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Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
In this study, we sought to investigate whether SH0165 (serovar 5, high-virulent strain) and HN0001 (serovar 6, non-virulent strain) infection induces autophagy and the specific role of autophagy in bacterial invasion and inflammation during H. parasuis infection. Moreover, we explored the mechanism underlying autophagy regulated inflammation through inflammatory signaling cascades during H. parasuis infection. This observation could provide useful information for further understanding the role of autophagy in H. parasuis infection and improve our knowledge of new strategies against this pathogen. Materials and Methods B...
Source: Frontiers in cellular and infection microbiology - April 15, 2019 Category: Microbiology Source Type: research

Oligomeric S100A4 Is Associated With Monocyte Innate Immune Memory and Bypass of Tolerance to Subsequent Stimulation With Lipopolysaccharides
Conclusion: Bypass of tolerance by DAMPs might be a phenomenon as important as TI, since it could explain how chronic inflammation can be maintained in spite of an environment with multiple TLR2/TLR4-ligands. In RA monocytes, a PRDM8-dependent TI mechanism could be responsible for sustained chemokine/cytokines levels. Introduction Monocytes and macrophages play a central role in the pathophysiology of inflammation. For instance, in rheumatoid arthritis (RA), activated monocytes massively infiltrate synovial tissues and produce tumor necrosis factor-α (TNFα) (1–3). Accordingly, therapies aime...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research