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      Evaluation of miR-9 and miR-143 expression in urine specimens of sulfur mustard exposed patients

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          Abstract

          Sulfur mustard (SM) or mustard gas is a chemical alkylating agent that causes blisters in the skin (blister gas), burns the eyes and causes lung injury. Some major cellular pathways are involved in the damage caused by mustard gas such as NF-κb signaling, TGF-β signaling, WNT pathway, inflammation, DNA repair and apoptosis. MicroRNAs are non-coding small RNAs (19–25 nucleotides) that are involved in the regulation of gene expression and are found in two forms, extracellular and intracellular. Changes in the levels of extracellular microRNAs are directly associated with many diseases, it is thus common to study the level of extracellular microRNAs as a biomarker to determine the pathophysiologic status. In this study, 32 mustard gas injured patients and 32healthy subjects participated. Comparative evaluation of miR-9 and miR-143 expression in urine samples was performed by Real Time PCR and Graph Pad software. The Mann Whitney t-test analysis of data showed that the expression level of miR-143 and miR-9 had a significant decrease in sulfur mustard individuals with the respective p-value of 0.0480 and 0.0272 compared to normal samples, with an imbalance of several above mentioned pathways. It seems that reducing the expression level of these genes has a very important role in the pathogenicity of mustard gas injured patients.

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          Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

          To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.
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            The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation.

            Nuclear factor kappa B (NF-κB) transcription factors are evolutionarily conserved, coordinating regulators of immune and inflammatory responses. They also play a pivotal role in oncogenesis and metabolic disorders. Several studies during the past two decades have highlighted the key role of the IKK/NF-κB pathway in the induction and maintenance of the state of inflammation that underlies metabolic diseases such as obesity and type 2 diabetes. Recent reports, however, reveal an even more intimate connection between NF-κB and metabolism. These studies demonstrate that NF-κB regulates energy homeostasis via direct engagement of the cellular networks governing glycolysis and respiration, with profound implications beyond metabolic diseases, including cancer, ageing and anticancer therapy. In this review, we discuss these emerging bioenergetic functions of NF-κB and their significance to oncogenesis. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products.

              Recent baby formula milk powder contamination incidents have shown that the classic markers or standards in milk quality control are insufficient in identifying "manipulated" poor-quality milk. In the present study, we demonstrated for the first time that cow milk contains large amounts of microRNAs (miRNAs) and that the unique expression profile of milk-specific miRNAs can serve as a novel indicator and possible new standard for the quality control of raw milk and milk-related commercial products, such as fluid milk and powdered formula milk. First, using Solexa sequencing, we systematically screened miRNA expression in raw milk and identified a total of 245 miRNAs in raw milk. Unlike other classic biomarkers whose expression levels are nearly identical at different periods of lactation, individual miRNAs can be significantly altered during lactation process, implicating that miRNAs may be a more accurate indicator to reflect the quality alteration of milk. Second, using TaqMan probe-based miRNA quantitative RT-PCR, we further identified seven miRNAs that have a relatively consistent expression throughout the lactation process, and more importantly, the expression profile of these seven milk-specific miRNAs can serve as an ideal biomarker for discriminating poor-quality or "manipulated" milk from pure raw milk, as well as for the quality control of commercial milk products, such as fluid milk and powdered formula milk. Together, our findings provide a basis for understanding the physiological role of milk miRNAs and a new potential standard for determining the quality of raw milk or milk-related commercial products.
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                Author and article information

                Journal
                Interdiscip Toxicol
                Interdiscip Toxicol
                ITX
                Interdisciplinary Toxicology
                Slovak Toxicology Society SETOX
                1337-6853
                1337-9569
                December 2015
                December 2015
                : 8
                : 4
                : 169-174
                Affiliations
                [1 ]Human Genetic Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran
                [2 ]Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran
                [3 ]Iranian Blood Transfusion Organization Research Center, Tehran, Iran
                [4 ]System Biology Institute, Chemical injuries Research Center, Baqiyatallah Medical Sciences University, Tehran, Iran
                Author notes
                Correspondence address: Mahmood Tavallaie, PhD., Baqiyatallah University of Medical Sciences, Human Genetic Research Center, Tehran, Iran. TEL.: +9826403292. E-MAIL: tavalla.mah@ 123456gmail.com
                Article
                ITX-8-169
                10.1515/intox-2015-0026
                4961915
                27486378
                b3faa4f3-c95c-4e7d-860b-177bc8d8f3f3
                Copyright © 2015 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 June 2015
                : 08 December 2015
                : 10 December 2015
                Categories
                Original Article

                Toxicology
                mustard,microrna,bronchiolitis,apoptosis,inflammation,pathways
                Toxicology
                mustard, microrna, bronchiolitis, apoptosis, inflammation, pathways

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