Translational research : the journal of laboratory and clinical medicine
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Periodontitis is a chronic inflammatory oral disease that impaired the tooth-supporting apparatus, including gingival tissue destruction and alveolar bone resorption. The initiation of periodontitis is linked to the presence of oral bacteria, particularly P. gingivalis within pathogenic biofilms. Here, we demonstrated the central role of the autophagy regulator Transcription Factor EB (TFEB) in orchestrating autophagy activation and modulating the host immune response against P. gingivalis in periodontitis. ⋯ Functionally, TFEB overexpression emerges as a potent alleviator of periodontitis-associated phenotypes, operating through the activation of autophagy and the inhibition of the NF-κB pathway in both in vivo and in vitro models. In addition, TFEB knockdown exacerbates the inflammatory response by upregulating pro-inflammatory cytokines. The dual regulatory role of TFEB in governing both autophagy and inflammatory responses unveils novel insights into periodontitis pathogenesis, positioning TFEB as a promising therapeutic target for periodontitis intervention.
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Doxorubicin (DOX) is restricted due to its severe cardiotoxicity. There is still a lack of viable and effective drugs to prevent or treat DOX-induced cardiotoxicity(DIC). Vericiguat is widely used to treat heart failure with reduced ejection fraction. ⋯ In the present study, we constructed a DIC model using mice and neonatal rat cardiomyocytes and found that vericiguat ameliorated DOX-induced cardiac insufficiency in mice, restored DOX-induced mitochondrial dysfunction in neonatal rat cardiomyocytes, and inhibited the expression of inflammatory factors. Further studies showed that vericiguat improved mitochondrial dysfunction and reduced mtDNA leakage into the cytoplasm by up-regulating PRKG1, which activated PINK1 and then inhibited the STING/IRF3 pathway to alleviate DIC. These findings demonstrate for the first time that vericiguat has therapeutic potential for the treatment of DIC.