RESUMEN
BACKGROUND: Long non-coding RNAs (LncRNAs) are generally reported to participate in the development of Osteoarthritis (OA) by acting as competing endogenous RNAs (ceRNAs). However, the molecular mechanism is largely unknown. This study aimed to investigate the possible mechanisms contributing to osteoarthritis (OA). METHODS: Four gene expression profiles from patients with OA were downloaded from a public database and integrated to screen important RNAs associated with OA. Differentially expressed (DE) lncRNAs, microRNAs (miRNAs), and mRNAs were filtered, and a ceRNA network was constructed. An in vitro OA model was established by treating chondrocytes with IL-1ß. The expression levels of MMP-13, COL2A1, aggrecan, and RUNX2 were detected by qRT-PCR and western blot. Cell proliferation ability was detected by CCK-8 assay. Flow cytometry was used for apoptosis assay. A dual luciferase reporter gene was used to confirm the relationship between DLEU1, miR-492, and TLR8. RESULTS: An OA-related ceRNA network, including 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs, was constructed. DLEU1 and TLR8 were upregulated, and miR-492 was downregulated in IL-1ß-induced chondrocytes. Overexpression of DLEU1 suppressed viability and promoted apoptosis and extracellular matrix (ECM) degradation in IL-1ß induced chondrocytes. Luciferase reporter assay validated the regulatory relations among DLEU1, miR-492, and TLR8. Further study revealed that the effects of DLEU1 on chondrocytes could be reversed by miR-492. CONCLUSION: DLEU1 may be responsible for the viability, apoptosis, and ECM degradation in OA via miR-492/TLR8 axis.
RESUMEN
BACKGROUND: Vitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis. METHODS: The serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis. RESULTS: In the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas. CONCLUSION: Sepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.