International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 126741 - 126741
Published: Sept. 10, 2023
Language: Английский
Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9
Published: Nov. 16, 2022
Objective The pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript has close associations with multiple diseases. This study aimed to investigate role m6A in patients pSS. Materials and methods enrolled 44 pSS, 50 age- gender-matched healthy controls (HCs), 11 non-SS sicca. We detected messenger (mRNA) levels elements (including METTL3, WTAP, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2), ISG15, USP18 peripheral blood mononuclear cells (PBMCs) from sicca, HCs. clinical characteristics laboratory findings pSS sicca were also collected. used binary logistic regression determine if risk factors for Results mRNA writers (METTL3 RBM15), erasers (ALKBH5 FTO), readers (YTHDF1, YTHDC2) all significantly higher PBMCs than WTAP) (YTHDF2, lower compared expression YTHDC2 was positively correlated level C-reactive protein (CRP) YTHDF1 negatively EULAR disease activity index (ESSDAI) score. In related white (WBCs), neutrophils, lymphocytes, monocytes. Increased ALKBH5 a factor as determined by analysis. ISG15 that Conclusion Compared HCs, considerably comparison reduced correlating variables may indicate inflammation status Elevated dynamic process modification is active (FTO, or might target stimulate activate type I IFN signaling pathway, playing an initiating autoimmunity
Language: Английский
Citations
10
Investigative Ophthalmology & Visual Science, Journal Year: 2022, Volume and Issue: 63(10), P. 20 - 20
Published: Sept. 28, 2022
Our previous investigations revealed a significant role of methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification in the development corneal inflammation Fusarium infection, but exact mechanism is unknown. Therefore, this research aimed to explore how METTL3 affects inflammatory process fungal keratitis (FK) mice.We established vitro and vivo models by inoculating mice primary stromal cells with F. solani. expression was confirmed real-time quantitative polymerase chain reaction, immunofluorescence, western blotting. After that, siRNAMETTL3 AAV-sh-METTL3 were transfected into PI3K/AKT signaling pathway inflammation. PI3K, p-PI3K, AKT, p-AKT analyzed Viability measured using Cell Counting Kit-8 (CCK-8). Additionally, we detected interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α) levels tissues FK slit-lamp biomicroscopy hematoxylin eosin staining.Here, our results show that increased mouse FK, p-PI3K decreased when downregulated. We also found knockdown attenuated response TNF-α, IL-6 corneal-infected mice. Furthermore, inhibition above factors, enhanced viability cells.Based on study results, downregulation attenuates Fusarium-induced via pathway.
Language: Английский
Citations
9
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Aug. 10, 2023
Introduction Human cytomegalovirus (HCMV) infection in infants can lead to severe diseases, including neonatal hepatitis. The single-cell dimensional changes immune cells after the initial CMV remain elusive, as do effects of on hepatic lipid metabolism. Methods We employed RNA-sequencing investigate liver cell types and responses infant mice following murine (MCMV) infection. Additionally, we examined alterations protein expression profiles related metabolism hepatocytes role key transcription factor PPAR-γ during Results Our study revealed that MCMV infects most mice, leading an increase proportion proliferating CD8 effector T a subset Nos2 + monocytes, potentially playing essential early anti-viral responses. Furthermore, resulted altered hepatocytes. Knocking down effectively inhibited Discussion findings underscore system's response early-stage subsequent impact mice. This research provides new insights into mechanisms could pave way for novel therapeutic strategies.
Language: Английский
Citations
5
Investigative Ophthalmology & Visual Science, Journal Year: 2022, Volume and Issue: 63(11), P. 2 - 2
Published: Oct. 4, 2022
Purpose: The purpose of this study was to elucidate the effect methyltransferase-like enzyme 3 (METTL3) on inflammation and NF-κB signaling pathway in fungal keratitis (FK). Methods: We established corneal stromal cell models FK mouse by incubation with Fusarium solani. overall RNA N6-methyladenosine (m6A) level determined using an m6A methylation assay kit. expression METTL3 quantified via real-time quantitative polymerase chain reaction (RT–PCR), Western blotting, immunofluorescence. Subsequently, tumor necrosis factor (TNF) receptor-associated 6 (TRAF6) identified blotting Moreover, we assessed transfecting cells siRNA (in vitro) or adeno-associated virus vivo). Hematoxylin eosin (H&E) staining slit-lamp biomicroscopy were performed evaluate damage. Furthermore, state activation examined blotting. In addition, RT–PCR enzyme-linked immunosorbent assays (ELISAs) levels pro-inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6) TNF-ɑ. Results: Our data demonstrated that dramatically increased activated solani-induced keratitis. Inhibition decreased TRAF6, downregulated phospho-p65(p-p65)/p65 phospho-IκB(p-IκB)/IκB protein ratios, simultaneously attenuating inflammatory response burden FK. Conclusions: research suggests methyltransferase regulates modulating pathway.
Language: Английский
Citations
8
International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 126741 - 126741
Published: Sept. 10, 2023
Language: Английский
Citations
4