Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.
Background Syphilis is a bacterial STI caused by Treponema pallidum that results in substantial morbidity and mortality. Currently, it has been suggested that exosomes (Exo) may play a possible role as novel biomarkers for the detection of infectious diseases. Here, we investigated the exosomal miRNA derived from plasma in syphilis, aimed to help in the diagnosis and prognosis of serofast syphilis. Methods A discovery cohort was used to investigate exosomal miRNAs that vary across the different subjects of participants. Exosomal miRNAs were isolated from peripheral plasma obtained at secondary syphilis(SS,n=5), serofast(SF,n=6),healthy control(HC,n=5) and serologically cured syphilis patients(SC,n=4), and microarray analysis was performed. A validation cohort was used to confirm the selected differential expression of exosomal miRNAs by real-time fluorescence quantitative PCR (RT-qPCR). ROC analysis was used to evaluate the differentiation power of these miRNAs in syphilis diagnosis. Results The microarray result revealed a specific plasma exosomal miRNA expression profile in serofast syphilis. 44 miRNAs showed significant differences between serofast and secondary syphilis, and 12 miRNAs were differentially expressed between serofast and serologically cured syphilis patients. MiR-1273g-3p, miR-4485-5p, miR-197-3p, miR- 1908-3p were significantly upregulated in syphilis patients in a stage-specific manner. These miRNAs singly or jointly displayed an improved diagnostic capability to differentiate serological cure patients or healthy people from serofast syphilis. Conclusions In practical work, differently-expressed exosomal miRNAs may be of great clinical significant utility in the diagnosis and prognosis of serofast syphilis. According to the data, miR-197-3p, miR- 1908-3p, miR-1273g-3p, miR-4485-5p within exosomes might singly or jointly be potential diagnostic biomarkers at serofast syphilis.
Purpose Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum (T. pallidum) , which can lead to chronic morbidity and adverse complications. In clinical practice, serofast status (SF) patients present with clinical symptoms that are very similar to those of healthy individuals or syphilis-cured patients, and often require prolonged follow-up for diagnosis. Currently, there is increasing interest in the potential of plasma exosome-derived miRNA as a biomarker for the detection of infectious diseases. In this study, we aimed to explore the diagnostic potential of miRNA in SF and its possible biological implications. Patients and Methods Exosome-derived miRNAs were isolated from peripheral plasma samples obtained from 20 patients with secondary syphilis (SS), SF, serologically cured syphilis (SC), and healthy controls (HC), and differentially expressed miRNAs (DEmiRNAs) were identified by microarray analysis. Prediction of potential target genes, functional annotation, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then performed. The expression of selected miRNAs was confirmed in 37 patients by quantitative reverse transcription polymerase chain reaction (RT-qPCR). A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of these miRNAs in differentiating syphilis from HC or SC. Results The expression profile of plasma exosome-derived miRNA was discovered in individuals with SF through microarray analysis. The targeted genes of DEmiRNAs were found to be involved in diverse biological processes according to GO and KEGG analysis, such as regulation of transcription, mitochondria, Golgi, immune system, apoptosis, Ras signaling pathway, etc. Using RT-qPCR validation, miR-1273g-3p, miR-4485-5p, miR-197-3p, and miR-1908-3p showed significant upregulation in patients with SF. These miRNAs exhibited a superior diagnostic ability, either individually or combined, to distinguish SF from SC or HC. Conclusion The DEmiRNAs in plasma exosomes may play a role in the pathogenesis of SF and have the potential to become a noble and effective diagnostic method.
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