Bone marrow derived-mesenchymal stem cells downregulate IL17A dependent IL6/STAT3 signaling pathway in CCl4-induced rat liver fibrosis
PLOS ONE
Authors: Farouk, Shimaa; Sabet, Salwa; Abu Zahra, Fatma A.; El-Ghor, Akmal A.
Abstract
Therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been reported in several animal models of liver fibrosis. Interleukin (IL) 17A, IL6 and Stat3 have been described to play crucial roles in chronic liver injury. However, the modulatory effect of MSCs on these markers was controversial in different diseases. BM-MSCs might activate the IL6/STAT3 signaling pathway and promote cell invasion in hepatocellular carcinoma, but the immunomodulatory role of BM-MSCs on IL17A/IL6/STAT3 was not fully elucidated in liver fibrosis. In the present study, we evaluated the capacity of the BM-MSCs in the modulation of cytokines milieu and signal transducers, based on unique inflammatory genes Il17a and Il17f and their receptors Il17rc and their effect on the IL6/STAT3 pathway in CCl4-induced liver fibrosis in rats. A single dose of BM-MSCs was administered to the group with induced liver fibrosis, and the genes and proteins of interest were evaluated along six weeks after treatment. Our results showed a significant downregulation of Il17a, Il17ra,il17f and Il17rc genes. In accordance, BM-MSCs administration declined IL17, IL2 and IL6 serum proteins and downregulated IL17A and IL17RA proteins in liver tissue. Interestingly, BM-MSCs downregulated both Stat3 mRNA expression and p-STAT3, while Stat5a gene was downregulated and p-STAT5 protein was elevated. Also P-SMAD3 and TGF beta R2 proteins were downregulated in response to BM-MSCs treatment. Collectively, we suggest that BM-MSCs might play an immunomodulatory role in the treatment of liver fibrosis through downregulation of IL17A affecting IL6/STAT3 signaling pathway.
Global interlaboratory assessments of perfluoroalkyl substances under the Stockholm Convention on persistent organic pollutants
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
Authors: Fiedler, H.; van der Veen, I; de Boer, J.
Abstract
The Global Monitoring Plan (GMP) according to article 16 of the Stockholm Convention on Persistent Organic Pollutants (POPs) requires that POP laboratories must be capable - at any time - to analyse samples for POPs within a variation of +/- 25%. Based on this target error of 25%, a statistical model using z-scores was applied to assess the performance of analytical laboratories for POPs and a number of matrices. Since the second round of these 'Bi-ennial Global Interlaboratory Assessment on Persistent Organic Pollutants (POPs)', carried out in 2012/2013, perfluoroalkyl substances (PFASs) have been included into the proficiency tests. The third round was carried out in 2016/2017. The test materials included test solutions of PFASs analytical standards, the abiotic matrices sediment, air (extract) and water and the biotic matrices fish, human milk and human plasma. The number of laboratories submitting results for PFASs remained quite stable (IL2 = 27 laboratories; IL3 = 29), but there was broader geographic distribution observed in IL3: in addition to the laboratories from Asia and the Western Europe/other groups, two laboratories from Africa participated, two from Central-Eastern Europe and one from the Latin American/Caribbean region. Considering that PFASs were introduced for the first time in round 2, the results were good to reasonable compared to those of a number of other POPs included in the same study. However, it shall also be mentioned that for some matrices and PFASs, the number of laboratories submitting results was too small and the results too scattered to derive a consensus value. This was especially true for the PFOS precursor compounds and the air matrix. Also, laboratories struggle with the analysis of the branched PFOS isomers. These interlaboratory assessments on PFASs gave promising results and demonstrated the importance of proficiency tests in an international environment to generate trust in laboratory results. The need to participate regularly in such intercomparison assessments is highlighted. The results show the current level of PFAS analysis, which varies by laboratory and by matrix rather than per geographic region. (C) 2019 Elsevier B.V. All rights reserved.