Formation of the junctions between lymph follicles in the Peyer's patches even before postweaning activation.

Peyer's patches (PPs), which contain an abundance of B and T cells, play a key role in inducing pivotal immune responses in the intestinal tract. PPs are defined as aggregated lymph follicles, which consist of multiple lymph follicles (LFs) that may interact with each other in a synergistic manner. LFs are thought to be spherical in shape; however, the characteristics of their structure are not fully understood. To elucidate changes in the structure of PPs as individuals grow, we generated serial 2D sections from entire PPs harvested from mice at 2, 4, and 10 weeks of age and performed a 3D analysis using a software, Amira. Although the number of LFs in PPs was not changed throughout the experiment, the volume and surface area of LFs increased significantly, indicating that LFs in PPs develop continuously by recruiting immune cells, even after weaning. In response to the dramatic changes in the intestinal environment after weaning, the development of germinal centers (GCs) in LFs was observed at 4 and 10 weeks (but not 2 weeks) of age. In addition, GCs gradually began to form away from the center of LFs and close to the muscle layer where export lymphatic vessels develop. Importantly, each LF was joined to the adjacent LF; this feature was observed even in preweaning nonactivated PPs. These results suggest that PPs may have a unique organization and structure that enhance immune functions, allowing cells in LFs to have free access to adjacent LFs and egress smoothly from PPs to the periphery upon stimulation after weaning.

Highly purified hypochlorous acid water facilitates glucose metabolism and memory formation in type 2 diabetic mice associated with altered-gut microbiota.

Hypochlorous acid (HOCl) is an endogenous oxidant and chlorinating agent in mammals that is effective against a broad range of microorganisms. However, the effects of exogenous HOCl on biological processes have not been reported. In this study, the effects of highly purified slightly acidic hypochlorous acid water (HP-HAW) were investigated. After the safety of oral administration of HP-HAW was confirmed, the effects of HP-HAW on glucose homeostasis were assessed in mice. HP-HAW treatment significantly improved blood glucose levels in hyperglycemic condition. Based on the 16S rRNA sequencing, HP-HAW treatment significantly increased the diversity and changed the composition of gut microbiota by decreasing the abundance of genus Romboutsia in mice fed normal chow. In obese mice, HP-HAW administration tended to improve glucose tolerance. HP-HAW also attenuated memory impairments and changes N-methyl-d-aspartate (NMDA) receptor mRNA expression in obese mice. HP-HAW treatment suppressed Il-6 mRNA expression in the hippocampus in type 2 diabetic mice. Overall, these results support HP-HAW as a potential therapeutic agent to improve or prevent glucose tolerance and memory decline via gut microbiota alteration.

Effect of age on orthodontic tooth movement in mice.

Background/purpose: The number of middle-aged and elderly orthodontic patients is increasing due to changes in age composition. It is important to investigate the detailed mechanisms of bone remodeling in orthodontic tooth movement (OTM) in the elderly. However, there are few reports on the mechanism of tooth movement in the elderly. The purpose of the present study was to analyze OTM and osteoclastogenesis in aged mice and to elucidate the mechanism. Materials and methods: It has been reported that tumor necrosis factor (TNF)-α plays an important role in osteoclast formation and OTM. First, 8-week-old and 78-week-old male C57BL/6J mice were subcutaneously injected with TNF-α into the calvaiae, and micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, and real-time PCR were performed to evaluate osteoclast formation and bone resorption. Furthermore, osteoclastogenesis by TNF-α and receptor activator of nuclear factor-kappa B ligand (RANKL) using bone marrow cells was evaluated in vitro. Finally, a nickel-titanium closed-coil spring was attached, mesial movement of the maxillary left first molar was performed, and tooth movement distance and osteoclast formation were evaluated. Results: Compared to 8-week-old mice, 78-week-old mice had decreased TNF-α-induced bone resorption, osteoclastogenesis, and TRAP and cathepsin K expression in the calvariae. In vitro osteoclast formation also decreased in 78-week-old mice. Furthermore, tooth movement distance and osteoclastogenesis were reduced. Conclusion: OTM decreased in aged mice, which was shown to be caused by a decrease in osteoclastogenesis. Therefore, it was suggested that it is necessary to keep in mind that tooth movement may be suppressed when treating elderly patients.