Effect of Ethanol Vapor Inhalation Treatment on Lethal Respiratory Viral Infection With Influenza A

Ethanol (EtOH) effectively inactivates enveloped viruses in vitro, including influenza and severe acute respiratory syndrome coronavirus 2. Inhaled EtOH vapor may inhibit viral infection in mammalian respiratory tracts, but this has not yet been demonstrated. Here we report that unexpectedly low EtOH concentrations in solution, approximately 20% (vol/vol), rapidly inactivate influenza A virus (IAV) at mammalian body temperature and are not toxic to lung epithelial cells on apical exposure. Furthermore, brief exposure to 20% (vol/vol) EtOH decreases progeny virus production in IAV-infected cells. Using an EtOH vapor exposure system that is expected to expose murine respiratory tracts to 20% (vol/vol) EtOH solution by gas-liquid equilibrium, we demonstrate that brief EtOH vapor inhalation twice a day protects mice from lethal IAV respiratory infection by reducing viruses in the lungs without harmful side effects. Our data suggest that EtOH vapor inhalation may provide a versatile therapy against various respiratory viral infectious diseases.journal articl

Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, the mechanisms underlying this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identified several factors that are associated with COVID-19 vaccine-induced adaptive immune responses. BNT162b2-induced T cell response is positively associated with late monocyte responses and inversely associated with baseline mRNA expression of activation protein 1 (AP-1) transcription factors. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with mRNA expression of AP-1, as well as a gene encoding an enzyme producing prostaglandin E2 (PGE2), which promotes AP-1 expression, and inversely correlated with BNT162b2-induced T-cell responses. These results suggest that baseline AP-1 expression, which is affected by commensal microbial activity, is a negative correlate of BNT162b2-induced T-cell responses.journal articl

Interfacial interactions of bioadhesive materials with human hard tissues

Recently, in dental practice, tooth reconstruction can be performed using dental adhesive technology following either a “glass-ionomer”, an “etch-and-rinse” or a “self-etch” approach. Glass-ionomer cements are well-known to possess an auto-adhesive capability without requiring any surface pre-treatment. The fundamental bonding mechanism of resin-based materials to enamel and dentin is essentially based on an exchange process, in which minerals removed from the dental hard tissues are replaced by resin monomers. These resin monomers, upon polymerization become micro-mechanically interlocked in the created porosities. Besides micro-mechanical interlocking through hybridization, an additional chemical interaction between functional monomers/polymers and tooth substrate components has been found to be important. In this review, we focus on how the chemical interaction of the biomaterial-hard tissue interface can improve bond durability, especially using chemical analytical techniques

Innate immunity in an in vitro murine blastocyst model using embryonic and trophoblast stem cells

The immune system has two broad components—innate and adaptive immunity. Adaptive immunity becomes established only after the onset of hematopoiesis, whereas the innate immune system may be actively protecting organisms from microbial invasion much earlier in development. Here, we address the question of whether the innate immune system functions in the early-stage embryo, i.e., the blastocyst. The innate immune system was studied by using in vitro blastocyst models, e.g., embryonic stem (ES) and trophoblast stem (TS) cell cultures. The expression of Toll-like receptors (TLR)-2, -3, and -5 could be detected in both ES and TS cells. The expression of interferon (IFN)-β was induced by the addition of polyinosinic:polycytidylic acid [poly(I:C)] in TS cells, but not ES cells, although TLR-3 was expressed at the same level in both cell types. In turn, ES cells responded to IFN-β exposure by expressing IFN-induced anti-viral genes, e.g., RNA-dependent protein kinase and 2′, 5′-oligoadenylate synthetase (OAS). Neither a reduction in ES cell proliferation nor cell death in these cultures was observed after IFN-β stimulation. Furthermore, OAS1a expression was induced in ES/TS co-cultures after poly(I:C) stimulation, but was not induced when either cell type was cultured alone. In conclusion, TS cells react to poly(I:C) stimulation by producing IFN-β, which induces IFN-inducible genes in ES cells. This observation suggests that the trophectoderm, the outer layer of the blastocyst, may respond to viral infection, and then induce anti-viral gene expression via IFN-β signaling to the blastocyst inner cell mass

Different micro/nano-scale patterns of surface materials influence osteoclastogenesis and actin structure

The surface topography of a material can influence osteoclast activity. However, the surface structural factors that promote osteoclast activity have not yet been investigated in detail. Therefore, we investigated osteoclastogenesis by testing various defined patterns with different dimensions and shapes. The systematic patterns, made of a cyclo-olefin polymer, were prepared at a micron-, submicron-, and nano-scale with a groove, hole, or pillar shape with a 1:1 pitch ratio. RAVV264.7 cells were cultured on these patterns in the presence of the receptor activator of NF-kappa B ligand (RANKL). Osteoclast formation was induced in the order: pillar > groove >= hole. The two-dimensional factors also indicated that submicron-sized patterns strongly induced osteoclast formation. The optimal pillar dimension for osteoclast formation was 500 nm in diameter and 2 mu m in height Furthermore, we observed two types of characteristic actin structure, i.e., belt-like structures with small hollow circles and isolated ring-like structures, which formed on or around the pillars depending on size and height. Furthermore, resorption pits were observed mainly on the top of calcium phosphate-coated pillars. Thus, osteoclasts prefer convex shapes, such as pillars for differentiation and resorption. Our results indicate that osteoclastogenesis can be controlled by designing surfaces with specific morphologies

Social networks, leisure activities and maximum tongue pressure: cross-sectional associations in the Nagasaki Islands Study

OUTCOME MEASURES: Tongue pressure was measured three times, and the maximum tongue pressure was used for analysis. A multivariable adjusted regression model was used to calculate parameter estimates (B) for tongue pressure.RESULTS: Having a social network involving neighbours (B=2.43, P=0.0001) and taking part in leisure activities (B=1.58, P=0.005) were independently associated with higher tongue pressure, but there was no link with social networks beyond neighbours (B=0.23, P=0.77). Sex-specific analyses showed that for men, having a partner was associated with higher tongue pressure, independent of the number of people in the household (B=2.26, P=0.01), but there was no association among women (B=-0.24, P=0.72; P-interaction=0.059).CONCLUSIONS: Having a social network involving neighbours and taking part in leisure activities were independently associated with higher tongue pressure. Marital status may be an important factor in higher tongue pressure in men.OBJECTIVES: Social environment is often associated with health outcomes, but epidemiological evidence for its effect on oral frailty, a potential risk factor for aspiration, is sparse. This study aimed to assess the association between social environment and tongue pressure, as an important measure of oral function. The study focused on family structure, social networks both with and beyond neighbours, and participation in leisure activities.DESIGN: A population-based cross-sectional study.SETTING: Annual health check-ups in a rural community in Japan.PARTICIPANTS: A total of 1982 participants, all over 40 years old. Anyone with missing data for the main outcome (n=14) was excluded

Phosphoenolpyruvate regulates the Th17 transcriptional program and inhibits autoimmunity

Aerobic glycolysis, a metabolic pathway essential for effector T cell survival and proliferation, regulates differentiation of autoimmune T helper (Th) 17 cells, but the mechanism underlying this regulation is largely unknown. Here, we identify a glycolytic intermediate metabolite, phosphoenolpyruvate (PEP), as a negative regulator of Th17 differentiation. PEP supplementation or inhibition of downstream glycolytic enzymes in differentiating Th17 cells increases intracellular PEP levels and inhibits interleukin (IL)-17A expression. PEP supplementation inhibits expression of signature molecules for Th17 and Th2 cells but does not signif-icantly affect glycolysis, cell proliferation, or survival of T helper cells. Mechanistically, PEP binds to JunB and inhibits DNA binding of the JunB/basic leucine zipper transcription factor ATF-like (BATF)/interferon regula-tory factor 4 (IRF4) complex, thereby modulating the Th17 transcriptional program. Furthermore, daily admin-istration of PEP to mice inhibits generation of Th17 cells and ameliorates Th17-dependent autoimmune encephalomyelitis. These data demonstrate that PEP links aerobic glycolysis to the Th17 transcriptional program, suggesting the therapeutic potential of PEP for autoimmune diseases.journal articl