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https://www.readbyqxmd.com/read/28544786/mir-122-modification-enhances-the-therapeutic-efficacy-of-adipose-tissue-derived-mesenchymal-stem-cells-against-liver-fibrosis
#1
Guohua Lou, Ying Yang, Feifei Liu, Bingjue Ye, Zhi Chen, Min Zheng, Yanning Liu
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR-122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR-122 modification can improve the therapeutic efficacy of adipose tissue-derived MSCs in treating liver fibrosis. MiR-122-modified AMSCs (AMSC-122) were constructed through lentivirus-mediated transfer of pre-miR-122...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28535778/exosomes-from-mesenchymal-stem-cells-induce-the-conversion-of-hepatocytes-into-progenitor-oval-cells
#2
Hao-Hsiang Wu, Oscar K Lee
BACKGROUND: We previously reported that mesenchymal stem cells (MSCs) possess therapeutic effects in a murine model of carbon tetrachloride-induced acute liver failure. In the study, we observed that the majority of repopulated hepatocytes were of recipient origin and were adjacent to transplanted MSCs; only a low percentage of repopulated hepatocytes were from transplanted MSCs. The findings indicate that MSCs guided the formation of new hepatocytes. Exosomes are important messengers for paracrine signaling delivery...
May 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28524762/exosomes-promote-restoration-after-an-experimental-animal-model-of-intracerebral-hemorrhage
#3
Laura Otero-Ortega, Mari Carmen Gómez de Frutos, Fernando Laso-García, Berta Rodríguez-Frutos, Esperanza Medina-Gutiérrez, Juan Antonio López, Jesús Vázquez, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Exosomes are gaining importance because they show great promise in therapeutic applications for several diseases. Particularly in stroke, exosomes derived from mesenchymal stem cell (MSC) therapy work as paracrine effectors responsible for promoting neurovascular remodeling and functional recovery. Adult male rats were subjected to intracerebral hemorrhage (ICH) by intrastriatal injection of collagenase type IV; 24 h after surgery, MSC-derived exosomes were administered through the tail vein. The rats were euthanized at 7 or 28 days after treatment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28514744/characterization-of-mouse-serum-exosomal-small-rna-content-the-origins-and-their-roles-in-modulating-inflammatory-response
#4
Xin Zhou, Zinan Jiao, Juling Ji, Shuyuan Li, Xiaodi Huang, Xiaoshuang Lu, Heng Zhao, Jingwen Peng, Xinya Chen, Qiuhong Ji, Yuhua Ji
In the last decade, although studies on exosomal microRNAs (miRNAs) derived from serum and other body fluids have increased dramatically; the contents and biological significance of serum exosomes under normal conditions remain unclear. In the present study, we profiled the small RNA content of mouse serum exosomes (mSEs) using small RNAseq and found that fragments of transfer RNAs (tRNAs) and miRNAs were the two predominant exosomal RNA species, accounting for approximately 60% and 10% of mapped reads, respectively...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507071/characterization-of-the-protein-tyrosine-phosphatase-lmprl-1-secreted-by-leishmania-major-via-the-exosome-pathway
#5
Sabine Leitherer, Joachim Clos, Elisabeth M Liebler-Tenorio, Ulrike Schleicher, Christian Bogdan, Didier Soulat
Similar to other intracellular pathogens, Leishmania parasites are known to evade the antimicrobial effector functions of host immune cells. To date, however, only few virulence factors have been described for Leishmania (L.) major, one of the causative agents of cutaneous leishmaniasis. Here, we characterized the expression and function of a L. major phosphatase which we termed LmPRL-1. This enzyme shows a strong structural similarity to the human phosphatases of regenerating liver (PRL-1, -2, and -3) that are regulating the proliferation, differentiation and motility of cells...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28505322/exosomes-in-toxicology-relevance-to-chemical-exposure-and-pathogenesis-of-environmentally-linked-diseases
#6
Dilshan S Harischandra, Shivani Ghaisas, Dharmin Rokad, Anumantha G Kanthasamy
Chronic exposure to environmental toxins has been known to initiate or aggravate various neurological disorders, carcinomas and other adverse health effects. Uptake by naïve cells of pathogenic factors such as danger-associated molecules, mRNAs, miRNAs or aggregated proteins leads to disruption in cellular homeostasis further resulting in inflammation and disease propagation. While early research tended to focus solely on exosomal removal of unwanted cellular contents, more recent reports indicate that these nano-vesicles play an active role in intercellular signaling...
May 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28483695/augmented-liver-targeting-of-exosomes-by-surface-modification-with-cationized-pullulan
#7
Ryo Tamura, Shinji Uemoto, Yasuhiko Tabata
Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes...
May 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28475894/diurnal-oscillations-in-liver-mass-and-cell-size-accompany-ribosome-assembly-cycles
#8
Flore Sinturel, Alan Gerber, Daniel Mauvoisin, Jingkui Wang, David Gatfield, Jeremy J Stubblefield, Carla B Green, Frédéric Gachon, Ueli Schibler
The liver plays a pivotal role in metabolism and xenobiotic detoxification, processes that must be particularly efficient when animals are active and feed. A major question is how the liver adapts to these diurnal changes in physiology. Here, we show that, in mice, liver mass, hepatocyte size, and protein levels follow a daily rhythm, whose amplitude depends on both feeding-fasting and light-dark cycles. Correlative evidence suggests that the daily oscillation in global protein accumulation depends on a similar fluctuation in ribosome number...
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28469765/melatonin-treatment-enhances-therapeutic-effects-of-exosomes-against-acute-liver-ischemia-reperfusion-injury
#9
Cheuk-Kwan Sun, Chih-Hung Chen, Chia-Lo Chang, Hsin-Ju Chiang, Pei-Hsun Sung, Kuan-Hung Chen, Yi-Ling Chen, Sheng-Yi Chen, Gour-Shenq Kao, Hsueh-Wen Chang, Mel S Lee, Hon-Kan Yip
This study tests the hypothesis that combined melatonin and exogenic adipose mesenchymal stem cell (ADMSC)-derived exosome treatment offers superior protection against liver ischemia-reperfusion (LIR) injury compared to either alone. In vitro studies utilized a macrophage cell line (RAW) pretreated with lipopolysaccharide and hepatocytes pretreated with melatonin or exosomes before hypoxia treatment, while in vitro experiments involved analyses of liver specimens from male adult Sprague-Dawley rats (n = 50) equally categorized into sham controls (SC), LIR only, LIR-exosome (100 µg, 30 minute post-LIR), LIR-melatonin (20 mg/kg, 30 minute post-LIR and 50 mg/kg at 6 and 18 hours post-LIR), and LIR-exosome-melatonin groups...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28456398/effect-of-circulating-exosomes-from-transition-cows-on-madin-darby-bovine-kidney-cell-function
#10
M A Crookenden, C G Walker, H Peiris, Y Koh, F Almughlliq, K Vaswani, S Reed, A Heiser, J J Loor, J K Kay, S Meier, S S Donkin, A Murray, V S R Dukkipati, J R Roche, M D Mitchell
The greatest risk of metabolic and infectious disease in dairy cows is during the transition from pregnancy to lactating (i.e., the transition period). The objective of this experiment was to determine the effects of extracellular vesicles (microvesicles involved in cell-to-cell signaling) isolated from transition cows on target cell function. We previously identified differences in the protein profiles of exosomes isolated from cows divergent in metabolic health status. Therefore, we hypothesized that these exosomes would affect target tissues differently...
April 26, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28438662/never-let-it-go-stopping-key-mechanisms-underlying-metastasis-to-fight-pancreatic-cancer
#11
REVIEW
E Giovannetti, C L van der Borden, A E Frampton, A Ali, O Firuzi, G J Peters
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis...
April 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28437377/microrna-21-is-required-for-local-and-remote-ischemic-preconditioning-in-multiple-organ-protection-against-sepsis
#12
Ping Jia, Xiaoli Wu, Yan Dai, Jie Teng, Yi Fang, Jiachang Hu, Jianzhou Zou, Mingyu Liang, Xiaoqiang Ding
OBJECTIVE: Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent...
April 21, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28407805/revelation-of-mrnas-and-proteins-in-porcine-milk-exosomes-by-transcriptomic-and-proteomic-analysis
#13
Ting Chen, Qian-Yun Xi, Jia-Jie Sun, Rui-Song Ye, Xiao Cheng, Rui-Ping Sun, Song-Bo Wang, Gang Shu, Li-Na Wang, Xiao-Tong Zhu, Qing-Yan Jiang, Yong-Liang Zhang
BACKGROUND: Milk is a complex liquid that provides nutrition to newborns. Recent reports demonstrated that milk is enriched in maternal-derived exosomes that are involved in fetal physiological and pathological conditions by transmission of exosomal mRNAs, miRNAs and proteins. Until now, there is no such research relevant to exosomal mRNAs and proteins in porcine milk, therefore, we have attempted to investigate porcine milk exosomal mRNAs and proteins using RNA-sequencing and proteomic analysis...
April 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28401565/serum-and-exosomal-mir-122-and-mir-199a-as-a-biomarker-to-predict-therapeutic-efficacy-of-hepatitis-c-patients
#14
Xiaoyang Jiao, Zhicheng Fan, Huanzhu Chen, Ping He, Yazhen Li, Qiaoxin Zhang, Changwen Ke
AIM: MicroRNA (miRNA), which has been shown to correlate with liver functions, has been proposed as a new biomarker reflecting liver injury. The aim of the study was to investigate miRNA -122 (miR-122) and mir-RNA -199a (miR-199a) as a biomarker for predicting therapeutic efficacy in hepatitis C (HepC)patients. METHODS: 47 HepC 1b patients and 16 healthy subjects were enrolled in the study. Serum and exosomal mir-RNAs and other conventional biomarkers reflecting liver function were evaluated...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28395182/sensitive-luminescent-reporter-viruses-reveal-appreciable-release-of-hepatitis-c-virus-ns5a-protein-into-the-extracellular-environment
#15
Nicholas S Eyre, Amanda L Aloia, Michael A Joyce, Monrat Chulanetra, D Lorne Tyrrell, Michael R Beard
The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles...
April 7, 2017: Virology
https://www.readbyqxmd.com/read/28393839/exosome-delivered-egfr-regulates-liver-microenvironment-to-promote-gastric-cancer-liver-metastasis
#16
Haiyang Zhang, Ting Deng, Rui Liu, Ming Bai, Likun Zhou, Xia Wang, Shuang Li, Xinyi Wang, Haiou Yang, Jialu Li, Tao Ning, Dingzhi Huang, Hongli Li, Le Zhang, Guoguang Ying, Yi Ba
The metastatic organotropism has been one of the cancer's greatest mysteries since the 'seed and soil' hypothesis. Although the role of EGFR in cancer cells is well studied, the effects of secreted EGFR transported by exosomes are less understood. Here we show that EGFR in exosomes secreted from gastric cancer cells can be delivered into the liver and is integrated on the plasma membrane of liver stromal cells. The translocated EGFR is proved to effectively activate hepatocyte growth factor (HGF) by suppressing miR-26a/b expression...
April 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28382720/exosomes-derived-from-mir-181-5p-modified-adipose-derived-mesenchymal-stem-cells-prevent-liver-fibrosis-via-autophagy-activation
#17
Ying Qu, Qidi Zhang, Xiaobo Cai, Fei Li, Zhenzeng Ma, Mingyi Xu, Lungen Lu
Proliferating hepatic stellate cells (HSCs) respond to liver damage by secreting collagens that form fibrous scar tissue, which can lead to cirrhosis if in appropriately regulated. Advancement of microRNA (miRNA) hepatic therapies has been hampered by difficulties in delivering miRNA to damaged tissue. However, exosomes secreted by adipose-derived mesenchymal stem cells (ADSCs) can be exploited to deliver miRNAs to HSCs. ADSCs were engineered to overexpress miRNA-181-5p (miR-181-5p-ADSCs) to selectively home exosomes to mouse hepatic stellate (HST-T6) cells or a CCl4-induced liver fibrosis murine model and compared with non-targeting control Caenorhabditis elegans miR-67 (cel-miR-67)-ADSCs...
April 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28380368/brown-fat-derived-exosomes-small-vesicles-with-big-impact
#18
Yong Chen, Alexander Pfeifer
Adipose tissue (AT) not only stores energy, but also secretes hormones and releases small vesicles known as exosomes. Thomou et al. (2017) now show that exosomes secreted by brown fat carry miRNAs that regulate the liver. Thus, AT exosomes might have therapeutic and diagnostic relevance for metabolic disorders.
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28376502/circulating-exosomal-microrna-21-as-a-biomarker-in-each-tumor-stage-of-colorectal-cancer
#19
Mitsuo Tsukamoto, Hisae Iinuma, Takahiro Yagi, Keiji Matsuda, Yojiro Hashiguchi
OBJECTIVE: We clarified the predictive and prognostic value of circulating plasma exosomal microRNA-21 (miR-21) in each TNM stage of colorectal cancer (CRC) patients. METHODS: The microRNA (miRNA) profiles of the plasma exosomes, primary tumor tissues, and liver metastasis tissues from the same CRC patients were examined using a microarray. For validation analysis, the plasma exosome samples from 326 CRC patients were measured by TaqMan miRNA assays. RESULTS: In the miRNA microarray analyses, miR-21 showed the highest upregulation in exosomes, primary tumor tissues, and liver metastasis tissues...
April 5, 2017: Oncology
https://www.readbyqxmd.com/read/28366542/key-biological-processes-driving-metastatic-spread-of-pancreatic-cancer-as-identified-by-multi-omics-studies
#20
REVIEW
T Y S Le Large, M F Bijlsma, G Kazemier, H W M van Laarhoven, E Giovannetti, C R Jimenez
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood...
March 30, 2017: Seminars in Cancer Biology
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