Amyloid precursor protein (APP) has an important function in the generation of Alzheimer's disease (AD). In our previous study, miR‑193b was found to be downregulated in the hippocampi of 9‑month‑old APP/PS1 double‑transgenic mice using microRNA (miR) array. In the present study, bioinformatic analyses showed that miR‑193b was a miR that was predicted to potentially target the 3'‑untranslated region (UTR) of APP. Subsequently, the function of miR‑193b on APP was studied. The levels of miR‑193b, exosomal miR‑193b, Aβ, tau, p‑tau, HCY and APOE in samples from APP/PS1 double‑transgenic mice, mild cognitive impairment (MCI) and dementia of Alzheimer‑type (DAT) patients, were measured. The results indicated that overexpression of miR‑193b could repress the mRNA and protein expression of APP. The miR‑193b inhibitor oligonucleotide induced upregulation of APP. Binding sites of miR‑193b in the 3'‑UTR of APP were identified by luciferase assay. MCI and DAT patients had lower exosomal miR‑193b, but not total miR‑193b, in the blood as compared with the controls. DAT patients had lower exosomal miR‑193b levels in blood as compared with the MCI group. A decreased exosomal miR‑193b expression level was additionally observed in the cerebral spinal fluid (CSF) of DAT patients. Negative correlations were found between exosomal miR‑193b and Aβ42 in the CSF of DAT patients. In conclusion, these findings showed that miR‑193b may function in the development of AD and exosomal miR‑193b has potential as a novel, non-invasive, blood‑based biomarker of MCI and DAT patients.

Owing to the growing infectious diseases caused by eukaryotic and prokaryotic pathogens, it is urgent to develop novel antimicrobial agents against clinical pathogenic infections. Biofilm formation and invasion into the host cells are vital processes during pathogenic colonization and infection. In this study, we tested the inhibitory effect of Au nanoparticles (AuNPs) on pathogenic growth, biofilm formation and invasion. Interestingly, although the synthesized AuNPs had no significant toxicity to the tested pathogens, Candida albicans and Pseudomonas aeruginosa, the nanoparticles strongly inhibited pathogenic biofilm formation and invasion to dental pulp stem cells (DPSCs). Further investigations revealed that AuNPs abundantly bound to the pathogen cells, which likely contributed to their inhibitory effect on biofilm formation and invasion. Moreover, treatment of AuNPs led to activation of immune response-related genes in DPSCs, which may enhance the activity of host immune system against the pathogens. Zeta potential analysis and polyethylene glycol (PEG)/polyethyleneimine (PEI) coating tests further showed that the interaction between pathogen cells and AuNPs is associated with electrostatic attractions. Our findings shed novel light on the application of nanomaterials in fighting against clinical pathogens, and imply that the traditional growth inhibition test is not the only way to evaluate the drug effect during the screening of antimicrobial agents.

Mitochondrial damage is involved in the pathogenesis of osteoarthritis. Metformin, one of the most common prescriptions for patients with type 2 diabetes, can reportedly activate Sirtuin 3 (SIRT3) expression which protects mitochondria from oxidative stress. In this study, we investigated the inhibitory property of metformin on mitochondrial damage by focusing on the interleukin-1 beta (IL-1β)-stimulated osteoarthritis model by using primary murine chondrocytes. Our results demonstrated that SIRT3 was downregulated in chondrocytes under IL-1β stimulation, where its expression was positively correlated with mitochondrial damage and reactive oxygen species (ROS) production. Metformin treatment upregulated SIRT3 expression and mitigated loss of cell viability and decreased the generation of mitochondria-induced ROS in chondrocytes stimulated with IL-1β. Metformin also attenuated IL-1β-induced expressions of catabolic genes such as matrix metalloproteinase-3 (MMP3) and MMP13 and enhanced the anabolic indicator Collagen Ⅱ. These effects were mediated by phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1)/Parkindependent mitophagy and the autophagic elimination of damaged mitochondria. Further, the SIRT3 inhibitor 3-TYP effectively inhibited the initiation of mitophagy, as decreased expression of PINK1 and Parkin, decreased the LC3II/LC3I, enhanced the expression of MMP3 and MMP13, and decreased the expression of Collagen Ⅱ. Overall, our findings provide evidence that metformin suppresses IL-1β-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin's potential in prevention and treatment of osteoarthritic joint disease.