記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

With the rapid development of alternative methods based on the spirit of animal welfare, the publications of animal studies evaluating endpoints such as cancer have been extremely reduced. We performed a 26-week inhalation exposure studies of titanium dioxide nanoparticles (TiO₂ NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) mice model for detecting carcinogenicity. Male and female rasH2 mice were exposed to 2, 8 or 32 mg/m³ of TiO₂ NPs for 6 h/day, 5 days/week for 26 weeks. All tissues and blood were collected and subjected to biological and histopathological analyses. TiO₂ NPs exposure induced deposition of particles in lungs in a dose-dependent manner in each exposure group. Exposure to TiO₂ NPs, as well as other organs, did not increase the incidence of lung tumors in any group, and pulmonary fibrosis and pre-neoplastic lesions were not observed in all groups. Finally, the cell proliferative activity of alveolar epithelial type 2 cells was examined, and it was not increased by exposure to TiO₂ NPs. This is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO₂ NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m³, which is considered to be a high concentration.

DOI： 10.1038/s41598-022-19139-y

その他リンク： https://www.nature.com/articles/s41598-022-19139-y

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Background

A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study.

Results

Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent.

Conclusions

Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation.

DOI： 10.1186/s12989-022-00478-7

その他リンク： https://link.springer.com/article/10.1186/s12989-022-00478-7/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Background

In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace.

Methods

Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m³ CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days.

Results

CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m³ and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m³. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m³ CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m³ was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages.

Conclusions

Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m³ CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.

Graphical Abstract

DOI： 10.1186/s12989-022-00468-9

その他リンク： https://link.springer.com/article/10.1186/s12989-022-00468-9/fulltext.html

記述言語：日本語   出版者・発行元：(一社)日本職業・災害医学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

REarranged during Transition (RET) is a tyrosine kinase associated with the development of several malignancies. Identification of RET kinase inhibitors promises valuable therapeutic tools for the intervention of RET-driven tumors. Most currently available tyrosine kinase inhibitors target the ATP binding site, but there are several drawbacks of these ATP-competitive drugs. Therefore, there is a need to develop new kinase inhibitors with alternative mechanisms of action. We have previously reported that a conserved cysteine in the MXXCW motif of RET is crucial to the disulfide-bonded dimerization-linked activation of RET kinases. Reagents which bind to this cysteine may inhibit the activity of RET kinases through disulfide-bond mediated dimerization. Here, we examine the potential of MXXCW motif-containing peptides as candidate kinase inhibitors. We demonstrate that MXXCW motif-containing peptides bind to RET in a redox-sensitive manner and block enzymatic activity, causing inhibition of the RET-dependent activity of extracellular signal-regulated kinases and effectively reducing the malignant potential of RET-papillary thyroid carcinoma-1 (PTC)-expressing cells. These motif-containing peptides were also found to be effective against the drug resistant mutant of RET. The inhibition of RET kinase activity by these peptides resulted in suppression of RET-PTC-1-mediated cancer growth. The great potency of these cysteine targeted peptides could indicate promising approaches for novel molecular-targeted therapies for RET-associated cancers.

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/w11091803

記述言語：日本語   出版者・発行元：(一社)日本毒性学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Melanin is a dark naturally occurring pigment produced in nature and in many organisms. Although several reports have demonstrated applications for melanins in various therapeutic treatments, to date, no research has examined the anti-allergic effect of melanin. In this study, we for the first time found that solubilized or synthesized soluble melanin acts as a potent inhibitor of the degranulation of mast cells. We found that squid-ink-derived melanin significantly inhibited antigen-IgE-FcεRI-mediated degranulation of the mucosal mast cell line RBL-2H3. A homogenized melanin nanoparticle prepared by laser ablation also clearly suppressed antigen-induced mast cell degranulation. We also successfully solubilized synthetic melanin in a neutral biochemical buffer and found that it also significantly inhibited IgE-sensitized mast cells. The anti-degranulation activity of synthesized melanin was abolished in the melanin fraction below 50-kD molecular weight. All melanins used in this study did not exert significant cell death. Signal transduction analysis revealed that melanin suppressed antigen-triggered phosphorylation of signaling molecules as well as calcium influx. Transmission electron microscopy revealed that homogenized melanin nanoparticles partially attached to the cell surface and some nanoparticles were internalized to the cell. Flow cytometry revealed that the number of FcεRI-bound IgE molecules was decreased by melanin. Fluorescence recovery after photobleaching analysis indicated that melanin attenuated both plasma membrane and cytoplasmic fluidity, implying that melanin increased their viscosities. In vivo experiments using passive systemic anaphylaxis (PSA) and passive cutaneous anaphylaxis (PCA) mouse models demonstrated that oral administration of melanin accelerated the recovery of decreased body temperature after antigen infection in PSA, and combination sensitization of IgE with melanin attenuated antigen-induced extravasation in PCA. These findings indicated that melanin exhibits preventative effects against IgE-mast cell-mediated anaphylaxis. This study provides the first evidence that homogenized melanin may be a potential therapeutic agent for diseases involving mast cells.

DOI： 10.1016/j.bcp.2019.02.015

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pesticide Science Society of Japan  

DOI： 10.1584/jpestics.d17-061

担当区分：責任著者   記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Di-2-ethylhexyl phthalate (DEHP) is one of the most widely used phthalates. Metabolites of DEHP are detectable in majority of the population. Findings on adverse health outcomes, particularly birth weight in association with prenatal exposure to DEHP remain equivocal. Besides, there is insufficient evidence to address influence on metabolic function from epidemiological studies.
Thus, our objective was to investigate cord blood adipokine levels and birth size in association with prenatal DEHP exposure in prospective birth cohort study. Mono-2-methylhexyl phthalate (MEHP), primary metabolite of DEHP was determined as exposure by using maternal blood sample of 3rd trimester. Leptin and adiponectin levels in cord blood were measured as markers of metabolic function. Birth weight and length were obtained from birth record. Association between maternal MEHP levels and cord blood adiponectin and leptin levels, birth weight and ponderal index (PI) were examined for 167 mother-child pairs who had both MEHP and cord blood adipokine measurements.
The median MEHP level was 8.81 ng/ml and the detection rate was 100%. There was no sex difference in MEHP levels. Both leptin and adiponectin levels were higher in girls than in boys. MEHP level was positively associated with adiponectin level among boys and was negatively associated with leptin level among girls. MEHP level were negatively associated with PI only in girls and this could be due to decreased leptin level.
This study suggested that prenatal DEHP exposure may be associated with cord blood adipokine and birth size. The influence potentially be sex-specific and could be more significant in girls. (C) 2016 Published by Elsevier B.V.

DOI： 10.1016/j.scitotenv.2016.11.051

Web of Science

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MICROBIOL RES FOUNDATION  

Anodes are crucial in determining the electricity recovery of microbial fuel cells (MFCs). In this study, graphene oxide (GO) was used as an anodic material for electricity recovery from artificial dialysis wastewater (ADWW). Anaerobic incubation of ADWW with GO for 21 days produced a hydrogel complex containing embedded microbial cells and microbially reduced GO (rGO). The rGO complex recovered 540 to 810 mu A/cm(3) of catalytic current from ADWW after 10 days of electrochemical cultivation at 200 mV (vs. Ag/AgCl), which was approximately thirty times higher than that recovered from graphite felt (GF), a representative anode in MFCs. High-throughput sequencing analysis of prokaryotic 16S rRNA genes revealed a predominance of the Geobacter genus (35% of all prokaryotic sequences identified), particularly in the rGO complex after 20 days of polarization. The superior electricity recovery of the rGO complex was attributable to enhanced direct electron transfer via a well-developed biofilm, while indirect electron transfer via an electron mediator occurred in culture using GF.

DOI： 10.2323/jgam.2016.10.001

Web of Science

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18 months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study.
Maternal blood samples collected between 23 and 41 weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18 month of age. For the final analysis, 328 participants were included.
The median levels of maternal MEHP was 10.6 ng/ml, neonatal TSH and FT4 was 2.20 mu U/ml and 2.03 ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18 month.
In this study, prenatal DEHP exposure did not showadverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary. (C) 2016 Published by Elsevier B.V.

DOI： 10.1016/j.scitotenv.2016.05.098

Web of Science

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Graphene oxide (GO) is reduced by certain exoelectrogenic bacteria, but its effects on bacterial growth and metabolism are a controversial issue. This study aimed to determine whether GO functions as the terminal electron acceptor to allow specific growth of and electricity production by exoelectrogenic bacteria. Cultivation of environmental samples with GO and acetate as the sole substrate could specifically enrich exoelectrogenic bacteria with Geobacter species predominating (51-68% of the total populations). Interestingly, bacteria in these cultures self-aggregated into a conductive hydrogel complex together with biologically reduced GO (rGO). A novel GO-respiring bacterium designated Geobacter sp. strain R4 was isolated from this hydrogel complex. This organism exhibited stable electricity production at >1000 mu A/cm(3) (at 200 mV vs Ag/AgCl) for more than 60 d via rGO while temporary electricity production using graphite felt. The better electricity production depends upon the characteristics of rGO such as a large surface area for biofilm growth, greater capacitance, and smaller internal resistance. This is the first report to demonstrate GO-dependent growth of exoelectrogenic bacteria while forming a conductive hydrogel complex with rGO. The simple put-and-wait process leading to the formation of hydrogel complexes of rGO and exoelectrogens will enable wider applications of GO to bioelectrochemical systems.

DOI： 10.1038/srep21867

Web of Science

記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：AMER INST PHYSICS  

Artificial dialysis wastewater (ADWW) generally contains 800-2,200 mg L-1 of organic matter. Prior to its discharge to the sewage system, ADWW must be treated in order to reduce organic matter to less than 600 mg L-1. This study assesses the applicability of a microbial fuel cell (MFC) to the reduction of organic matter in ADWW as an alternative pre-treatment system to aeration. In the MFC, conductive floccular aggregates microbially produced from graphene oxide (GO-flocs) were applied as an anode material in the MFC. The GO-flocs were obtained by anaerobic incubation of graphene oxide (GO) with microorganisms in ADWW at 28 degrees C for a minimum of 10 days. During incubation, GO in the mixture was transformed into black conductive floccular aggregates having 0.12 mS cm(-1), suggesting the microbial reduction of GO to the reduced form. The produced GO-flocs were then used as the anode material in a cylindrical MFC, which was filled with ADWW and covered with a floating, platinum (Pt)-coated carbon cathode. The MFC was polarized via an external resistance of 10 Omega and applied for 120 days by replacing half of the supernatant of the MFC with fresh ADWW, every 6-9 days. As a result, the MFC achieved a 128 mg L-1 d(-1) chemical oxygen demand (CODCr) removal rate. For example, the MFC contained 1,500 mg-CODCr L-1 just after replacement, with this concentration being reduced to 1,000 mg-CODCr L-1 after 6-9 days of incubation. At the same time, the MFC showed an average power density of 28 mW m(-2) and a maximum power density of 291 mW m(-2). These results suggest that a MFC packed with GO-flocs can be used as an alternative biotreatment system, replacing the energy-intensive aeration process.

DOI： 10.1063/1.4941206

Web of Science

記述言語：英語  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media S.A.  

The effects of graphene oxide (GO) on electricity generation in soil microbial fuel cells (SMFCs) and plant microbial fuel cell (PMFCs) were investigated. GO at concentrations ranging from 0 to 1.9 g·kg-1 was added to soil and reduced for 10 days under anaerobic incubation. All SMFCs (GO-SMFCs) utilizing the soils incubated with GO produced electricity at a greater rate and in higher quantities than the SMFCs which did not contain GO. In fed-batch operations, the overall average electricity generation in GO-SMFCs containing 1.0 g·kg-1 of GO was 40 ± 19 mW·m-2, which was significantly higher than the value of 6.6 ± 8.9 mW·m-2 generated from GO-free SMFCs (p &lt
0.05). The increase in catalytic current at the oxidative potential was observed by cyclic voltammetry (CV) for GO-SMFC, with the CV curve suggesting the enhancement of electron transfer from oxidation of organic substances in the soil by the reduced form of GO. The GO-containing PMFC also displayed a greater generation of electricity compared to the PMFC with no added GO, with GO-PMFC producing 49 mW·m-2 of electricity after 27 days of operation. Collectively, this study demonstrates that GO added to soil can be microbially reduced in soil, and facilitates electron transfer to the anode in both SMFCs and PMFCs.

DOI： 10.3389/fbioe.2015.00042

Scopus

記述言語：日本語   出版者・発行元：日本環境動物昆虫学会  

CiNii Books

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PESTICIDE SCI SOC JAPAN  

The fate and transport of pretilachlor, one of the most widely used rice-paddy herbicides in Japan, were monitored in a rice paddy plot for 28 days after its application in the five study years. The effect of the percolation rate on herbicide loss was investigated. The concentration of pretilachlor in the paddy water was at its highest level within 2 days of application. The maximum concentration in percolated water was lower, and it was reached 1 or 2 days later than that in the paddy water. Almost all the pretilachlor loss was caused by percolation. The pretilachlor loss, as estimated from the amount that was applied and the cumulative percolation loss, ranged from 7.4 to 16.3%. In the five study years, the average percolation rate for the 7 days following application ranged from 11.5 to 29.3 mm/day. The pretilachlor loss increased proportionally with the percolation rate for 7 days following application. (c) Pesticide Science Society of Japan

DOI： 10.1584/jpestics.D11-032

Web of Science

記述言語：日本語  

開催年月日： 2022年

記述言語：日本語  

開催年月日： 2019年5月

記述言語：日本語   会議種別：口頭（一般）  

記述言語：日本語  

開催年月日： 2018年7月

記述言語：日本語   会議種別：ポスター発表  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語