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Steven Mullenbrock, Fei Liu, Suzanne Szak, Xiaoping Hronowski, Benbo Gao, Peter Juhasz, Chao Sun, Mei Liu, Helen McLaughlin, Qiurong Xiao, Carol Feghali-Bostwick, Timothy S Zheng
Fibroblasts/myofibroblasts are the key effector cells responsible for excessive extracellular matrix (ECM) deposition and fibrosis progression in both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) patient lungs, thus it is critical to understand the transcriptomic and proteomic programs underlying their fibrogenic activity. We conducted the first integrative analysis of the fibrotic programming in these cells at the levels of gene and microRNA (miRNA) expression, as well as deposited ECM protein to gain insights into how fibrotic transcriptional programs culminate in aberrant ECM protein production/deposition...
November 29, 2018: Genes
Corrie L Gallant-Behm, Joseph Piper, Joshua M Lynch, Anita G Seto, Seok Jong Hong, Thomas A Mustoe, Catherine Maari, Linda A Pestano, Christina M Dalby, Aimee L Jackson, Paul Rubin, William S Marshall
MicroRNA-29 negatively regulates fibrosis, and miR-29 is downregulated in multiple fibrotic organs and tissues, including in the skin. miR-29 mimics prevent pulmonary fibrosis in mouse models but have not previously been tested in the skin. This study aimed to identify pharmacodynamic (PD) biomarkers of miR-29 in mouse skin, to translate those biomarkers across multiple species and to assess the PD activity of a miR-29b mimic (remlarsen) in a clinical trial. miR-29 biomarkers were selected based on gene function and mRNA expression using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR)...
November 22, 2018: Journal of Investigative Dermatology
K Zhang, Z Ma, W Wang, R Liu, Y Zhang, M Yuan, G Li
BACKGROUND: Atrial remodeling in the form of fibrosis is considered the basis in the development of atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on atrial remodeling induced by chronic intermittent hypoxia (CIH) and the mechanisms underlying such changes. METHODS: A total of 45 Sprague-Dawley rats were randomized into three groups: control group, CIH group, CIH with doxycycline treatment (CIH-D) group. A rat model of atrial remodeling was established by CIH and Masson staining was used to evaluate the extent of atrial fibrosis...
November 23, 2018: Herz
Maria Enoia Dantas da Costa E Silva, Evelise Regina Polina, Daisy Crispim, Renan Cesar Sbruzzi, Daniel Lavinsky, Felipe Mallmann, Nidiane Carla Martinelli, Luis Henrique Canani, Katia Gonçalves Dos Santos
MicroRNAs (miRNAs/miRs) are involved in the pathogenesis of diabetes mellitus and its chronic complications, and their circulating levels have emerged as potential biomarkers for the development and progression of diabetes. However, few studies have examined the expression of miRNAs in diabetic retinopathy (DR) in humans. This case-control study aimed to investigate whether the plasma levels of miR-29b and miR-200b are associated with DR in 186 South Brazilians with type 2 diabetes (91 without DR, 46 with non-proliferative DR and 49 with proliferative DR)...
November 23, 2018: Journal of Cellular and Molecular Medicine
Ning-Sheng Lai, Hui-Chun Yu, Chien-Hsueh Tung, Kuang-Yung Huang, Hsien-Bin Huang, Ming-Chi Lu
BACKGROUND: Interleukin (IL)-23 can facilitate the differentiation of IL-17-producing helper T cells (Th17). The IL-23/IL-17 axis is known to play a key role in the immunopathogenesis of ankylosing spondylitis (AS). We hypothesized that the expression of microRNAs (miRNAs, miRs) would be regulated by IL-23 and that these miRNAs could participate in the immunopathogenesis of AS. METHODS: Expression profiles of human miRNAs in K562 cells, cultured in the presence or absence of IL-23 for 3 days, were analyzed by microarray...
November 21, 2018: Arthritis Research & Therapy
Adamantios V Mavrogiannis, Ioanna Kokkinopoulou, Christos K Kontos, Diamantis C Sideris
Background - Treatment of cancer with natural chemotherapeutic agents induces apoptosis along with remarkable alterations in the expression of apoptosis-related genes. Deregulation of microRNA (miRNA) expression is implicated in several human malignancies. Vinca alkaloids compose a class of antimitotic drugs preventing cancer cells from dividing, leading to apoptosis. They are commonly used in clinical practice for breast cancer treatment. Objective - The present study focused on the effects of vinca alkaloids (vincristine, vinblastine, and vinorelbine) on miRNA expression of treated breast cancer cells...
November 11, 2018: Current Pharmaceutical Biotechnology
Tao Wang, Jingjing Hou, Shuo Jian, Qicong Luo, Jie Wei, Zengpeng Li, Xuegang Wang, Peide Bai, Bo Duan, Jinchun Xing, Jianchun Cai
MicroRNAs (miRNAs) are important regulators and associated with the development of many different types of cancer, including gastric cancer. However, their pathophysiologic role and their relevance to tumorigenesis, invasion and metastasis are still unknown. In our current study, we performed microRNA array and found that 28 of miRNAs were differentially expressed in INF type of gastric cancer. Among 28 miRNAs, miR-29b was one of the most significantly down-regulated miRNA. Further bioinformatics analysis showed that MMP2 was a potential target of miR-29b...
2018: Journal of Cancer
Xiaolan Chen, Hongjia Ouyang, Zhijun Wang, Biao Chen, Qinghua Nie
It is well known that fibroblast growth factor receptor 2 ( FGFR2 ) interacts with its ligand of fibroblast growth factor ( FGF ) therefore exerting biological functions on cell proliferation and differentiation. In this study, we first reported that the FGFR2 gene could generate a circular RNA of circFGFR2, which regulates skeletal muscle development by sponging miRNA. In our previous study of circular RNA sequencing, we found that circFGFR2, generated by exon 3⁻6 of FGFR2 gene, differentially expressed during chicken embryo skeletal muscle development...
November 6, 2018: Cells
Yun-Qiang Wan, Jian-Guo Feng, Mao Li, Mao-Zhou Wang, Li Liu, Xueru Liu, Xiao-Xia Duan, Chun-Xiang Zhang, Xiao-Bin Wang
Ketamine has a rapid, obvious, and persistent antidepressant effect, but its underlying molecular mechanisms remain unknown. Recently, microRNAs (miRNAs) have emerged as important modulators of ketamine's antidepressant effect. We investigated the alteration in miR-29b-3p in the brain of rats subjected to ketamine administration and chronic unpredictable mild stress (CUMS), and a sucrose preference test and forced swimming test were used to evaluate the rats' depressive-like state. We used recombination adeno-associated virus (rAAV) or lentivirus-expressing miR-29b-3p to observe the change in metabotropic glutamate receptor 4 (GRM4)...
October 29, 2018: Experimental & Molecular Medicine
Michael J G Milevskiy, Gurveen K Sandhu, Anna Wronski, Darren Korbie, Brooke L Brewster, Annette Shewan, Stacey L Edwards, Juliet D French, Melissa A Brown
Depletion of BRCA1 protein in mouse mammary glands results in defects in lactational development and increased susceptibility to mammary cancer. Extensive work has focussed on the role of BRCA1 in the normal breast and in the development of breast cancer, the cell of origin for BRCA1 tumours and the protein-coding genes altered in BRCA1 deficient cells. However, the role of non-coding RNAs in BRCA1-deficient cells is poorly understood. To evaluate miRNA expression in BRCA1 deficient mammary cells, RNA sequencing was performed on the mammary glands of Brca1 knockout mice...
September 11, 2018: Oncotarget
Brendan M Browne, Kristian D Stensland, Chintan K Patel, Travis Sullivan, Eric J Burks, David Canes, Jay D Raman, Joshua Warrick, Kimberly M Reiger-Christ
OBJECTIVE: To evaluate microRNA biomarkers for upper tract urothelial carcinoma (UTUC) to improve risk stratification. METHODS: MicroRNA was isolated from 157 radical nephroureterectomy (RNU) specimens from two institutions. The relative expression of miRNA was examined for high grade versus low grade tumors as well as muscle invasive versus non-muscle invasive tumors. Recurrence free survival (RFS) and overall survival (OS) were also stratified using relative expression of specific miRNA...
October 10, 2018: Urology
Pradeep Kumar, Reben Raeman, Daniel M Chopyk, Tekla Smith, Kiran Verma, Yunshan Liu, Frank A Anania
Adiponectin inhibits hepatic stellate cell (HSC) activation and subsequent development of liver fibrosis via multiple mechanisms. Phosphatase and tensin homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation, but its regulation by adiponectin is not fully understood. Here, we investigated the effect of adiponectin on PTEN in LX-2 cells, a human cell line and examined the underlying molecular mechanisms involved in adiponectin-mediated upregulation of PTEN activity during fibrosis. PTEN expression was found to be significantly reduced in the livers of mice treated with CCl4 , whereas its expression was rescued by adiponectin treatment...
October 2018: Biochimica et biophysica acta. Molecular basis of disease
Jia Liu, Yanrong Wen, Hui He, Hong-Yuan Chen, Zhen Liu
MicroRNAs (miRNAs) regulate the expression of mRNAs in cells. The determination of subcellular miRNAs in single living cells is essential for understanding the subcellular localizations and functions of miRNAs as well as the microheterogeneity of cells. However, current approaches fail either to keep the cells alive or maintain their original cellular composition or are unable to provide subcellular resolution. Herein, we presented a new approach, called plasmonic affinity sandwich assay (PASA), for rapid and ultrasensitive probing of trace cytoplasmic and nuclear miRNAs in single living cells...
September 28, 2018: Chemical Science
João V Esteves, Caio Y Yonamine, Danilo C Pinto-Junior, Frederico Gerlinger-Romero, Francisco J Enguita, Ubiratan F Machado
The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus (DM). MicroRNAs (miRNAs) have emerged as important modulators of mRNA/protein expression, but their role in DM is unclear. We investigated miRNAs hypothetically involved in GLUT4/HK2 expression in soleus muscle of type 1 diabetes-like rats. In silico analysis revealed 651 miRNAs predicted to regulate solute carrier family 2 member 4 ( Slc2a4 ) mRNA, several of them also predicted to regulate Hk2 mRNA, and 16 miRNAs were selected for quantification...
2018: Frontiers in Endocrinology
Mona Moniri, Amin Boroumand Moghaddam, Susan Azizi, Raha Abdul Rahim, Saad Wan Zuhainis, Mohammad Navaderi, Rosfarizan Mohamad
Background: In recent years, bacterial nanocellulose (BNC) based nanocomposites have been developed to promote healing property and antibacterial activity of BNC wound dressing. Molecular study can help to better understanding about interaction of genes and pathways involved in healing progression. Objectives: The aim of this study was to prepare bacterial nanocellulose/silver (BNC/Ag) nanocomposite films as ecofriendly wound dressing in order to assess their physical, cytotoxicity and antimicrobial properties...
2018: International Journal of Nanomedicine
Faqing Liang, Meng Yang, Ning Tong, Jinju Fang, Yanbin Pan, Jianmin Li, Xiao Zhang
Breast Cancer (BC) is one of the most common primary malignant tumors, which is life threatening. Previous studies have demonstrated that microRNAs (miRNA) may regulate or affect the incidence of BC. However, results of these studies are inconsistent, due to factors including the different sequencing platforms and sample selection methods used. To explore the key miRNAs involved in the pathogenesis of BC, and to use these miRNAs to monitor the tumor progression of BC, a systematic review was performed on the previous studies examining BC miRNA; the function of the target genes that were modulated by these key miRNAs were also analyzed...
October 2018: Oncology Letters
Zhi Huang, Lu Lu, Tianpeng Jiang, Shuai Zhang, Yaping Shen, Zhu Zheng, Ansu Zhao, Rui Gao, Rui Li, Shi Zhou, Jing Liu
The present study aimed to determine whether an miRNA (miR)-29b inhibitor protected against cerebral ischemia/reperfusion (I/R) injury in vitro and to investigate the underlying mechanisms. As a model for induced cerebral IR injury, N2a cells were exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) environment. Using this model, it was demonstrated that miR-29b was significantly upregulated compared with cells in a normal environment. The interactions between miR-29b and myeloid cell leukemia sequence (MCL)-1 were then investigated using dual-luciferase assays, revealing a strong regulation of MCL-1 through the 3'untranslated region...
October 2018: Experimental and Therapeutic Medicine
Qian-Ru Sun, Xiong Zhang, Kun Fang
BACKGROUND Phenotypic switch of vascular smooth muscle cells (VSMCs) participates in the etiology of various vascular diseases. It has been proved that microRNAs (miRNAs) serve as crucial regulators of functions of VSMCs. This study aimed to discover how miR-29b regulates the transformation of VSMCs phenotypes in mice. MATERIAL AND METHODS Primary VSMCs of aorta in mice were cultured in DMEM medium. A series of experiments involving transfection of oligonucleotides in cultured VSMCs, quantitative reverse transcription PCR (qRT-PCR), luciferase reporter assay, and Western blotting analysis were performed in this study...
September 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Manjari Baluni, Sneha Ghildiyal, Dharamveer Singh, D Himanshu Reddy, Rashmi Kumar, Tapan N Dhole
BACKGROUND: Japanese encephalitis virus (JEV) is a neurotropic mosquito-borne Flavivirus, mainly prevalent in Asia. It is the most important causative agent of acute viral encephalitis in humans. Recently, micro RNAs are discovered as a key regulator of inflammatory and immune responses in various diseases including neurological and viral infections. Thus, this study was proposed to check whether changes in cellular miRNA expression due to JE virus infection, can be detected in circulation which would be helpful in diagnosis and treatment...
October 15, 2018: Journal of Neuroimmunology
Steven D Scoville, Ansel P Nalin, Luxi Chen, Li Chen, Michael H Zhang, Kathleen McConnell, Susana Beceiro Casas, Gabrielle Ernst, Abd Al-Rahman Traboulsi, Naima Hashi, Monica Williams, Xiaoli Zhang, Tiffany Hughes, Anjali Mishra, Don M Benson, Jennifer N Saultz, Jianhua Yu, Aharon G Freud, Michael A Caligiuri, Bethany L Mundy-Bosse
Acute myeloid leukemia (AML) can evade the mouse and human innate immune system by suppressing natural killer (NK) cell development and NK cell function. This is driven in part by the overexpression of microRNA (miR)-29b in the NK cells of AML patients, but how this occurs is unknown. In the current study, we demonstrate that the transcription factor aryl hydrocarbon receptor (AHR) directly regulates miR-29b expression. We show that human AML blasts activate the AHR pathway and induce miR-29b expression in NK cells, thereby impairing NK cell maturation and NK cell function, which can be reversed by treating NK cells with an AHR antagonist...
October 25, 2018: Blood
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