Kamebakaurin Suppresses Antigen-Induced Mast Cell Activation by Inhibition of FcεRI Signaling Pathway.

INTRODUCTION: Kamebakaurin is an active constituent of both Rabdosia japonica and Rabdosia excisa, which are utilized in Chinese traditional medicine for improving symptoms in patients with allergies. We investigated the molecular mechanisms of the anti-allergic effects of kamebakaurin using BMMCs. METHODS: The degranulation ratio, histamine release, and the interleukin (IL)-4, leukotriene B4 (LTB4), and cysteinyl leukotriene productions on antigen-triggered BMMC were investigated. Additionally, the effects of kamebakaurin on signal transduction proteins were examined by Western blot and binding to the Syk and Lyn kinase domain was calculated. The effects of kamebakaurin on antigen-induced hyperpermeability were investigated using mouse model. RESULTS: At 10 µm, kamebakaurin partially inhibited degranulation, histamine release, and IL-4 production. At 30 µm, kamebakaurin partially reduced LTB4 and cysteinyl leukotriene productions and suppressed degranulation, histamine release, and IL-4 production. Phosphorylation of both Syk Y519/520 and its downstream protein, Gab2, was reduced by kamebakaurin, and complete inhibition was observed with 30 µm kamebakaurin. In contrast, phosphorylation of Erk was only partially inhibited, even in the presence of 30 µm kamebakaurin. Syk Y519/520 is known to be auto-phosphorylated via intramolecular ATP present in its own ATP-binding site, and this auto-phosphorylation triggers degranulation, histamine release, and IL-4 production. Docking simulation study indicated kamebakaurin blocked ATP binding to the ATP-binding site in Syk. Therefore, inhibition of Syk auto-phosphorylation by kamebakaurin binding to the Syk ATP-binding site appeared to cause a reduction of histamine release and IL-4 production. Kamebakaurin inhibited antigen-induced vascular hyperpermeability in a dose-dependent fashion but did not reduce histamine-induced vascular hyperpermeability. CONCLUSION: Kamebakaurin ameliorates allergic symptoms via inhibition of Syk phosphorylation; thus, kamebakaurin could be a lead compound for the new anti-allergic drug.

[Perceptual changes among public health nurses brought on through a newly adopted system for providing continuous support in the municipality: Modelled at its core on Finnish practice for maternity and child health clinics (Neuvola)].

Objectives　This study targeted public health nurses in a Japanese municipality that had newly adopted the core components of the Finnish system to provide continuous support to families with children until preschool. It sought to analyze changes in their perceptions for activities in maternal and child health care before and after the adoption.Methods　Relevant data were collected through semi-structured focus group interviews, following an interview guide, conducted from September to October 2020. The study protocol was approved by the Ethics Committee of Osaka City University in Japan.Results　A total of 12 public health nurses participated. Prior to the adoption of the system modelled on Finnish practice, these nurses were dedicated to addressing the risks regarding families with children (especially those at high risk) through continuous engagement. However, they were hesitant to proactively engage with families at lower risk as non-continuous, one-off engagements resulted in a patchwork response. After the system was adopted, the nurses became aware of the trust cultivated with families under their care, which included those at lower risk, that enabled them to respond to the changing needs flexibly. The nurses recognized that they had acquired the capability to notice the subtle signs of changes, engage more proactively with the families under their care, and deliver the necessary preventive interventions at an early stage. They also demonstrated joy and satisfaction derived from the growth of children and mothers under their care, as well as keen awareness of the need to improve their professional skills, even though they were busy.Conclusion　These findings indicate that the continuous support system modelled on the core components from Finland enables public health nurses to proactively engage with families at lower risk and deliver preventive interventions at an early stage. The system also motivated Japanese public health nurses who found greater pleasure in their work.

C-H γ,γ,γ-Trifluoroalkylation of Quinolines via Visible-Light-Induced Sequential Radical Additions.

The photocatalyst-free C-H γ,γ,γ-trifluoroalkylation of quinolines under visible light irradiation is reported. By the combination of readily available alkenes and Umemoto's reagent II, a variety of γ,γ,γ-trifluoroalkyl groups were installed into quinolines via chemoselective sequential radical processes. This transformation provides rapid access to a variety of quinoline derivatives with scarcely explored fluoroalkyl groups, affording a novel library of N-heteroaromatic compounds and versatile building blocks for applications in medicinal chemistry.

Synthesis of Fluorine-Containing 6-Arylpurine Derivatives via Cp*Co(III)-Catalyzed C-H Bond Activation.

Cp*Co(III)-catalyzed (Cp*=pentamethylcyclopentadienyl) C-H bond functionalization of 6-arylpurines using gem-difluoroalkenes and allyl fluorides is described. The reaction with gem-difluoroalkenes afforded monofluoroalkenes with high (Z)-selectivity, while the reaction with allyl fluorides led to C-H allylation in moderate (Z)-selectivity. Both reactions proceeded using a user-friendly single-component catalyst [Cp*Co(CH3CN)3](SbF6)2 in fluorinated alcohol solvents without any additives. Robustness was also demonstrated by a preparative-scale reaction under air.

Cp*Co(III)-Catalyzed Dehydrative C-H Allylation of 6-Arylpurines and Aromatic Amides Using Allyl Alcohols in Fluorinated Alcohols.

Cp*Co(III)-catalyzed C-H allylation of various aromatic C-H bonds using allyl alcohols as allylating reagents is described. Improved reaction conditions using fluorinated alcohol solvents afforded efficient directed C-H allylation of 6-arylpurines, benzamides, and a synthetically useful Weinreb amide with good functional group compatibility.