenchymal stem cells, also known as pluripotent interstitial stromal cells, are self-renewing cells that can be found in almost all postnatal organs and tissues, including the liver...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29069781/downregulation-of-circulating-exosomal-mir-638-predicts-poor-prognosis-in-colon-cancer-patients
#7
Shushan Yan, Guangwang Dang, Xiaoyu Zhang, Chengwen Jin, Lang Qin, Yugang Wang, Min Shi, Haijin Huang, Quanhong Duan
Exosome-encapsulated microRNAs have been recognized as novel and stable biomarkers for cancer. However, little is known about the role of exosomal microRNAs in colon cancer. In the present study, we investigated the expression of serous exosomal microRNA-638 (miR-638) and its prognostic effect in patients with colon cancer. Serous exosomal samples were assayed by quantitative real-time PCR. Kaplan-Meier analysis was adopted to determine the overall survival (OS) and disease-free survival (DFS) of colon cancer patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063370/pathways-of-production-and-delivery-of-hepatocyte-exosomes
#8
Li Chen, Ruju Chen, Sherri Kemper, David R Brigstock
Hepatocyte exosomes (Exo(Hep)) are proposed to mediate physiological or pathophysiological signaling in a variety of hepatic target cells. Exo(Hep) were purified from the medium of primary mouse hepatocytes or AML12 cells and characterized as ~100 nm nanovesicles that were positive for proteins commonly found in exosomes (CD9, CD81, flotillin) or hepatocytes (asialoglycoprotein receptor). Ethanol treatment of hepatocytes caused increased Exo(Hep) release and increased cellular mRNA expression of components involved in intracellular vesicle trafficking (Rab 5a,b,c, Rab 7a, Rab 27a,b) or exosome biogenesis via the ESCRT (HGS, Alix, STAM1, TSG101, VTA1, YKT6) or ceramide (nSmase2) pathways...
October 23, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29029277/mir-122-release-in-exosomes-precedes-overt-tolvaptan-induced-necrosis-in-a-primary-human-hepatocyte-micropatterned-coculture-model
#9
Merrie Mosedale, J Scott Eaddy, O Joseph Trask, Natalie S Holman, Kristina K Wolf, Edward LeCluyse, Brenton R Ware, Salman R Khetani, Jingtao Lu, William J Brock, Sharin E Roth, Paul B Watkins
Idiosyncratic drug-induced liver injury (IDILI) is thought to often result from an adaptive immune attack on the liver. However, it has been proposed that the cascade of events culminating in an adaptive immune response begins with drug-induced hepatocyte stress, release of exosomal danger signals, and innate immune activation, all of which may occur in the absence of significant hepatocelluar death. A micropatterned coculture model (HepatoPac®) was used to explore the possibility that changes in exosome content precede overt necrosis in response to the IDILI drug tolvaptan...
September 28, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29023935/exosome-mir-335-as-a-novel-therapeutic-strategy-in-hepatocellular-carcinoma
#10
Fang Wang, Tian Hongwei, Ling Li, Klaus Piontek, Masazumi Sakaguchi, Florin M Selaru
Hepatocellular Cancer (HCC) is a common and deadly cancer. Most cases of HCC arise in a cirrhotic/fibrotic liver, raising the possibility that the environment plays a paramount role in cancer genesis. Previous studies from our group and others have shown that, in desmoplastic cancers, there is a rich intercellular communication between activated, cancer-associated fibroblasts (CAF) and cancer cells. Moreover, Extracellular Vesicles (EVs), or exosomes, were identified asan important arm of this intercellular communication platform...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28969005/pancreatic-cancer-derived-exosomes-promote-tumor-metastasis-and-liver-pre-metastatic-niche-formation
#11
Zeqian Yu, Susu Zhao, Long Ren, Lishan Wang, Zhangjun Chen, Robert M Hoffman, Jiahua Zhou
Exosomes play important roles in cell-cell communication, and are likely mediators of the metastatic cascade in cancer. This study examined the role of exosomes in pancreatic cancer cell adhesion, migration, and invasion. We isolated and purified exosomes from two isogenic pancreatic cancer cell lines with different metastatic potentials. Uptake of exosomes from highly metastatic Panc02-H7 cells decreased adhesion and increased migration and invasion capacity in weakly metastatic Panc02 cells in vitro. Exosomes from highly metastatic pancreatic cancer cells induced liver pre-metastatic niche formation in naïve mice and promoted primary tumor growth and liver metastasis in vivo...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28947960/exosome-encapsulated-micrornas-as-circulating-biomarkers-for-colorectal-cancer
#12
Shushan Yan, Bing Han, Shunyuan Gao, Xiaochen Wang, Zengfang Wang, Fakai Wang, Jianjun Zhang, Donghua Xu, Beicheng Sun
Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28934733/exosomes-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-liver-against-hepatic-ischemia-reperfusion-injury-via-activating-sphingosine-kinase-and-sphingosine-1-phosphate-signaling-pathway
#13
Yingdong Du, Dawei Li, Conghui Han, Haoyu Wu, Longmei Xu, Ming Zhang, Jianjun Zhang, Xiaosong Chen
BACKGROUND/AIMS: This study aimed to evaluate the effects of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury, as well as the underlying mechanisms. METHODS: Exosomes derived from hiPSC-MSCs were isolated and characterized both biochemically and biophysically. hiPSC-MSCs-Exo were injected systemically into a murine ischemia/reperfusion injury model via the inferior vena cava, and then the therapeutic effects were evaluated...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#14
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28895353/-circulating-long-noncoding-rnas-as-biomarkers-in-tumor-diagnosis
#15
Nan Jiang, Haihua Tian, Jinchang Pan, Zhaohui Gong
Long noncoding RNAs (lncRNAs) are involved in vital life processes of gene expression, epigenetic regulation and X-chromosome inactivation. lncRNAs are also closely associated with tumor initiation and progression. Moreover, lncRNAs may enter human circulation system in the form of microvesicle or exosome, or in combination with RNA binding protein. Interestingly, the circulating lncRNAs are widely existed in body fluids, such as blood and urine. We review the origin of circulating lncRNAs, and the detection methods as potential biomarkers...
June 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28814883/serum-exosomal-mir-125b-is-a-novel-prognostic-marker-for-hepatocellular-carcinoma
#16
Weifeng Liu, Jie Hu, Kaiqian Zhou, Feiyu Chen, Zheng Wang, Boyi Liao, Zhi Dai, Ya Cao, Jia Fan, Jian Zhou
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with high mortality. Circulating miRNA has been demonstrated as a novel noninvasive biomarker for many tumors. This study aimed to investigate the potential of circulating miR-125b as a prognostic marker of HCC. Exosomes were extracted from serum samples collected from two independent cohorts: cohort 1: HCC (n=30), chronic hepatitis B (CHB, n=30), liver cirrhosis (LC, n=30); cohort 2: HCC (n=128). We found that miR-125b levels were remarkably increased in exosomes compared to those in serum from patients with CHB, LC, and HCC (P<0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28807240/role-of-exosomes-in-treatment-of-hepatocellular-carcinoma
#17
REVIEW
Demetrios Moris, Eliza W Beal, Jeffery Chakedis, Richard A Burkhart, Carl Schmidt, Mary Dillhoff, Xufeng Zhang, Stamatios Theocharis, Timothy M Pawlik
Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28766848/microrna-30a-ameliorates-hepatic-fibrosis-by-inhibiting-beclin1-mediated-autophagy
#18
Jianliang Chen, Yue Yu, Shu Li, Yuting Liu, Shu Zhou, Shouji Cao, Jie Yin, Guoqiang Li
We explored the role of microRNA-30a (miR-30a) and the mechanism involved in hepatic fibrosis. MiR-30a overexpression was achieved by miR-30a mimics transfection in hepatic stellate cells (HSCs) (HSC-T6, LX-2), and miR-30a agomir (ago-miR-30a) treatment in mice. MiR-30a levels were measured using TaqMan miRNA assay system, and the localization of miR-30a was detected by fluorescence in situ hybridization (FISH). The interaction of miR-30a and Beclin1 was confirmed by dual-luciferase reporter assay. Autophagic flux was analysed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy and Western blot of LC3-II/I ratio...
August 1, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28749570/hepatocyte-derived-exosomes-promote-t-follicular-regulatory-cell-expansion-during-hcv-infection
#19
Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn
Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28740555/atg9b-deficiency-suppresses-autophagy-and-potentiates-endoplasmic-reticulum-stress-associated-hepatocyte-apoptosis-in-hepatocarcinogenesis
#20
Ning Wang, Hor-Yue Tan, Sha Li, Yibin Feng
The aim of this study was to investigate the mechanism underlying autophagy deficiency during hepatic carcinogenesis. For this purpose, we used choline-deficient, amino acid-defined (CDAA) hepatocarcinogenesis model in mice. miRNA microarrays combined with computational target predictions and GO analysis were used to identify molecular processes involved in carcinogenesis. PCR profiler array was employed to detect the dysregulated autophagy-related genes during carcinogenesis. We observed induction of hepatic tumours with increased inflammation, DNA damage, and cell death...
2017: Theranostics
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