Porphyromonas gingivalis OMVs promoting endothelial dysfunction via the STING pathway in periodontitis.

OBJECTIVE: This study aimed to assess the effects of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs) in chronic periodontitis and explore the underlying mechanism involved. METHODS: In vitro, Pg-OMVs were incubated with Ea.hy926 (vessel endothelial cells, ECs) to evaluate their effects on endothelial functions and to investigate the underlying mechanism. The effects of endothelial dysfunction on MG63 osteoblast-like cells were verified using an indirect co-culture method. For in vivo studies, micro-CT was conducted to identify alveolar bone mass. Immunofluorescence staining was conducted to confirm the levels of stimulator of interferon genes (STING) in the blood vessel and the number of Runx2+ cells around the alveolar bone. RESULTS: Pg-OMVs were endocytosed by ECs, leading to endothelial dysfunction. The cGAS-STING-TBK1 pathway was activated in ECs, which subsequently inhibited MG63 migration and early osteogenesis differentiation. In vivo, Pg-OMVs promoted alveolar bone resorption, increased STING levels in the blood vessel, and decreased Runx2+ cells around the alveolar bone. CONCLUSIONS: Pg-OMVs caused endothelial dysfunction and activated the cGAS-STING-TBK1 signal cascade in ECs, thereby impairing ECs-mediated osteogenesis. Furthermore, Pg-OMVs aggregated alveolar bone loss and altered the blood vessel-mediated osteogenesis with elevated STING.

Frontiers and hotspots in hand, foot, and mouth disease research during 2006 to 2023: A bibliometric and visual analysis.

BACKGROUND: Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD. METHODS: Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package "Bibiometrix," SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data. RESULTS: A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research. CONCLUSION: By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.

Au/Doc/Quer@PDA/A10-3.2 Nanoparticles for targeted treatment of docetaxel-resistant prostate cancer.

Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC.

Three-dimensional evaluation of the mandibular condyle in adults with various skeletal patterns.

Objective: Morphometric and morphological evaluation of the mandibular condyle in adults and to identify its correlation with skeletal malocclusion patterns. Methods: Cone-beam computed tomography scans of 135 adult patients were used in this study and classified into groups according to four criteria: (1) sex (male and female); (2) sagittal skeletal discrepancy (Class I, Class II, and Class III); (3) vertical skeletal discrepancy (hyperdivergent, normodivergent, and hypodivergent); and age (group 1 ≤ 20 years, 21 ≤ group 2 < 30, and group 3 ≥ 30 years). The morphometrical variables were mandibular condyle height and width, and the morphological variable was the mandibular condyle shape in coronal and sagittal sections. Three-dimensional standard tessellation language files were created using itk-snap (open-source software), and measurements were performed using Meshmixer (open-source software). Results: The mandibular condyle height was significantly greater (p < 0.05) in patients with class III malocclusion than in those with class I or II malocclusion; the mandibular condyle width was not significantly different among different sexes, age groups, and sagittal and vertical malocclusions. There were no statistical associations between various mandibular condyle shapes and the sexes, age groups, and skeletal malocclusions. Conclusions: The condylar height was greatest in patients with class III malocclusion. The condylar height and width were greater among males than in females. The mandibular condyle shapes observed in sagittal and coronal sections did not affect the skeletal malocclusion patterns.