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miRNA liver

S M Plummer, J Wright, R A Currie
An increased incidence of liver tumours in the long term rodent bioassay is not an uncommon finding, invariably as a result of a non-genotoxic mode of action. Non-genotoxic liver carcinogenesis has been found to involve activation of certain nuclear hormone receptors (NHR) including the constitutive androstane receptor (CAR), peroxisome proliferator activated receptor alpha (PPARalpha) and arylhydrocarbon receptor (AHR) and more recently the induction of specific microRNAs (miRs), has also been demonstrated following CAR activation in studies up to 90 days (Koufaris et al...
2018: Toxicology Reports
Yuhong Li, Qi Ren, Lingyan Zhu, Yingshu Li, Jinfeng Li, Yiyang Zhang, Guoying Zheng, Tiesheng Han, Shufeng Sun, Fumin Feng
BACKGROUND: This investigation aimed to evaluate the role of methylation in the regulation of microRNA (miR)-122, miR-125b and miR-106b gene expression and the expression of their target genes during isoniazid (INH)-induced liver injury. METHODS: Rats were given INH 50 mg kg- 1 ·d- 1 once per day for 3, 7, 10, 14, 21 and 28 days and were sacrificed. Samples of blood and liver were obtained. RESULTS: We analysed the methylation and expression levels of miR-122, miR-125b and miR-106b and their potential gene targets in livers...
March 20, 2018: BMC Pharmacology & Toxicology
Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan
The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis...
March 19, 2018: PLoS Pathogens
Jing-Wen Bao, Jun Qiang, Yi-Fan Tao, Hong-Xia Li, Jie He, Pao Xu, De-Ju Chen
We investigated the effects of heat stress on genetically improved farmed tilapia, focusing on metabolic and immune responses. Differences in blood parameters, serum biochemistry, muscle fatty acid composition, and microRNA (miRNA) expression were analyzed in fish under heat stress. Fish were exposed to heat stress at 35 °C and sampled at 0, 6, 12, 24, and 48 h after exposure and compared with a control group maintained at 28 °C. The results showed that red and white blood cell counts, hemoglobin levels, and hematocrit values tended to increase (P < 0...
April 2018: Journal of Thermal Biology
Rikki A M Brown, Michael R Epis, Jessica L Horsham, Tasnuva D Kabir, Kirsty L Richardson, Peter J Leedman
BACKGROUND: microRNAs (miRNAs) are short non-coding RNAs that fine-tune gene expression. The aberrant expression of miRNAs is associated with many diseases and they have both therapeutic and biomarker potential. However, our understanding of their usefulness is dependent on the tools we have to study them. Previous studies have identified the need to optimise and standardise RNA extraction methods in order to avoid biased results. Herein, we extracted RNA from murine lung, liver and brain tissues using five commercially available total RNA extraction methods...
March 16, 2018: BMC Biotechnology
Aloma L D'Souza, John R Chevillet, Pejman Ghanouni, Xinrui Yan, Muneesh Tewari, Sanjiv S Gambhir
We have previously shown that low frequency ultrasound can release biomarkers from cells into the murine circulation enabling an amplification and localization of the released biomarker that could be used as a blood-based method to detect cancer earlier and monitor therapy. In this study, we further demonstrate that this technique could be used for characterization of tumors and/or identification of cellular masses of unknown origin due to the release of multiple protein and nucleic acid biomarkers in cells in culture, mice and patients...
2018: PloS One
Bo Li, Xiangsong Wu, Hanbei Chen, Chengle Zhuang, Zhiguo Zhang, Shuangshuang Yao, Dongsheng Cai, Guang Ning, Qing Su
MicroRNAs (miRNAs) are known to contribute to many metabolic diseases, including diabetes. In this study, we investigated the role of miR199a-5p in the regulation of hepatic insulin sensitivity. Ad-anti-miR199a-5p adenoviruses were injected into male C57BL/6J WT mice fed a high-fat diet to inhibit miR199a-5p expression before the glucose levels and insulin resistance were assessed. Similarly, Ad-miR199a-5p adenoviruses were injected into male C57BL/6J WT mice to cause the overexpression of miR199a-5p. To investigate the roles of autophagy-related protein 14 (ATG14) and miR199a-5p in the regulation of insulin sensitivity, we injected Ad-miR199a-5p with or without Ad-ATG14 viruses into WT C57BL/6J mice before performing functional assays...
March 14, 2018: Cell Death & Disease
Aaron Balasingam Koenig, Juan Martín Barajas, María Jose Guerrero, Kalpana Ghoshal
MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation of RNA followed by sequencing (CLIP-seq) have enabled transcriptome-wide identification of miRNA interactomes. In our study, we use a publicly available Argonaute-CLIP dataset (GSE97061), which contains nine HCC cases with matched benign livers, to characterize the miR-21 interactome in HCC...
March 14, 2018: International Journal of Molecular Sciences
Brunella Costanza, Andrei Turtoi, Akeila Bellahcène, Touko Hirano, Olivier Peulen, Arnaud Blomme, Vincent Hennequière, Eugene Mutijima, Jacques Boniver, Marie-Alice Meuwis, Claire Josse, Benjamin Koopmansch, Karin Segers, Takehiko Yokobori, Karim Fahmy, Marc Thiry, Carla Coimbra, Nancy Garbacki, Alain Colige, Dominique Baiwir, Vincent Bours, Edouard Louis, Olivier Detry, Philippe Delvenne, Masahiko Nishiyama, Vincent Castronovo
The identification of diagnostic and prognostic biomarkers from early lesions, measurable in liquid biopsies remains a major challenge, particularly in oncology. Fresh human material of high quality is required for biomarker discovery but is often not available when it is totally required for clinical pathology investigation. Hence, all OMICs studies are done on residual and less clinically relevant biological samples. Here after, we present an innovative, simple, and non-destructive, procedure named EXPEL that uses rapid, pressure-assisted, interstitial fluid extrusion, preserving the specimen for full routine clinical pathology investigation...
February 13, 2018: Oncotarget
Benjamin A Farber, Gadi Lalazar, Elana P Simon, William J Hammond, David Requena, Umesh K Bhanot, Michael P La Quaglia, Sanford M Simon
Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer found in adolescents and young adults without underlying liver disease. A deletion of ~400 kD has been found in one copy of chromosome 19 in the tumor tissue of all patients tested. This produces a fusion of the genes DNAJB1 and PRKACA which, in turn, produces a chimeric transcript and protein. Transcriptomic analysis of the tumor has shown upregulation of various oncologically relevant pathways, including EGF/ErbB, Aurora Kinase A, pak21 and wnt...
February 13, 2018: Oncotarget
Abdel-Rahman N Zekri, Enas Reda El-Sisi, Amira Salah El-Din Youssef, Mahmoud M Kamel, Auhood Nassar, Ola Sayed Ahmed, Mohamed El Kassas, Ahmed Barakat Barakat, Alaa Ismail Abd El-Motaleb, Abeer A Bahnassy
AIM: Molecular characterization of the CD133+ stem cells associated with hepatocarinogensis through identifying the expression patterns of specific microRNAs (miRNAs). METHODS: We investigated the expression pattern of 13 miRNAs in purified CD133+ cells separated from the peripheral blood of healthy volunteers, chronic hepatitis C (CHC), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) patients a long with bone marrow samples from the healthy volunteers and the LC patients using custom miScript miRNA PCR array...
2018: PloS One
Pan Li, Qingjian Ou, Todd A Braciak, Gong Chen, Fuat S Oduncu
Background: The poor clinical prognosis of Stage IIIB colon cancer patients is due in part to the current lack of an effective diagnostic method being available and highlights a need for the identification of novel biomarkers like microRNA (miRNA). Patients and methods: We used microarray analysis to compare the miRNA expression profiles of eight Stage IIIB colon cancer patients with worse clinical outcome (those who developed liver metastases between 8 and 18 months after surgery) against eight 'cured' Stage IIIB colon cancer patients (those who remained disease free following surgery during the same monitoring period)...
February 24, 2018: Japanese Journal of Clinical Oncology
Sobha Puppala, Cun Li, Jeremy P Glenn, Romil Saxena, Samer Gawrieh, Amy Quinn, Jennifer Palarczyk, Edward J Dick, Peter W Nathanielsz, Laura A Cox
Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high fat, high sucrose diet...
March 7, 2018: Journal of Physiology
Qingqing Feng, Wei-Dong Chen, Yan-Dong Wang
The gut microbiota, as the main member in gut microecology, is an essential mediator in health and disease. The gut microbiota interacts with various organs and systems in the body, including brain, lung, liver, bone, cardiovascular system, and others. Microbiota-derived metabolites such as the short chain fatty acid (SCFA) butyrate are primary signals, which link the gut microbiota and physiology. Recently, the gut microbiota has been identified as the origin of a number of diseases by influencing the related cell signaling pathways such as WNT/beta-catenin pathway in colorectal cancer and T cell receptor signaling in the central nervous system...
2018: Frontiers in Microbiology
P Scott Pine, Steven P Lund, Jerod R Parsons, Lindsay K Vang, Ashish A Mahabal, Luca Cinquini, Sean C Kelly, Heather Kincaid, Daniel J Crichton, Avrum Spira, Gang Liu, Adam C Gower, Harvey I Pass, Chandra Goparaju, Steven M Dubinett, Kostyantyn Krysan, Sanford A Stass, Debra Kukuruga, Kendall Van Keuren-Jensen, Amanda Courtright-Lim, Karol L Thompson, Barry A Rosenzweig, Lynn Sorbara, Sudhir Srivastava, Marc L Salit
BACKGROUND: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls. RESULTS: Three pure total human RNA samples (brain, liver, and placenta) and two different mixtures of these components were evaluated as measurement assurance control samples on multiple measurement systems at multiple sites and over multiple rounds...
March 6, 2018: BMC Genomics
Sadhbh O'Neill, Mette Bohl Larsen, Søren Gregersen, Kjeld Hermansen, Lorraine O'Driscoll
Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts...
February 6, 2018: Oncotarget
Kenny Schlosser, Mohamad Taha, Duncan J Stewart
There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV ) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A)...
2018: Theranostics
Joana Marquez, Ines Fernandez-Piñeiro, Marcos J Araúzo-Bravo, Gereon Poschmann, Kai Stühler, Abdel-Majid Khatib, Alejandro Sanchez, Fernando Unda, Gaskon Ibarretxe, Irantzu Bernales, Iker Badiola
Phenotypic transformation of liver sinusoidal endothelial cells is one of the most important stages of liver metastasis progression. The miRNA effects on liver sinusoidal endothelial cells during liver metastasis have not yet been studied. Herein, whole genome analysis of miRNA expression in these cells during colorectal liver metastasis revealed repressed expression of microRNA-20a. Importantly, downregulation of miR-20a occurs in parallel with upregulation of its known protein targets. To restore normal miR-20a levels in liver sinusoidal endothelial cells, we developed chondroitin sulfate-sorbitan ester nanoparticles conjugated with miR-20a in a delivery system that specifically targets liver sinusoidal endothelial cells...
February 28, 2018: International Journal of Cancer. Journal International du Cancer
Takuma Iguchi, Ken Sakurai, Satoshi Tamai, Kazuhiko Mori
Circulating microRNAs (miRNAs) can potentially be used as sensitive and specific biomarkers for tissue injury. However, the usefulness of circulating miRNAs as safety biomarkers in nonclinical toxicological studies using nonhuman primates is debatable owing to the limited information on organ-specific miRNAs. Therefore, a systematic investigation was performed to address this point. We identified organ-specific miRNAs from cynomolgus monkeys by next-generation sequencing analysis, which revealed that miR-122 was only abundant in the liver, whereas miR-192 was abundant in the liver, stomach, intestines, and kidney...
January 2018: Journal of Toxicologic Pathology
Chi Han Li, Shing Chun Tang, Chi Hin Wong, Yan Wang, Jian-Dong Jiang, Yangchao Chen
Berberine is a Chinese herbal medicine extracted from rhizoma coptidis that functions to improve insulin resistance, hyperlipidemia, hepatosteatosis and inflammation. Berberine can modify the activity of cell metabolism and signaling pathways by regulating expression of genes. However, the roles and effects of differential microRNA (miRNA) expression induced by berberine treatment are largely unexplored. It is believed that miRNAs expression modified by berberine contributes to its therapeutic effects to diseases such as hepatosteatosis and non-alcoholic fatty liver disease...
February 22, 2018: European Journal of Pharmacology
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