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Epidemiological and experimental studies have shown that di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, can aggravate allergic diseases. DEHP promotes adaptive immune responses, although its effect on the innate immune system remains largely unknown. The present study investigated the effects of DEHP on group 2 innate lymphoid cells (ILC2) that produce Th2 cytokines in response to epithelial cell-derived cytokines, such as interleukin (IL)-33. ILC2 (lineage-negative, CD45.2+, Sca1+, KLRG1+) were isolated from the lungs of C57BL/6 J mice. Co-exposure to DEHP and IL-33 significantly increased IL-5 release from ILC2, whose level was higher than that of the vehicle and IL-33 alone. The effects of DEHP in the presence of IL-33 showed an inverted-U dose-response. The present is the first report showing that DEHP exacerbates allergy through the innate immune system.

Background Although health effects of air pollutants are well documented in many countries especially in North America and Western Europe, few studies have been conducted in Thailand where pollution mix, weather conditions, and demographic characteristics are different. The present study aimed to investigate the effects of ambient air pollution on hospital admissions for cardiovascular and respiratory diseases in Bangkok, Thailand. Methods We obtained daily air pollution concentration (O3, NO2, SO2, PM10, and CO) and weather variable monitored in Bangkok from January 2006 to December 2014. Daily hospital admissions for cardiovascular and respiratory diseases were obtained from the National Health Security Office during the study period. A time-series analysis with generalized linear model was used to examine the effects of air pollution on hospital admissions by controlling for long-term trend and other potential confounders. The effect modification by age (0–14 years, 15–64 years, ≥65 years) and gender was also examined. Results An increase of 10 μg/m3 in O3, NO2, SO2, PM10, and 1 mg/m3 in CO at lag 0–1 day was associated with a 0.14% (95% CI: −0.34 to 0.63), 1.28% (0.87 to 1.69), 8.42% (6.16 to 10.74), 1.04% (0.68 to 1.41) and 6.69% (4.33 to 9.11) increase in cardiovascular admission, respectively; and 0.69% (95% CI: 0.18 to 1.21), 1.42% (0.98 to 1.85), 4.49% (2.22 to 6.80), 1.18% (0.79 to 1.57) and 7.69% (5.20 to 10.23) increase in respiratory admission, respectively. The elderly (≥65 years) seemed to be the most susceptible group to the effect of air pollution, whereas the effect estimate for male and female was not significantly different. Conclusions Results from this study contributed the evidence to support the effects of air pollution (O3, NO2, SO2, PM10, and CO) on hospital admissions for cardiovascular and respiratory diseases, which might be useful for public health intervention in Thailand.

Coronavirus disease (COVID-19) is currently a serious global issue. Epidemiological studies have identified air pollutants, including particulate matter (PM), as a risk factor for COVID-19 infection and severity of illness, in addition to numerous factors such as pre-existing conditions, aging and smoking. However, the mechanisms by which air pollution is involved in the manifestation and/or progression of COVID-19 is still unknown. In this study, we used a mouse model exposed to crude PM, collected by the cyclone method, to evaluate the pulmonary expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2), the two molecules required for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. Multiplex immunohistochemical analysis revealed that exposure to PM increased the expression of these two molecules at the same site. Furthermore, image cytometry analysis revealed increased expression of these proteins, particularly, in the alveolar type 2 cells and macrophages, which are potential targets for SARS-CoV-2. Our findings provide an experimental evidence that exposure to PM may adversely affect the manifestation and progression of COVID-19, mediated by the impact of SARS-CoV-2 on the site of entry. The study results suggest that examining these effects might help to advance our understanding of COVID-19 and aid the development of appropriate social interventions., Highlights • Studies have identified an association between particulate matter (PM) and COVID-19. • Coarse and fine particles collected by the cyclone were used for in vivo studies. • PM increases expression of both ACE2 and TMPRSS2 in the murine lung. • Alveolar type 2 cells and macrophages were identified as the main sites of expression. • PM might aggravate COVID-19 via the increased expression of these molecules.

Ambient particulate matter (PM) epidemiologically exacerbates respiratory and immune health, including allergic rhinitis (AR) and bronchial asthma (BA). Although fine and coarse particles can affect respiratory tract, the differences in their effects on the upper and lower respiratory tract and immune system, their underlying mechanism, and the components responsible for the adverse health effects have not been yet completely elucidated. In this study, ambient fine and coarse particles were collected at three different locations in Japan by cyclone technique. Both particles collected at all locations decreased the viability of nasal epithelial cells and antigen presenting cells (APCs), increased the production of IL-6, IL-8, and IL-1β from bronchial epithelial cells and APCs, and induced expression of dendritic and epithelial cell (DEC) 205 on APCs. Differences in inflammatory responses, but not in cytotoxicity, were shown between both particles, and among three locations. Some components such as Ti, Co, Zn, Pb, As, OC (organic carbon) and EC (elemental carbon) showed significant correlations to inflammatory responses or cytotoxicity. These results suggest that ambient fine and coarse particles differently affect nasal and bronchial epithelial cells and immune response, which may depend on particles size diameter, chemical composition and source related particles types.

Particulate matter with diameters

Only a few studies have investigated the association between long-term exposure to air pollution and alterations of serum lipids and blood sugar level in developing countries. The present longitudinal study examined associations between long-term air pollution exposure and serum lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] and fasting glucose (FG) in workers of the Electricity Generating Authority of Thailand (EGAT) in the Bangkok metropolitan region (BMR) of Thailand. We performed secondary analyses using the data obtained from 1,839 participants (mean age, 58.3 years as of 2002) of the EGAT1 cohort study (2002–2012). The average concentration of each air pollutants (PM10, O3, NO2, SO2, and CO) at the sub-district level in BMR from 2002 to 2012 were estimated using the ordinary kriging method. Exposure periods were averaged to 3 months prior to laboratory testing. Linear mixed effects models were used to estimate associations between air pollution and serum lipids and blood sugar. After controlling for potential confounders, an interquartile range increment of PM10, SO2, and CO was associated with elevated LDL-C [6.6% (95%CI: 4.3, 9.0), 11.1% (7.2, 15.2), and 1.9% (1.1, 2.7), respectively] and FG [2.8% (1.5, 4.2), 6.8% (4.5, 9.1), and 1.1% (0.6, 1.5), respectively]. In addition, PM10, SO2, and CO were inversely associated with HDL-C [-1.8% (−3.7, 0.1), −3.3% (−6.2, −0.3), and −1.1 (−1.7, −0.5), respectively]. O3 was negatively associated with TC, LDL-C, TG, and FG. These findings suggest inhalation of air pollutants may increase the risk of impaired metabolism of glucose and lipids.

Background Ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) are surrogate measures of atherosclerosis based on the functional performance of vessels, and are highly related to cardiovascular events. However, only a few longitudinal studies have been conducted on their associations with long-term air pollution exposure. Objective This study aimed to examine whether long-term air pollution exposure is associated with ABI and CAVI in workers of the Electricity Generating Authority of Thailand (EGAT) in the Bangkok Metropolitan Region (BMR). Methods This longitudinal study included 1261 participants (age range, 57–76 years as of 2007) of the EGAT study (2007–2017). ABI and CAVI were measured in 2007, 2012, and 2017. Annual mean concentrations of particulate matter ≤10 μm in diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO) were estimated by ordinary kriging using data from 22 background and 7 traffic monitoring stations in BMR between 2002 and 2017. Linear mixed-effects models were used to assess associations between air pollution (expressed as 1-year, 3-year, and 5-year average concentration) and ABI and CAVI (expressed as percent changes per interquartile range (IQR) increase in PM10, O3, NO2, SO2, and CO). We also applied the mixed-effect ordinal logistic models to calculate odds ratios (ORs) of having high or moderate CAVI per an IQR increase in air pollution. Results After controlling for potential confounders, 1-year average CO was negatively associated with ABI, but not significantly (−0.48%, 95% CI: −1.03, 0.07). Three-year average NO2 was positively associated with CAVI (6.67%, 95% CI: 0.21, 13.1). In contrast, 1-year average PM10 was inversely associated with CAVI although the association was not significant. Although not significantly, 1-year average NO2 and CO were positively associated with prevalence of high or moderate CAVI. Conclusions Although not statistically significant, long-term NO2 and CO exposure was associated with ABI and CAVI in the participants of the EGAT study.

Evaluation of the health effects of particulate matter with aerodynamic dias. ≤ 2.5 μm (PM2.5) should reflect realistic condition in ambient atmosphere. However, using conventional filtration methods, only extracts from PM2.5 collected on the filter can be analyzed and not the particle itself. Cyclonic separation is a technique that enables the direct analysis of the effects of the crude “powder form” of PM2.5 on respiratory health. Airway epithelial cells and antigen-presenting cells were exposed to PM2.5 collected during the same period using a conventional filtration method or cyclonic separation. PM2.5 collected using cyclonic separation led to a higher secretion of interleukins 6 and 8 (IL-6, IL-8) from airway epithelial cells, and IL-6, IL-1β, tumor necrosis factor-α (TNF-α) secretion, cluster of differentiation 86 (CD86), and dendritic and epithelial cells 205 (DEC205) expression on antigen-presenting cells, compared with the effects of filter-collected PM2.5. Furthermore, PM2.5 collected using cyclonic separation increased inflammatory cytokine levels and induced lung inflammation in vivo. These results suggest that crude PM2.5 collected using cyclonic separation causes stronger biological responses than filter-collected PM2.5. Hence, PM2.5 collected using cyclonic separation can be utilized for a reliable evaluation of the health effects of ambient PM2.5.

Background Previous studies have revealed the interactive effects of airborne pollen and particulate matter on the daily consultations for pollinosis, but it is uncertain which compositions are responsible. This study aimed to investigate the interactive effects of specific PM2.5 compositions and airborne pollen on the daily number of clinic visits for pollinosis in Fukuoka. Methods We obtained daily data on pollen concentrations, PM2.5 compositions, PM2.5 mass, gaseous pollutants (SO2, NO2, CO, and O3), and weather variables monitored in Fukuoka between February and April, 2002–2012. In total, 73,995 clinic visits for pollinosis were made at 10 clinics in Fukuoka Prefecture during the study period. A time-stratified case-crossover design was applied to examine the interactive effects. The concentrations of PM2.5 and its compositions were stratified into low ( 85th percentile) levels, and the association between airborne pollen and daily clinic visits for pollinosis was analyzed within each level. Results We found a significant interaction between specific PM2.5 compositions and airborne pollen. Specifically, the odds ratio of daily clinic visits for pollinosis per interquartile increase in pollen concentration (39.8 grains/cm2) at the average cumulative lag of 0 and 2 days during high levels of non-sea-salt Ca2+ was 1.446 (95% CI: 1.323–1.581), compared to 1.075 (95% CI: 1.067–1.083) when only moderate levels were observed. This result remained significant when other air pollutants were incorporated into the model and was fairly persistent even when different percentile cut-off points were used. A similar interaction was found when we stratified the data according to non-sea-salt SO42- levels. This finding differed from estimates made according to PM2.5 and NO3- levels, which predicted that the effects of pollen were strongest in the lower levels. Conclusions Associations between airborne pollen and daily clinic visits for pollinosis could be enhanced by high levels of specific PM2.5 compositions, especially non-sea-salt Ca2+.

We investigated the synergic effects of components of particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) on airway inflammation. Co-exposure to cadmium (Cd) and 9,10-phenanthrenequinone (9,10-PQ) additively/synergistically increased pro-inflammatory responses in airway epithelial cells, whereas co-exposure to Cd and phenanthrene resulted in no acceleration. These results suggest that the combination of metal and a quinone derivative can contribute to the exacerbation of respiratory diseases by PM2.5.

Background Epidemiological studies based on mortality and crime data have indicated that short-term exposure to higher temperature increases the risk of suicide and violent crimes. However, there are few studies on non-fatal intentional injury, especially on non-fatal self-harm which is much more common than suicide. Objectives We aimed to clarify how short-term exposure to temperature is associated with emergency ambulance transport caused by intentional injuries including acts of self-harm and assault. Method We applied a time-stratified case-crossover design using a conditional quasi-Poisson regression model for each of the 46 prefectures. All temperatures were converted to percentile value for each prefecture, to account for the varied climate across Japan. A Distributed Lag Non-Linear Model was used to explore the temperature percentile and lag pattern. The prefecture-specific results were combined using a meta-analysis with the random effects model. Result Between 2012 and 2015, the number of acts of self-harm and assault across all 46 prefectures totaled 151,801 and 95,861, respectively. We found that as the temperature increased, the relative risk (RRs) for both self-harm and assault behaviors increased in a nearly linear manner. The pooled relative risk at the 99th percentile temperature for self-harm behavior was 1.11 (95% CI: 1.07, 1.15) compared with the risk at the 1st percentile temperature, and that for assault was 1.12 (95% CI: 1.08, 1.16) at lag 0. The RRs were highest at lag0 and less than 1 at lag7–20. Conclusion The present study found that short-term exposure to higher temperature promotes the risk of emergency ambulance transport due to acts of self-harm and assault. The lag pattern indicates a possible “displacement” effect. These results suggest that exposure to high temperatures may potentially function as a trigger for intentional injuries.

Numerous epidemiological studies have demonstrated that short-term exposure to ambient PM2.5 increases mortality and morbidity. Investigating the association using hourly ambient PM2.5 exposure may provide important insights, as current evidence is limited mostly to daily lag term. This study aimed to investigate the hourly association between ambient PM2.5 concentrations and all-cause emergency ambulance dispatches (EAD) in 11 cities in Japan. We used a time-stratified case-crossover design and examined the hourly lags of ambient PM2.5 up to 24 h (unconditional distributed lags and moving average lags) using a conditional Poisson regression model. A significant increase in all-cause EAD was observed at lag 0 h [relative risk (RR): 1.0037 (95% CI: 1.0000, 1.0074)] and all moving average lags. The highest RR was observed within the first 6 h (at lag 0–5 h) [RR: 1.0091 (95% CI: 1.0068, 1.0114)], with a slight ascending pattern. This was followed by a descending pattern at lags 0–11, 0–17, and 0–23 h, but significant positive RR was observed even at lag 0–23 h, when the lowest RR was observed [RR: 1.0072 (95% CI: 1.0044, 1.0100)]. Though similar pattern was observed among the elderly, a different pattern was observed among the children (gradually ascending pattern). We conclude that all-cause EAD could be triggered by ambient PM2.5 exposure with very short lags.

Exposure to fine particulate matter (PM2.5) is a potential aggravating factor for respiratory and allergic diseases. However, which PM2.5 sources are associated with such diseases remains unclear. This study aimed to investigate the association of PM2.5 sources with allergic and respiratory symptoms in schoolchildren. PM2.5 samples were collected in Fukuoka during the spring in 2014 and 2015. Asian dust was observed in 2014. Ion components, elemental components, and organic components were analyzed. Positive matrix factorization (PMF) was conducted to calculate PM2.5 concentrations from each source. Mixed logistic regression analysis with a random intercept for each schoolchild was performed to evaluate the association of components and sources with symptoms. Among 2317 schoolchildren, the mean prevalence was 28.9%, 23.6%, 11.2%, and 11.4% for lower respiratory, nasal, ocular, and skin symptoms, respectively. PMF identified the following six PM2.5 sources “Secondary sulfate and coal combustion”, “Secondary nitrate”, “Heavy oil combustion”, “Sea salt”, “Soil” and “Traffic emission”. An interquartile range of PM2.5 mass was associated with nasal (Odds ratios 1.08, 95% confidence interval [1.03, 1.13]), ocular (1.10, [1.04, 1.16]), and skin symptoms (1.13, [1.06, 1.20]). Among the source factors, “Heavy oil combustion” was significantly associated with nasal symptom (1.11, [1.05, 1.18]) while “Sea salt” was associated with nasal (1.06, [1.02, 1.11]) and skin (1.073, [1.01, 1.14]) symptoms. We found “Soil”, which might be affected by Asian dust, was associated with ocular (1.07, [1.03, 1.10]) and skin (1.05, [1.01, 1.08]) symptoms. Further studies in other seasons or places are needed to clarify the influence of PM2.5 sources on children's health.

We measured the levels of some biological metals: copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) in the cerebrospinal fluid (CSF) in patients with neurodegenerative diseases (52 patients with amyotrophic lateral sclerosis (ALS)), 21 patients with Alzheimer's disease (AD), and 20 patients with Parkinson's disease (PD) by inductively coupled plasma mass spectrometry (ICP-MS). The diagnoses were additionally supported by neuroimaging techniques for AD and PD. In ALS, the levels of Mg (p

Metallothioneins (MTs) are metal binding proteins and have four isoforms. MT-3, known as growth inhibitory factor (GIF), exists mainly in the central nervous system. It regulates zinc levels and exhibits a neuroprotective effect in the various types of brain diseases. However, the reports demonstrate that the relation between MT-3 and psychiatric disorder is still unknown. In the present study, the authors carried out behavioral tests on MT-3 knock-out (KO) mice. The duration of the MT-3 KO mice's social interactions were significantly shorter than that of the wild-type (WT) mice. The acoustic startle response of the MT-3 KO mice showed diminished prepulse inhibition (PPI) at all prepulse intensities. However, the locomotor activity tests of the MT-3 KO mice displayed normal circadian rhythm, activity, and habituation to a novel environment. In the novel object recognition test, the MT-3 KO mice exhibited normal memory. These findings indicate that abnormalities of psychological behavior were observed in the MT-3 KO mice. Further experiments will be needed to clarify the involvement of MT-3 in higher brain function.

Background DISC1 has been suggested as a causative gene for psychoses in a large Scottish family. We recently identified FEZ1 as an interacting partner for DISC1. To investigate the role of FEZ1 in schizophrenia and bipolar disorder, case–control association analyses were conducted in Japanese cohorts. Methods We performed a mutation screen of the FEZ1 gene and detected 15 polymorphisms. Additional data on informative polymorphisms were obtained from public databases. Eight single nucleotide polymorphisms (SNPs) were analyzed in 119 bipolar disorder and 360 schizophrenic patients and age- and gender-matched control subjects. All genotypes were determined with the TaqMan assay, and selected samples were confirmed by sequencing. Results The two adjacent polymorphisms displayed a nominally significant association with schizophrenia (IVS2+1587G>A, p = .014; 396T p = .024). Homozygotes with the Glu123 allele were observed in only a small portion (2%) of schizophrenia patients but not in control subjects or bipolar patients. Conversely, no SNPs displayed allelic, genotypic, or haplotypic associations with bipolar disorder. Conclusions A modest association between FEZ1 and schizophrenia suggests that this gene and the DISC1-mediated molecular pathway might play roles in the development of schizophrenia, with FEZ1 affecting only a small subset of Japanese schizophrenia patients.

A method for the analysis of the sialo-N-glycans in glycoproteins was established by the electrokinetic chromatography mode of capillary electrophoresis (CE) in sodium dodecyl sulfate (SDS) micelles as 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives, using sialo-N-glycans in fetuin as a model. Six major and some minor peaks were observed for the N-glycans in fetuin, which were well separated from each other using 50 mM phosphate buffer, pH 6.0, containing SDS to a concentration of 30 mM in an uncoated fused-silica capillary, and these peaks were assigned to sialo-N-glycans having either of the biantennary or beta1-3/beta1-4 linked galactose-containing complex type triantennary N-glycans as the basic structures, by an indirect method based on the assignment of the peaks in high-performance liquid chromatography separated in parallel with CE and peak collation between these two separation methods. The attaching position of the sialic acid residue was determined using the linkage preference of neuraminidase isozymes. The established system is considered to be useful for routine analysis of microheterogeneity of the carbohydrate moiety of this model glycoprotein from the following reasons: (1) the derivatization with PMP proceeds quantitatively under mild conditions without causing release of the sialic acid residue, (2) the derivatives can be sensitively detected by UV absorption, (3) the procedure is simple, rapid and reproducible. Preliminary results of N-glycan analysis for several other glycoproteins under these conditions are also presented.

Background & Aims: Prostaglandins (PGs) have important roles in the regulation of gastric acid secretion. The aim of this study was to examine the possible presence of PG receptors on the gastric enterochromaffin-like (ECL) carcinoid of Mastomys natalensis , which might be a useful model of normal ECL cells. Methods: A [ 3 H]PGE 2 binding experiment was performed by using the ECL tumor membrane, and intracellular signal transduction was studied in the cells. In addition, Northern blot analysis using EP 2 and EP 3 receptor complementary DNAs was conducted. Results: [ 3 H]PGE 2 specifically bound to the tumor cell membrane, and the binding was displaced by various PGs with a potency order of PGE 1 = PGE 2 > enprostil >PGF 2α . Although PGE 1 and PGE 2 stimulated 5′-cyclic adenosine monophosphate (cAMP) production, neither PGF 2α nor enprostil had any effect. On the other hand, all of PGE 1 , PGE 2 , PGF 2α , and enprostil attenuated the forskolin-induced cAMP production. Moreover, enprostil inhibited histamine release induced by forskolin. However, on pertussis toxin treatment, PGE 2 paradoxically enhanced the forskolin-induced increase of cAMP production. Finally, the presence of EP 2 and EP 3 receptor messenger RNAs was confirmed by RNA blot analysis. Conclusions: The ECL carcinoid tumor cells of Mastomys seem to possess two subtypes of PGE receptor: EP 2 linked to cAMP production and EP 3 coupled with inhibitory guanosine 5′-triphosphate-binding proteins mediating the inhibition of cAMP production.

The primary structure of nucleoside diphosphate (NDP) kinase from spinach leaves has been deduced from its cDNA sequence. A λgt11 cDNA library derived from spinach leaves was screened using an antibody against NDP kinase I, which we previously purified to electrophoretic homogeneity ( T. Nomura, T. Fukui, and A. Ichikawa, 1991 , Biochim. Biophys. Acta 1077, 47–55). The cDNA sequences of positive clones contained the amino acid coding region (444 base pairs) for NDP kinase I as well as 5′ and 3′ noncoding regions of 33 and 361 base pairs, respectively. The cDNAs hybridized to a 1.1-kb mRNA. NDP kinase I contains 148 amino acid residues with a molecular mass of 16,305, which is in excellent agreement with that of the purified enzyme (16 kDa). Homology was found between the sequence of spinach NDP kinase I and those of the rat, Myxococcus xanthus , and Dictyostelium discoideum NDP kinases, as well as the human Nm 23-gene product and the awd protein of Drosophila melanogaster .

A cDNA clone for the mouse thromboxane A2 receptor was isolated from mouse lung cDNA library. The cDNA has a 1,023 base pair open reading frame which encodes a protein of 341 amino acid residues. STA2 and U-46619 induced inward current in Xenopus laevis oocytes injected with the transcript of the clone. Specific binding of [3H]S-145 was found in membranes of COS-1 cells transfected with the cDNA (Kd = 3.3 nM) and was displaced with unlabeled prostaglandins and thromboxane analogues in the order of S-145 greater than STA2 greater than U-46619 greater than PGD2 greater than PGF2 alpha = PGE2. Northern blot analysis demonstrated that thromboxane A2 receptor mRNA is expressed abundantly in thymus, spleen and lung.