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Pradip B Devhare, Robert Steele, Adrian M Di Bisceglie, David E Kaplan, Ratna B Ray
African Americans (AA) have higher hepatocellular carcinoma (HCC) and mortality rates than Caucasians Americans (CA). Chronic hepatitis C virus (HCV) infection leads to cirrhosis and HCC. HCV infection is highly prevalent in AA population compared to other racial groups. African Americans are also less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV. However, the explanation for this disparity is currently unknown. Circulating microRNAs (miRNAs) in the blood are emerging as biomarkers for pathological conditions...
October 19, 2016: Gene Expression
Jamal El-Saghir, Farah Nassar, Nadim Tawil, Marwan El-Sabban
BACKGROUND: Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia...
October 19, 2016: Retrovirology
Xingwei Jiang, Tingting Zhou, Yan Xiao, Jiahui Yu, Shuaijie Dou, Guojiang Chen, Renxi Wang, He Xiao, Chunmei Hou, Wei Wang, Qingzhu Shi, Jiannan Feng, Yuanfang Ma, Beifen Shen, Yan Li, Gencheng Han
T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, shows therapeutic potential. However, the molecular mechanism by which Tim-3 regulates immune responses remains to be determined. In particular, very little is known about how Tim-3 works in innate immune cells. Here, we demonstrated that Tim-3 is involved in the development of tumor-promoting M2 macrophages in colon cancer. Manipulation of the Tim-3 pathway significantly affected the polarization status of intestinal macrophages and the progression of colon cancer...
2016: Oncoimmunology
Stephen Harrap
Genetic discovery in blood pressure is generally referenced in relation to protein-coding genes, despite the fact that genes less than 2% of the genome. Recent exploration of the DNA sequences between genes, once called "junk" DNA, has revealed a wealth of transcripts for RNA species that do not encode protein. These non-coding RNAs (ncRNAs) have emerged as dynamic managers of the business of the genome, able to coordinate the expression of genes in time and space to achieve the complexities of normal development and growth...
September 2016: Journal of Hypertension
Wafaa M Ezzat, Khalda Said Amr, Haiam Abdel Raouf, Yasser A Elhosary, Abdelfattah E Hegazy, Hoda H Fahim, Refaat R Kamel
BACKGROUND AND AIMS: Activation of telomerase reverse transcriptase (hTERT) has a role in liver carcinogenesis where telomerase is normally suppressed in most human somatic tissues after birth. In the current study we aimed to detect the significance of hTERT mRNA in early detection of hepatocellular carcinoma (HCC) and to determine the relationship between serum microRNA155 and telomerase expression. METHODS: Serum and liver tissue samples were collected from 40 patients (17 samples from patients with liver cirrhosis and 23 samples from patients with HCC) and 12 blood samples from healthy subjects were collected...
July 2016: Archives of Medical Research
Yang Yang, Ben-Quan Wu, Yan-Hong Wang, Yun-Feng Shi, Jin-Mei Luo, Jun-Hui Ba, Hui Liu, Tian-Tuo Zhang
Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments...
October 18, 2016: Immunopharmacology and Immunotoxicology
Dongqing Kong, Sai Bi, Zonghua Wang, Jianfei Xia, Feifei Zhang
In this work, an in situ growth protocol is introduced to fabricate three-dimensional graphene films (3D GFs) on gold substrates, which are successfully utilized as working electrode for electrochemical detection of nucleic acid (microRNA) and protein (lysozyme) based on a signal-on sensing mechanism. To realize the bridge between the gold substrate and graphene film, a monolayer of 4-aminothiophenol is self-assembled on the substrate, which is then served as connectors for the growth of 3D GFs on the gold substrate by the hydrothermal reduction (HR) technique...
October 18, 2016: Analytical Chemistry
Mariola Kurowska-Stolarska, Manhl K Hasoo, David J Welsh, Lynn Stewart, Donna McIntyre, Brian E Morton, Steven Johnstone, Ashley M Miller, Darren L Asquith, Neal L Millar, Ann B Millar, Carol A Feghali-Bostwick, Nikhil Hirani, Peter J Crick, Yuqin Wang, William J Griffiths, Iain B McInnes, Charles McSharry
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF therefore microRNAs may reveal novel pathogenic pathways. OBJECTIVES: To determine the regulatory role of microRNA(miR)-155 in the pro-fibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts and its contribution to experimental pulmonary fibrosis...
October 13, 2016: Journal of Allergy and Clinical Immunology
N Narayan, L Morenos, B Phipson, S N Willis, G Brumatti, S Eggers, N Lalaoui, L M Brown, H J Kosasih, R C Bartolo, L Zhou, D Catchpoole, R Saffery, A Oshlack, G J Goodall, P G Ekert
Enforced expression of miR-155 in myeloid cells has been shown to have both oncogenic or tumour suppressor functions in acute myeloid leukemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML datasets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favors selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Deguang Yang, Jinhong Wang, Meng Xiao, Tao Zhou, Xu Shi
Stem-cell-based therapy for cardiovascular disease, especially ischemic heart disease (IHD), is a promising approach to facilitating neovascularization through the migration of stem cells to the ischemic site and their subsequent differentiation into endothelial cells (ECs). Hypoxia is a chief feature of IHD and the stem cell niche. However, whether hypoxia promotes stem cell differentiation into ECs or causes them to retain their stemness is controversial. Here, the differentiation of pluripotent stem cells (iPSCs) into endothelial cells (ECs) was induced under hypoxia...
October 12, 2016: Scientific Reports
Kevin Appourchaux, Safi Dokmak, Matthieu Resche-Rigon, Xavier Treton, Martine Lapalus, Charles-Henry Gattolliat, Emmanuelle Porchet, Michelle Martinot-Peignoux, Nathalie Boyer, Michel Vidaud, Pierre Bedossa, Patrick Marcellin, Ivan Bièche, Emilie Estrabaud, Tarik Asselah
Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with chronic hepatitis B (CHB) and C (CHC). The expression of 13 fibrosis-related microRNAs (miRNAs) (miR-20a, miR-21, miR-27a, miR-27b, miR-29a, miR-29c, miR-92a, miR-122, miR-146a, miR-155, miR-221, miR-222, and miR-224) was analyzed in 194 serums and 177 liver biopsies of patients with either CHB or CHC to develop models to diagnose advanced fibrosis and cirrhosis (Metavir F3-F4). In CHB patients, the model (serum miR-122, serum miR-222, platelet count and alkaline phosphatase) was more accurate than APRI and FIB-4 to discriminate in between mild and moderate fibrosis (F1-F2) and F3-F4 (AUC of CHB model: 0...
October 12, 2016: Scientific Reports
Agata A Filip, Anna Grenda, Sylwia Popek, Dorota Koczkodaj, Małgorzata Michalak-Wojnowska, Michał Budzyński, Ewa Wąsik-Szczepanek, Szymon Zmorzyński, Agnieszka Karczmarczyk, Krzysztof Giannopoulos
Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes...
October 12, 2016: Annals of Hematology
Hui Wang, Yihua Bei, Peipei Huang, Qiulian Zhou, Jing Shi, Qi Sun, Jiuchang Zhong, Xinli Li, Xiangqing Kong, Junjie Xiao
Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR)-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS). However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg) and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects...
October 11, 2016: Molecular Therapy. Nucleic Acids
Jianjun Wang, Zhiyong Deng, Zeyou Wang, Jianhong Wu, Tao Gu, Yibiao Jiang, Guangxin Li
Exosomes containing microRNA-155 act as molecule carriers during immune cell-cell communication and play an important role in the inflammatory response of H. pylori infection macrophages. Previous reports have found that miR-155 was over-expressed in H. pylori infection macrophages, but the significance of which is still unknown. In this study, we analyzed the impact of miR-155 loaded in exosomes derived from macrophages to the inflammatory response of H. pylori infection macrophages and possible mechanisms...
2016: American Journal of Translational Research
Shizhi Wang, Xiaoli Cao, Bo Ding, Jinfeng Chen, Mengjing Cui, Yuling Xu, Xiaoyun Lu, Zhengdong Zhang, Aiqin He, Hua Jin
Genetic variants in miRNAs have attracted more and more attention these years because they are capable of altering miRNA function and/or expression, consequently affecting downstream biological pathways and disease risk. The rs767649 polymorphism, locating in the promoter of miR-155, was recently reported to be able to alter transcriptional activity of miR-155 and relate to lung cancer risk. In this study, we aimed to assess the relationship between rs767649 and cervical cancer (CC) risk. We investigated the association of rs767649 with CC risk in a two-stage case-control study with 1157 cases and 1280 controls...
October 4, 2016: Gene
Bruno J Conti, Karina B Santiago, Eliza O Cardoso, Paula P Freire, Robson F Carvalho, Marjorie A Golim, José M Sforcin
OBJECTIVES: Dendritic cells (DCs) are antigen-presenting cells, essential for recognition and presentation of pathogens to T cells. Propolis, a resinous material produced by bees from various plants, exhibits numerous biological properties, highlighting its immunomodulatory action. Here, we assayed the effects of propolis on the maturation and function of human DCs. METHODS: DCs were generated from human monocytes and incubated with propolis and LPS. NF-κB and cytokines production were determined by ELISA...
October 7, 2016: Journal of Pharmacy and Pharmacology
Wei Yuan, Wanyan Tang, Yibin Xie, Shaoming Wang, Yingtai Chen, Jun Qi, Youlin Qiao, Jie Ma
INTRODUCTION: Lack of diagnostic makers results in loss of operation opportunity in that most patients are diagnosed at the late stage. Pancreatic cancer (PC) has been regarded as a fatal disease with a 5-year survival rate below 10%. Therefore, the development of diagnostic biomarkers for PC is in urgent need to control the mortality of the disease. MATERIALS AND METHODS: This is a case-control study including 640 plasma samples from healthy controls (HC), patients with benign pancreatic diseases (BPD), patients with PC; and patients with other gastrointestinal (GI) cancers...
October 3, 2016: Oncotarget
Xiaolin Lin, Yujuan Qin, Junshuang Jia, Taoyan Lin, Xia Lin, Li Chen, Hui Zeng, Yanjiang Han, Lihong Wu, Shun Huang, Meng Wang, Shenhao Huang, Raoying Xie, Liqi Liang, Yu Liu, Ruiyu Liu, Tingting Zhang, Jing Li, Shengchun Wang, Penghui Sun, Wenhua Huang, Kaitai Yao, Kang Xu, Tao Du, Dong Xiao
miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function...
October 2016: PLoS Genetics
R X Hou, R F Liu, X C Zhao, Y R Jia, P An, Z P Hao, J Q Li, X H Li, G H Yin, K M Zhang
Mesenchymal stem cells (MSCs) have pleiotropic immuno-modulatory effects and pro-angiogenic ability, leading to the presumption that MSCs may be involved in the pathogenesis of many inflammatory or autoimmune disorders, including psoriasis. In a previous study, we reported the specific gene expression profile of dermal MSCs from psoriasis. Inflammation- and angiogenesis-related genes, such as lipopolysaccharide-induced tumor necrosis factor-alpha transcription factor (LITAF), dual-specificity protein phosphatase 1 (DUSP1), vascular endothelial growth factor α (VEGFα), and insulin-like growth factor-binding protein-5 (IGFBP5), are abnormally expressed in psoriatic dermal MSCs...
September 2, 2016: Genetics and Molecular Research: GMR
Jesús García-Donas, Benoit Beuselinck, Lucía Inglada-Pérez, Osvaldo Graña, Patrick Schöffski, Agnieszka Wozniak, Oliver Bechter, Maria Apellániz-Ruiz, Luis Javier Leandro-García, Emilio Esteban, Daniel E Castellano, Aranzazu González Del Alba, Miguel Angel Climent, Susana Hernando, José Angel Arranz, Manuel Morente, David G Pisano, Mercedes Robledo, Cristina Rodriguez-Antona
The majority of metastatic renal cell carcinoma (RCC) patients are treated with tyrosine kinase inhibitors (TKI) in first-line treatment; however, a fraction are refractory to these antiangiogenic drugs. MicroRNAs (miRNAs) are regulatory molecules proven to be accurate biomarkers in cancer. Here, we identified miRNAs predictive of progressive disease under TKI treatment through deep sequencing of 74 metastatic clear cell RCC cases uniformly treated with these drugs. Twenty-nine miRNAs were differentially expressed in the tumors of patients who progressed under TKI therapy (P values from 6 × 10(-9) to 3 × 10(-3))...
July 7, 2016: JCI Insight
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