ABSTRACT
BACKGROUND: Osteoarthritis (OA) represents a prominent etiology of considerable pain and disability, and conventional imaging methods lack sensitivity in diagnosing certain types of OA. Therefore, there is a need to identify highly sensitive and efficient biomarkers for OA diagnosis. Zinc ions feature in the pathogenesis of OA. This work aimed to investugate the role of zinc metabolism-related genes (ZMRGs) in OA and the diagnostic characteristics of key genes. METHODS: We obtained datasets GSE169077 and GSE55235 from the Gene Expression Omnibus (GEO) and obtained ZMRGs from MSigDB. Differential expression analysis was conducted on the GSE169077 dataset using the limma R package to identify differentially expressed genes (DEGs), and the intersection of DEGs and ZMRGs yielded zinc metabolism differential expression-related genes (ZMRGs-DEGs). The clusterProfiler R package was employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of ZMRGs-DEGs. Potential small molecule drugs were predicted using the CMap database, and immune cell infiltration and function in OA individuals were analyzed using the ssGSEA method. Protein-protein interaction (PPI) networks were constructed to detect Hub genes among ZMRGs-DEGs. Hub gene expression levels were analyzed in the GSE169077 and GSE55235 datasets, and their diagnostic characteristics were assessed using receiver operating characteristic (ROC) curves. The gene-miRNA interaction network of Hub genes was explored using the gene-miRNA interaction network website. RESULTS: We identified 842 DEGs in the GSE169077 dataset, and their intersection with ZMRGs resulted in 46 ZMRGs-DEGs. ZMRGs-DEGs were primarily enriched in functions such as collagen catabolic processes, extracellular matrix organization, metallopeptidase activity, and pathways like the IL-17 signaling pathway, Nitrogen metabolism, and Relaxin signaling pathway. Ten potential small-molecule drugs were predicted using the CMap database. OA patients exhibited distinct immune cell abundance and function compared to healthy individuals. We identified 4 Hub genes (MMP2, MMP3, MMP9, MMP13) through the PPI network, which were highly expressed in OA and demonstrated good diagnostic performance. Furthermore, two closely related miRNAs for each of the 4 Hub genes were identified. CONCLUSION: 4 Hub genes were identified as potential diagnostic biomarkers and therapeutic targets for OA.
Subject(s)
MicroRNAs , Zinc , Humans , Proteolysis , Databases, Factual , Biomarkers , Computational Biology , Gene Expression ProfilingABSTRACT
Candida albicans is one of the most common species of Candida, which cause various mucosal and systemic infectious diseases. However, the resistance rate to existing clinical antifungal drugs gradually increases in C. albicans. Therefore, new antifungal drugs must be developed to solve the current problem. This study discovered that the solid fermented ethyl acetate crude extract of Microporus vernicipes had inhibitory activity on C. albicans. This study determined that the Mv5 components had significantly inhibited the activity of C. albicans using column chromatography separation component screening. The components included 23 compounds of fatty acids and their derivatives, alkaloids, phenols, and other classes using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HR-MS) analysis, with fatty acids constituting the primary components. The mechanism of action showed that the minimum inhibitory concentration (MIC) of Mv5 components against C. albicans was 15.63 µg/mL, while minimum fungicidal concentration (MFC) was 31.25 µg/mL. Mv5 components can inhibit the early biofilm formation and destroy the mature biofilm structure. It can inhibit the germ tube growth of C. albicans, thereby inhibiting the transformation of yeast morphology to hyphae. We detected 193 differentially expressed genes, including 156 upregulated and 37 downregulated genes in the Mv5 components of the MIC concentration group. We detected 391 differentially expressed genes, including 334 upregulated and 57 downregulated expression genes in the MFC concentration group. Among these differentially expressed genes, the genes related to mycelium and biofilm formation were significantly downregulated. GO enrichment analysis presented that single-organism process metabolic process, and cellular processes were the biological processes with the most gene enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG)of Mv5 components were mainly enriched in metabolic pathways, such as meiosis yeast and amino acid metabolism. Therefore, it is believed that the fermentation extract of M. vernicipes inhibits C. albicans, which can provide clues for developing effective antifungal drugs.
ABSTRACT
Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1ß treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1ß treatment promoted inflammatory factor secretion in chondrocytes, promoted cell apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1ß effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1ß-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1ß-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1ß induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression.
