Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia

Elevated fibroblast growth factor 23(FGF23)in X-linked hypophosphatemia(XLH)results in rickets and phosphate wasting,manifesting by severe bone and dental abnormalities.Burosumab,a FGF23-neutralizing antibody,an alternative to conventional treatment(phosphorus and active vitamin D analogs),showed significant improvement in the long bone phenotype.Here,we examined whether FGF23 antibody(FGF23-mAb)also improved the dentoalveolar features associated with XLH.Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type(WT)and vehicle(PBS)treated Hyp mice(n=3–7 mice).Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice,the higher concentration resulting in a rescue similar to WT levels.FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones.Histology revealed improved mineralization of the dentoalveolar tissues,with a decreased amount of osteoid,predentin and cementoid.Better periodontal ligament attachment was also observed,evidenced by restoration of the acellular cementum.These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features.Taken together,our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment,heralding its benefit in clinics for dental abnormalities.

Effects of lysedEnterococcus faecalis FK-23 on experimental allergic rhinitis in a murine model

In the current study, we sought to investigate whether lysed Enterococcus faecalis FK-23 （LFK）, a heat-killed probiotic preparation, attenuated eosinophil influx into the upper airway and had immunomodulatory activity in a murine allergic rhinitis model. Eighteen BALB/c mice were divided into three groups; the ovalbumin （OVA）-sen- sitized/challenged group, which received saline orally for 6 weeks （OVA group）, the OVA-sensitized/challenged group, which received LFK orally for 6 weeks （LFK-fed group）, and the non-sensitized group, which received saline for 6 weeks （saline control group）. Nasal rubbing and sneezing were monitored during the study. After the final challenge, interleukin （IL）-4, interferon （IFN）-y, and OVA-specific IgE levels in the sera and splenocyte culture supernatants were determined, eosinophilic infiltrate into the upper airway was quantified, and splenic CD4~CD25＋ regulatory T cells （Tregs） were examined by flow cytometry. We found that nasal rubbing was sig- nificantly reduced in LFK-fed mice compared to the OVA group on d 27 and 35, and sneezing was significantly inhibited by LFK administration for 35 d. LFK-fed mice had significantly less eosinophil influx into the nasal mucosa than the OVA group. There were no significant differences between the LFK-fed group and OVA group in the serum and splenocyte culture supernatant levels of IL-4, IFN-y, and OVA-specific IgE. Interestingly, the LFK-fed mice had a significantly greater percentage of splenic CD4＋CD25＋ Tregs than OVA group. Our results indicate that oral administration of LFK may alleviate nasal symptoms, reduce nasal eosinophilia, and increase the percentage of CD4＋CD25＋ Tregs in experimental allergic rhinitis.

Immunomodulation effects of heat-treated Enterococcus faecalis FK-23(FK-23) in mice

Objective：The purpose of this study was to evaluate the effects of Enterococcusfaecalis FK-23（FK-23） on the immune function in mice. Methods：Mice were treated with three doses of the FK-23（0.05, 0.1, 0.2, 0.6 g/kg body weight） for 30 days. Delayed type hypersensitivity （DTH）, monocyte phagocytic function, serum hemolysis antibody and natural killer cell activity were studied. Results： The significant increases in mice treated with 0.6 g/kg bw were found in DTH, phagocytic function of monocyte, serum hemolysis antibody and natural killer cell activity. Conclusion：The results from the present study suggest that FK-23 could improve both specific and nonspecific immune function.

Gas Absorption by Wavy Falling Liquid Film Formed on Inner Surface of Vertical lubes

An experimental study on gas absorption into falling liquid film formed on inner surface of vertical tubes has been carried out in order to clarify fundamental characteristics of the gas absorption and enhancement by surface waves. The water supplied into the test tubes is periodically disturbed by fluctuating a silicon tube before the test section with a speaker and the wavy films absorb the oxygen filled in the tubes. Imposing the periodic disturbance enhances the gas absorption and the enhancement has a maximum at around 20-30 Hz, where the gas absorption is 20-30% higher. Mass transfer coefficients obtained with five tubes agree well with those obtained with single tube. Two-dimensional numerical simulations have also been conducted for gas absorption by wavy film and the enhancement mechanism of the gas absorption is discussed.