Acinetobacter baumannii
resistance to carbapenem antibiotics is a serious clinical challenge. As a newly developed technology, silver nanoparticles (AgNPs) show some excellent characteristics compared to older treatments, and are a candidate for combating
A. baumannii
infection. However, its mechanism of action remains unclear. In this study, we combined AgNPs with antibiotics to treat carbapenem-resistant
A. baumannii
(aba1604). Our results showed that single AgNPs completely inhibited
A. baumannii
growth at 2.5 μg/mL. AgNP treatment also showed synergistic effects with the antibiotics polymixin B and rifampicin, and an additive effect with tigecyline. In vivo, we found that AgNPs–antibiotic combinations led to better survival ratios in
A. baumannii
-infected mouse peritonitis models than that by single drug treatment. Finally, we employed different antisense RNA-targeted
Escherichia coli
strains to elucidate the synergistic mechanism involved in bacterial responses to AgNPs and antibiotics.
Background
Human Schlafen 5 (SLFN5) has been reported to inhibit or promote cell invasion in tumours depending on their origin. However, its role in breast cancer (BRCA) is undetermined.
Methods
Differential expression analyses using The Cancer Genome Atlas (TCGA) data, clinical samples and cell lines were performed. Lentiviral knockdown and overexpression experiments were performed to detect changes in cell morphology, molecular markers and invasion. Chromatin immunoprecipitation-sequencing (ChIP-Seq) and luciferase reporter assays were performed to detect the SLFN5-binding motif.
Results
TCGA, clinical samples and cell lines showed that SLFN5 expression was negatively correlated with BRCA metastasis. SLFN5 knockdown induced epithelial–mesenchymal transition (EMT) and enhanced invasion in BRCA cell lines. However, overexpression triggered mesenchymal–epithelial transition (MET). SLFN5 inhibited the expression of ZEB1 but not ZEB2, SNAI1, SNAI2, TWIST1 or TWIST2. Knockdown and overexpression of ZEB1 indicated that it was a mediator of the SLFN5-governed phenotype and invasion changes. Moreover, SLFN5 inhibited
ZEB1
transcription by directly binding to the SLFN5-binding motif on the
ZEB1
promoter, but a SLFN5 C-terminal deletion mutant did not.
Conclusion
SLFN5 regulates reversible epithelial and mesenchymal transitions, and inhibits BRCA metastasis by suppression of
ZEB1
transcription, suggesting that SLFN5 could be a potential target for BRCA therapy.
Methylglyoxal (MG) is a reactive dicarbonyl compound, whose abnormal accumulation in diabetic patients exerts deleterious effects on cells and tissues. The β-cell is the main target cell of Type 2 diabetes, and its insulin secretion injury and cell apoptosis can be due to mitochondrial dysfunction. Previous studies have demonstrated MG induced β-cell apoptosis. However, little is known about the effect of MG on β-cell mitochondrial dysfunction. Phycocyanin (PC) has been demonstrated to possess various biological activities including the effects on diabetic models in vivo. The aim of this study was to determine the protective effect of PC against methylglyoxal (MG)-induced dysfunction in pancreatic β-cell INS-1 and also the mechanism. We demonstrated that MG induced mitochondrial dysfunction by the decline in ATP levels, and the increase of the level of intracellular reactive oxygen species (ROS). Furthermore, MG released cytochrome c and apoptosis-inducing factor (AIF) from the mitochondrion, induced changes in the expression of Bcl-2 family members, activated caspases and increased PARP cleavage. Interestingly, PC activated nuclear erythroid-related factor 2 (Nrf2), and Nrf2 activation as well as antioxidant enzymes HO-1 and glyoxalase 1 (Glo-1) were confirmed to be involved in the mechanisms underlying the protection of PC by RNA interference. Altogether, these results demonstrated that PC prevented mitochondrial-dependent apoptosis in MG-induced INS-1 cells and the effect was associated with Nrf2 activation.
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