This study prepared glass ionomer cement (GIC) containing nanoporous silica (NPS) (GIC-NPS) at 5 wt% concentrations using 3 types of NPS with different pore and particle sizes and evaluated the ...differences in their cationic ion capture/release abilities and mechanical properties. The cationic water-soluble dye was used as cationic ion. The test GIC-NPS complexes captured dyes by immersion in 1 wt% dye solutions. All the GIC-NPS complexes released dyes for 28 d, and the amount of dye released from the complexes increased with decreasing pore size; however, the particle size of NPS did not affect the amount of dye released. Additionally, GIC-NPS was able to recharge the dye, and the amount of released the dye by the complexes after recharge was almost identical to the amount released on the first charge. Although not significantly different, the compressive strength of GIC-NPS was slightly greater than that of GIC without NPS regardless of the type of NPS. These results suggest that the degree of capture and release of cationic molecules, such as drugs, can be controlled by optimizing the pore size of NPS without sacrificing its mechanical strength when its content is 5 wt%.
Abstract: Objectives: Neurotoxicity of 1-bromopropane (1-BP) has been reported in occupational exposure, but whether the chemical exerts developmental neurotoxicity is unknown. We studied the effects ...of prenatal 1-BP exposure on neuronal excitability in rat offspring. Methods: We exposed dams to 1-BP (700 ppm, 6 h a day for 20 days) and examined hippocampal slices obtained from the male offspring at 2, 5, 8, and 13 weeks of age. We measured the stimulation/response (S/R) relationship and paired-pulse ratios (PPRs) of the population spike (PS) at the interpulse intervals (IPIs) of 5 and 10 ms in the CA1 subfield. Results: Prenatal 1-BP exposure enhanced S/R relationships of PS at 2 weeks of age; however, the enhancement diminished at 5 weeks of age until it reached control levels. Prenatal 1-BP exposure decreased PPRs of PS at 2 weeks of age. After sexual maturation, however, the PPRs of PS increased at 5-ms IPI in rats aged 8 and 13 weeks. Conclusions: Our findings indicate that prenatal 1-BP exposure in dams can cause delayed adverse effects on excitability of pyramidal cells in the hippocampal CA1 subfield of offspring.
Surface nanostructures in titanium (Ti) oral implants are critical for rapid osseointegration.
The purpose of this study was to evaluate the growth of osteoblast-like (Saos-2) and epithelial-like ...(Ca9-22) cells on nanopatterned Ti films.
Ti films with 500 nm grooves and pillars were fabricated by nanoimprinting, and seeded with Saos-2 and Ca9-22 cells. Cell viability and morphology were assessed by cell proliferation assay and scanning electron microscopy, respectively.
As assessed after 1 hour, proliferation of Saos-2 cells was most robust on grooved films than on pillared and smooth films, in this order. These cells approximately doubled on grooved and pillared substrates in 24 hours and after 5 days, but not on smooth surfaces. In contrast, Ca9-22 cells favored smooth surfaces, followed by grooved and pillared films. Indeed, cells sparsely adhered to pillared films over 5 days of incubation (p < 0.05).
The data show that Saos-2 and Ca9-22 cells respond differently to different nanostructures, and highlight the potential use of nanopatterns to promote bone regeneration or to prevent epithelial downgrowth at the implant-bone interface.
The PI3K/Akt pathway plays a crucial role in the pathogenesis of multiple myeloma (MM) in the bone marrow (BM) milieu. However, efficacy of selective and potent Akt inhibition has not yet been fully ...elucidated. In this study, we, therefore, examined the biologic impact of selective and potent Akt inhibition by a novel allosteric inhibitor TAS-117. TAS-117 induced significant growth inhibition, associated with downregulation of phosphorylated Akt (p-Akt), selectively in MM cell lines with high baseline p-Akt. Cytotoxicity of TAS-117 was also observed in patient MM cells, but not in normal peripheral blood mononuclear cells. Importantly, TAS-117 induced significant cytotoxicity in MM cells even in the presence of BM stromal cells, associated with inhibition of IL6 secretion. Oral administration of TAS-117 significantly inhibited human MM cell growth in murine xenograft models. TAS-117 triggered apoptosis and autophagy, as well as induction of endoplasmic reticulum (ER) stress response with minimal expression of C/EBP homologous protein (CHOP), a fatal ER stress marker. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity, associated with increased CHOP and PARP cleavage and blockade of bortezomib-induced p-Akt, suggesting that TAS-117 augments bortezomib-induced ER stress and apoptotic signaling. Carfilzomib-induced cytotoxicity was similarly enhanced by TAS-117. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity in vivo, associated with prolonged host survival. Our results show that selective and potent Akt inhibition by TAS-117 triggers anti-MM activities in vitro and in vivo, as well as enhances cytotoxicity of proteasome inhibition, providing the preclinical framework for clinical evaluation of selective Akt inhibitors, alone and in combination with proteasome inhibitors in MM.
Background This study aimed to examine the association of suspended particulate matter (SPM) with outpatient attendance for allergic conjunctivitis. Methodology The information on air pollution, ...encompassing total hydrocarbons, non-methane hydrocarbons, methane, carbon monoxide, nitrogen oxide, nitric oxide, oxidants, and SPM alongside data concerning daily weather conditions such as temperature, wind speed, and humidity, was gathered. Subsequently, the weekly mean values for outpatient visits, air pollution, and weather parameters were computed. Results The number of outpatient visits for allergic conjunctivitis was significantly associated with SPM levels (r = 0.70, p = 0.0037), oxidant levels (r = 0.70, p = 0.0038), wind speed (r = 0.48, p = 0.0472), and humidity (r = 0.77, p = 0.0009) from January to March, as well as SPM levels (r = 0.53, p = 0.0309) and carbon monoxide (r = 0.56, p = 0.0230) from April to June. Multivariate analysis showed that SPM (odds ratio = 1.37, p = 0.0161) and wind velocity (odds ratio = 1.52, p = 0.0038) were significant predictors of the number of outpatient visits from January to December. Conclusions SPM levels were the only independent predictor of outpatient visits for allergic conjunctivitis, suggesting that SPM contributes to the pathophysiology of this condition.
Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated ...expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps.
Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot.
Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ.
These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.
Particulate matter (PM) with a median diameter <2.5 μm, is associated with respiratory and cardiovascular diseases. We previously reported the biological effects of PM in vivo, and although ...neutrophils play an important role in initiating inflammation, few reports have focused on the relationship between PM inhalation and immune responses. Here, we investigated the effect of PM particle size on neutrophils, including their endocytosis activity and reactive oxygen species (ROS) production. Flow cytometry analysis indicated that 1 μm particles are readily endocytosed by neutrophils and that endocytosis is reduced at 4 °C. Inhibitors of the pleckstrin homology domain of dynamin repressed this process; however, GTPase and clathrin inhibitors did not affect endocytosis. Endocytosis by neutrophils in Toll-like receptor 4 (TLR4)- and MyD88-knockout mice was reduced compared with that in wild-type mice, indicating that TLR4 and MyD88 are important for the process. Neutrophil-mediated endocytosis caused oxidative stress, and N-acetylcysteine enhanced endocytosis. Expression levels of the oxidative stress markers, heme oxygenase-1 and p62 protein, were increased in an endocytosis-dependent manner. Phagocytosed neutrophils produced IL-6 and TNFα, whose production was decreased by dynamin inhibitors. We observed that infiltrated CD11b-positive cells in bronchoalveolar lavage fluid endocytose PMs. Overall, these results indicate that endocytosis and ROS production via TLR4 are important for the initiation of immune responses by neutrophils.
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•One μm particles but not 3 μm are readily endocytosed by neutrophils and that endocytosis is reduced at 4 °C.•Inhibitors of the PH domain of dynamin but not of GTPase, and clathrin repressed endocytosis by neutrophils.•Endocytosis by neutrophils in Toll-like receptor 4 (TLR4)- and MyD88-knockout mice was reduced.•Endocytosis and ROS production via TLR4 are important for the initiation of immune responses by neutrophils.
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6.9 earthquake off Fukushima Prefecture, Japan, of 22 November 2016 was followed by a tsunami that struck the Japanese coast from Hokkaido in northern Japan to Wakayama Prefecture in western ...Japan. We compared the performance of a seismologically deduced single-fault model, a seismologically deduced finite fault slip model (FFM), an optimized single-fault model based on tsunami data, the FFM with horizontal shift, and the tsunami waveform inversion models of the previous studies considered for this earthquake regarding reproduction of tsunami waves by tsunami computations. It is important to discuss how these models work well because it is sometimes desirable to obtain an earthquake source model to estimate tsunami waves with a simple process obtained with limited data from the viewpoint of tsunami prediction. The seismologically deduced FFM has an advantage in terms of the information of slip regions of fault plane and was superior to the seismologically deduced single-fault model, especially in predicting amplitudes of tsunami waves. This means that when only with seismic data, the FFM could narrow the range of forecast of tsunami amplitude. In the comparison of models optimized with tsunami data, the single-fault model showed the almost equivalent performance of the tsunami waveform inversion models of previous studies regarding the waveform coincidence with observations and the horizontal location at the negative peak of the initial sea surface displacement. In case the main generation region of the tsunami is concentrated in one place, the tsunamis can be expressed by a single-fault model by conducting the detailed grid search. We also confirmed that the centroid location of centroid moment tensor (CMT) solution and the absolute location of the FFM were not necessarily suitable to express tsunamis, while the moment magnitude, the focal mechanism, the centroid depth of CMT solution, and the relative slip distribution of the FFM were effective to represent tsunamis. Since this event occurred at the shallow depth, the speed of tsunami wave is particularly slow. Therefore, it would be advisable to pay attention to the horizontal uncertainty to apply seismologically obtained solution to tsunami forecast, especially when a tsunami occurs in shallow water.
Although it is known that desert dust exacerbates allergic diseases, how it affects the onset of autoimmune diseases is unclear. No epidemiological investigations or animal experiments have been ...conducted so far to elucidate the effects of desert dust on autoimmune diseases. Here, we focused on particulate matter, such Asian sand dust (ASD) that has been known to cause adverse health effects in East Asian countries, and conducted animal experiments to examine how ASD influences type 1 diabetes (T1D), an autoimmune disease. An ASD suspension was intratracheally administered into NOD mice, which spontaneously develop T1D, for 4 times at 2-week intervals. Subsequently, the incidence of cyclophosphamide (CY)-induced diabetes was examined, which was then quantified using adoptive splenocyte-transfer assays. Kaplan-Meier curves of the cumulative T1D incidence were compared using the log-rank test, and unpaired two-tailed t tests were used for comparing the other data. We observed that ASD administration delayed T1D, and adoptive splenocytes derived from ASD-administered donor NOD mice also delayed the onset of T1D in recipient NOD mice. We further found that ASD increases concanavalin A-induced IFN-γ production and decreases regulatory T cells. Consequently, ASD suppresses the onset of T1D, activates spleen cells, and affects T-cell differentiation.
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