Energy metabolism as therapeutic target for aged wound repair by engineered extracellular vesicle.

Aging skin, vulnerable to age-related defects, is poor in wound repair. Metabolic regulation in accumulated senescent cells (SnCs) with aging is essential for tissue homeostasis, and adequate ATP is important in cell activation for aged tissue repair. Strategies for ATP metabolism intervention hold prospects for therapeutic advances. Here, we found energy metabolic changes in aging skin from patients and mice. Our data show that metformin engineered EV (Met-EV) can enhance aged mouse skin repair, as well as ameliorate cellular senescence and restore cell dysfunctions. Notably, ATP metabolism was remodeled as reduced glycolysis and enhanced OXPHOS after Met-EV treatment. We show Met-EV rescue senescence-induced mitochondria dysfunctions and mitophagy suppressions, indicating the role of Met-EV in remodeling mitochondrial functions via mitophagy for adequate ATP production in aged tissue repair. Our results reveal the mechanism for SnCs rejuvenation by EV and suggest the disturbed energy metabolism, essential in age-related defects, to be a potential therapeutic target for facilitating aged tissue repair.

[Morphological changes of upper airway in patients with skeletal Class â ¢ malocclusion after bimaxillary surgery and correlation analysis].

PURPOSE: To analyze the morphological changes of the upper airway and related influencing factors in patients with skeletal Class Ⅲ malocclusion after bimaxillary surgery. METHODS: Twenty skeletal Class Ⅲ patients who underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy(BSSRO) for maxillary advancement and mandibular setback were selected. The patients received CT scans before(T0) and 3-6 months after surgery, and the images were reconstructed three-dimensionally with Dolphin Imaging 11.9 software. Changes in the volume, cross-sectional area, and landmarks of each soft and hard tissue of the airway were measured. Statistical analysis of the data was performed using SPSS 25.0 software package. RESULTS: The volume of nasopharyngeal airway increased after operation (P＜0.05), and the volume of oropharyngeal airway decreased significantly(P＜0.01). The cross-sectional area of the airway at the plane of the second cervical vertebra was significantly decreased (P＜0.01), and the coronal and sagittal diameters were decreased(P＜0.05). The change of nasopharyngeal airway volume was moderately positively correlated with the sagittal change of the posterior nasal spine (r=0.460, P＜0.05), and the change of oropharynx and laryngopharyngeal airway volume was positively correlated with the vertical change of the midpoint of the soft palate(r=0.496, 0.696, P＜0.05). The airway cross-sectional area in the second and third cervical vertebra planes and the sagittal diameter of the airway in the third cervical vertebra plane were positively correlated with the vertical changes of the midpoint of the soft palate(r=0.474, 0.629, 0.547, P＜0.05). The change of airway cross-sectional area at the third cervical vertebra plane was moderately negatively correlated with the change of mandibular plane angle(r=-0.536, P＜0.05). CONCLUSIONS: The volume and cross-sectional area of oropharyngeal airway in skeletal Class Ⅲ patients after bimaxillary surgery will decrease. However, the total upper airway volume doesn't change significantly. The changes in the upper airway are correlated with the changes in some soft and hard tissue landmarks.

Transcriptomic analysis provides a new insight: Oleuropein reverses high glucose-induced osteogenic inhibition in bone marrow mesenchymal stem cells via Wnt10b activation.

Adverse events of diabetes mellitus (DM) include bone damages, such as the increased incidence of osteoporosis and bone fractures, which are known as diabetic osteopathy. The pathogenic mechanism of diabetic osteopathy is complex, and hyperglycemia is a vital cause involved in it. Bone marrow mesenchymal stem cells (BMSCs) exert a significant effect on bone formation. Therefore, in this paper, transcriptomic changes of BMSCs cultured in high glucose (35 mM) for 30 days are mainly investigated. In addition, 794 up-regulated genes and 1,162 down-regulated genes were identified. Then, biological functions of the differentially expressed genes in the high glucose microenvironment were investigated by two kinds of functional analyses. Gene Set Enrichment Analysis was also applied to focus on the significant gene sets and it is found that Wnt10b expression witnessed a remarkable decrease in BMSCs under the high glucose microenvironment. At last, in vitro experiments revealed that oleuropein effectively reversed high glucose-induced osteogenic inhibition via activating Wnt10b in BMSCs.