Search

Age-related cognitive impairment represents a significant health concern, with the understanding of its underlying mechanisms and potential interventions being of paramount importance. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) on cognitive function and neuronal integrity in aged (22-month-old) C57BL/6 mice. Male mice were exposed to HBOT for 2 weeks, and spatial learning and memory abilities were assessed using the Morris water maze. We employed transcriptome sequencing and Gene Ontology (GO) term enrichment analysis to examine the effects of HBOT on gene expression profiles, with particular attention given to synapse-related genes. Our data indicated a significant upregulation of postsynapse organization, synapse organization, and axonogenesis GO terms, likely contributing to improved cognitive performance. Moreover, the hyperphosphorylation of tau, a hallmark of many neurodegenerative diseases, was significantly reduced in the HBO-treated group, both in vivo and in vitro. Transmission electron microscopy revealed significant ultrastructural alterations in the hippocampus of the HBOT group, including an increase in the number of synapses and the size of the active zone, a reduction in demyelinated lesions, and a decreased number of “PANTHOS.” Furthermore, Western blot analyses confirmed the upregulation of PSD95, BDNF, and Syn proteins, suggesting enhanced synaptic plasticity and neurotrophic support. Moreover, HBOT increased autophagy, as evidenced by the elevated levels of Beclin-1 and LC3 proteins and the reduced level of p62 protein. Finally, we demonstrated that HBOT activated the AMPK-mTOR signaling pathway, a critical regulator of autophagy. Notably, our findings provide novel insights into the mechanisms by which HBOT ameliorates age-related cognitive impairment, suggesting the potential therapeutic value of this approach.

Orthodontic tooth movement (OTM) involves mechanical–biochemical signal transduction, which results in tissue remodeling of the tooth–periodontium complex and the movement of orthodontic teeth. The dynamic regulation of osteogenesis and osteoclastogenesis serves as the biological basis for remodeling of the periodontium, and more importantly, the prerequisite for establishing periodontal homeostasis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key effectors of the Hippo signaling pathway, which actively respond to mechanical stimuli during tooth movement. Specifically, they participate in translating mechanical into biochemical signals, thereby regulating periodontal homeostasis, periodontal remodeling, and tooth development. YAP and TAZ have widely been considered as key factors to prevent dental dysplasia, accelerate orthodontic tooth movement, and shorten treatment time. In this review, we summarize the functions of YAP and TAZ in regulating tooth development and periodontal remodeling, with the aim to gain a better understanding of their mechanisms of action and provide insights into maintaining proper tooth development and establishing a healthy periodontal and alveolar bone environment. Our findings offer novel perspectives and directions for targeted clinical treatments. Moreover, considering the similarities and differences in the development, structure, and physiology between YAP and TAZ, these molecules may exhibit functional variations in specific regulatory processes. Hence, we pay special attention to their distinct roles in specific regulatory functions to gain a comprehensive and profound understanding of their contributions.

Adenosine monophosphate-activated protein kinase (AMPK) is a significant energy sensor in the maintenance of cellular energy homeostasis. Autophagy is a highly conserved catabolic process that involves an intracellular degradation system in which cytoplasmic components, such as protein aggregates, organelles, and other macromolecules, are directed to the lysosome through the self-degradative process to maintain cellular homeostasis. Given the triggered autophagy process in various situations including the nutrient deficit, AMPK is potentially linked with different stages of autophagy. Above all, AMPK increases ULK1 activity by directly phosphorylating Ser467, Ser555, Thr574, and Ser637 at least four sites, which increases the recruitment of autophagy-relevant proteins (ATG proteins) to the membrane domains which affects autophagy at the initiation stage. Secondly, AMPK inhibits VPS34 complexes that do not contain pro-autophagic factors and are thus involved in isolation membrane forming processes, by direct phosphorylation of VPS34 on Thr163 and Ser165. After phosphorylation, AMPK can govern autophagosome formation through recruiting downstream autophagy-related proteins to the autophagosome formation site. Finally, the AMPK-SIRT1 signaling pathway can be activated by upregulating the transcription of autophagy-related genes, thereby enhancing autophagosome-lysosome fusion. This review provides an introduction to the role of AMPK in different stages of autophagy.