Pulmonary toxicity of tungsten trioxide nanoparticles in an inhalation study and an intratracheal instillation study.

Objectives: We conducted inhalation and intratracheal instillation studies in order to examine the effects of tungsten trioxide (WO ) nanoparticles on the lung, and evaluated whether or not the nanoparticles would cause persistent lung inflammation.

Methods: In the inhalation study, male 10-week-old Fischer 334 rats were classified into 3 groups. The control, low-dose, and high-dose groups inhaled clean air, 2, and 10 mg/m WO nanoparticles, respectively, for 6 h each day for 4 weeks.

Roles of Gonadotropin Receptors in Sexual Development of Medaka.

The gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are secreted from the pituitary and bind to the FSH receptor (FSHR) and LH receptor (LHR) to regulate gonadal development in vertebrates. Previously, using -knockout (KO) medaka (), we demonstrated that FSH regulates ovarian development by elevating estrogen levels. However, the -KO phenotype in medaka is poorly characterized.

Examination of Surfactant Protein D as a Biomarker for Evaluating Pulmonary Toxicity of Nanomaterials in Rat.

This work studies the relationship between lung inflammation caused by nanomaterials and surfactant protein D (SP-D) kinetics and investigates whether SP-D can be a biomarker of the pulmonary toxicity of nanomaterials. Nanomaterials of nickel oxide and cerium dioxide were classified as having high toxicity, nanomaterials of two types of titanium dioxides and zinc oxide were classified as having low toxicity, and rat biological samples obtained from 3 days to 6 months after intratracheal instillation of those nanomaterials and micron-particles of crystalline silica were used. There were different tendencies of increase between the high- and low-toxicity materials in the concentration of SP-D in bronchoalveolar-lavage fluid (BALF) and serum and in the expression of the SP-D gene in the lung tissue.

Long-term observation of pulmonary toxicity of toner with external additives following a single intratracheal instillation in rats.

Objectives: Along with technological innovations for improving the efficiency of printing, nanoparticles have been added to the surface of toners, and there is concern about the harmful effects of those components. We investigated, through a long-term observation following intratracheal instillation using rats, whether exposure to a toner with external additives can cause tumorigenesis.

Methods: Female Wistar rats were intratracheally instilled with dispersed toner at low (1 mg/rat) and high (2 mg/rat) doses, and the rats were sacrificed at 24 months after exposure, after which we examined pulmonary inflammation, histopathological changes, and DNA damage in the lung.

Development of a Novel Enhanced Biosensor System for Real-Time Monitoring of Fish Stress Using a Self-Assembled Monolayer.

Wireless biosensor systems were developed in our lab for monitoring blood glucose concentrations in fish as an indicator of fish stress. However, uniform immobilization of the enzyme on the surface of the electrode is difficult, so the sensor response is typically reduced at a range of high glucose concentrations during the stress monitoring. In this study, we attempted to enhance sensor response by using a self-assembled monolayer-immobilized enzyme.

Synthesis of a Peptide-Human Telomere DNA Conjugate as a Fluorometric Imaging Reagent for Biological Sodium Ion.

A peptide-oligonucleotide conjugate (1) was synthesized by the attachment of FAM, TAMRA, and biotin moieties to a telomere DNA sequence of 5'-TAG GGT TAG GGT TAG GGT TAG GG-3'. This conjugate was induced to be an anti-parallel structure in the presence of sodium ion (Na), whereas a hybrid one was formed under potassium ion (K) as a monitoring by circular dichromic spectra. The conformation change of this conjugate gave an effective FRET signal change upon the addition of NaCl, compared with the case of KCl.

Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials.

Background: In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed intratracheal instillation exposures (dose: 0.2-1.

Novel method for mass producing genetically sterile fish from surrogate broodstock via spermatogonial transplantation†.

A stable system for producing sterile domesticated fish is required to prevent genetic contamination to native populations caused by aquaculture escapees. The objective of this study was to develop a system to mass produce stock for aquaculture that is genetically sterile by surrogate broodstock via spermatogonial transplantation (SGTP). We previously discovered that female medaka carrying mutations on the follicle-stimulating hormone receptor (fshr) gene become sterile.

Lovastatin induced Kruppel like factor 2 (), Kruppel like factor 6 () and Ras homolog family member B () genes and preferentially led to viability reduction of Cisplatin-resistant cells.

It was reported that statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used to prevent hypercholesterolemia, have antitumor activity in several cancers. In this study, we investigated the cell viability of statins in Cisplatin-resistant HCP4 and PCDP5 cells compared with their parent Hela and PC3 cells, respectively, and found that HCP4 and PCDP5 cells were 37-fold and 18-fold more resistant to Cisplatin but 13-fold and 7-fold more sensitive to Lovastatin by cell proliferation assay. Lovastatin induced the apoptosis of HCP4 cells more rapidly and to greater extent than in Hela cells as assessed by flow cytometry and western blotting analyses.

Biopersistence of NiO and TiO₂ Nanoparticles Following Intratracheal Instillation and Inhalation.

The hazards of various types of nanoparticles with high functionality have not been fully assessed. We investigated the usefulness of biopersistence as a hazard indicator of nanoparticles by performing inhalation and intratracheal instillation studies and comparing the biopersistence of two nanoparticles with different toxicities: NiO and TiO₂ nanoparticles with high and low toxicity among nanoparticles, respectively. In the 4-week inhalation studies, the average exposure concentrations were 0.

Basic study of intratracheal instillation study of nanomaterials for the estimation of the hazards of nanomaterials.

In order to examine the usefulness of intratracheal instillation of nanoparticles for the screening of the harmful effects of nanoparticles, we performed intratracheal instillation studies of nanomaterials on rats using different delivery devices and postures as a basic study. Multiwall carbon nanotubes (MWCNTs) with a geometric mean length and secondary diameter of 2.16 μm and 752 nm, respectively, were used as the nanomaterials.

Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts.

rag1 zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels.

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project.

Assessment of Pulmonary Toxicity Induced by Inhaled Toner with External Additives.

We investigated the harmful effects of exposure to a toner with external additives by a long-term inhalation study using rats, examining pulmonary inflammation, oxidative stress, and histopathological changes in the lung. Wistar rats were exposed to a well-dispersed toner (mean of MMAD: 2.1 m) at three mass concentrations of 1, 4, and 16 mg/m for 22.

evaluation of a combination treatment involving anticancer agents and an aurora kinase B inhibitor.

Aurora kinase B (AURKB) inhibitors are regarded as potential molecular-targeting drugs for cancer therapy. The present study evaluated the cytotoxic effect of a combination of AZD1152-hQPA, an AURKB inhibitor, and various anticancer agents on the HeLa human cervical cancer cell line, as well as its cisplatin-resistant equivalent HCP4 cell line. It was demonstrated that AZD1152-hQPA had an antagonistic effect on the cytotoxicity of cisplatin, etoposide and doxorubicin, but had a synergistic effect on that of all-trans-retinoic acid (ATRA), Am80 and TAC-101, when tested on HeLa cells.

New approach for monitoring fish stress: A novel enzyme-functionalized label-free immunosensor system for detecting cortisol levels in fish.

Fishes display a wide variation in their physiological responses to stress, which is clearly evident in the plasma corticosteroid changes, chiefly cortisol levels in fish. As a well-known indicator of fish stress, a simple and rapid method for detecting cortisol changes especially sudden increases is desired. In this study, we describe an enzyme-functionalized label-free immunosensor system for detecting fish cortisol levels.

Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.

We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water.

Analysis of the sexual development-promoting region of Schizophyllum commune TRP1 gene.

This study aims to elucidate the mechanism of sexual development of basidiomycetous mushrooms from mating to fruit body formation. Sequencing analysis showed the TRP1 gene of basidiomycete Schizophyllum commune encoded an enzyme with three catalytic regions of GAT (glutamine amidotransferase), IGPS (indole-3-glycerol phosphate synthase), and PRAI (5-phosphoribosyl anthranilate isomerase); among these three regions, the trp1 mutant (Trp(-)) had a missense mutation (L→F) of a 338th amino acid residue of the TRP1 protein within the IGPS region. To investigate the function of IGPS region related to sexual development, dikaryons with high, usual, and no expression of the IGPS region of TRP1 gene were made.

Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity.

Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs.

Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung.

NiO nanoparticles were administered to rat lungs via intratracheal instillation or inhalation. During pulmonary toxicity caused by NiO nanoparticles, the induction of oxidative stress is a major factor. Both intratracheal instillation and inhalation of NiO nanoparticles induced pulmonary oxidative stress.

Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation.

We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO nanoparticles.

TALENs-mediated gene disruption of myostatin produces a larger phenotype of medaka with an apparently compromised immune system.

Although myostatin, a suppressor of skeletal muscle development and growth, has been well studied in mammals, its function in fish remains unclear. In this study, we used a popular genome editing tool with high efficiency and target specificity (TALENs; transcription activator-like effector nucleases) to mutate the genome sequence of myostatin (MSTN) in medaka (Oryzias latipes). After the TALEN pair targeting OlMyostatin was injected into fertilized medaka eggs, mutant G0 fish carrying different TALENs-induced frameshifts in the OlMSTN coding sequence were mated together in order to transmit the mutant sequences to the F1 generation.

Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles.

In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.

Comparison between whole-body inhalation and nose-only inhalation on the deposition and health effects of nanoparticles.

Objectives: We performed the two inhalation exposures, whole-body inhalation and nose-only inhalation, to investigate the pulmonary deposition and health effects of the two inhalation methods.

Methods: In both methods, we exposed rats to the same TiO2 nanoparticles at almost the same exposure concentration for 6 h and compared the deposited amounts of nanoparticles and histopathological changes in the lungs. Rats were exposed to rutile-type TiO2 nanoparticles generated by the spray-dry method for 6 h.

Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation.

In order to investigate the pulmonary toxicity of titanium dioxide (TiO) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.