Combined use of multiparametric high-content-screening and in vitro circadian reporter assays in neurotoxicity evaluation.

Accumulating evidence indicates that chronic circadian rhythm disruption is associated with the development of neurodegenerative diseases induced by exposure to neurotoxic chemicals. Herein, we examined the relationship between cellular circadian rhythm disruption and cytotoxicity in neural cells. Moreover, we evaluated the potential application of an in vitro cellular circadian rhythm assay in determining circadian rhythm disruption as a sensitive and early marker of neurotoxicant-induced adverse effects.

Intranasal administration enhances size-dependent pulmonary phagocytic uptake of poly(lactic-co-glycolic acid) nanoparticles.

Background: Nanoparticles exhibit distinct behaviours within the body, depending on their physicochemical properties and administration routes. However, in vivo behaviour of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, especially when administered nasally, remains unexplored; furthermore, there is a lack of comparative analysis of uptake efficiency among different administration routes. Therefore, here, we aimed to comprehensively investigate the real-time in vivo behaviour of PLGA nanoparticles across various administration routes.

A survey of the impact of COVID-19 on the management of animal experiments and laboratory animal facilities in Korea.

The pandemic has affected the lives of people all over the world. The effects of the pandemic on laboratory animal facilities and their operations through this unusual global event are poorly understood. Here, we have applied a methodological framework of qualitative approach including semi-structured interviews to investigate laboratory animal operations in Korea and how it has shaped the on-going management and laboratory operations of such facilities.

Histopathological pulmonary lesions in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques experimentally infected with wild-type severe acute respiratory syndrome coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral pneumonia characterized by acute interstitial pneumonia and diffuse alveolar damage in humans. Non-human primates (NHPs) are widely used as preclinical animal models for vaccine development against SARS-CoV-2. However, the pathological changes in NHPs have been described only in selected facets and inconsistent nomenclature is used, making it difficult to interpret and compare the outcomes between studies.

Spatial transcriptome atlas reveals pulmonary microstructure-specific COVID-19 gene signatures in cynomolgus macaques.

Characterizing the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the molecular level is necessary to understand viral pathogenesis and identify clinically relevant biomarkers. However, in humans, the pulmonary host response during disease onset remains poorly understood. Herein, we utilized a spatial transcriptome atlas to identify pulmonary microstructure-specific COVID-19 gene signatures during the acute phase of lung infection in cynomolgus macaques.

Flubendazole exposure disrupts neural development and function of zebrafish embryos (Danio rerio).

Flubendazole (FBZ) is a benzimidazole anthelmintic drug widely used for treating parasitic infections by disrupting microtubule formation and function through tubulin binding. Recently, its use has extended to include anticancer applications, leading to increased environmental exposure to benzimidazole drugs. However, the impact of FBZ on neural development in aquatic organisms, particularly in aquatic vertebrates, remains poorly understood.

Comparative spatial transcriptomic profiling of severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants infections in the lungs of cynomolgus macaques.

Recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants are generally less pathogenic than previous strains. However, elucidating the molecular basis for pulmonary immune response alterations is challenging owing to the virus's heterogeneous distribution within complex tissue structure. Here, we revealed the spatial transcriptomic profiles of pulmonary microstructures at the SARS-CoV-2 infection site in the nine cynomolgus macaques upon inoculation with the Delta and Omicron variants.

Use of laboratory animals and issues regarding the procurement of animals for research in Korea.

Background: Laboratory animals remain critical to biomedical research, despite the increasing availability of alternative approaches. Indeed, scientists strive to reduce and refine and replace the use of laboratory animals, even in the face of public calls for ever-more stringent regulation for the protection and care of animals in research. This report outlines the current status and legal regulatory issues with regard to the procurement and use of animals for research in Korea.

Postnatal exposure to trimethyltin chloride induces retinal developmental neurotoxicity in mice via glutamate and its transporter related changes.

Exposure to toxic substances during postnatal period is one of the major factors causing retinal developmental defects. The developmental toxicity of trimethyltin chloride (TMT), a byproduct of an organotin compound widely used in agriculture and industrial fields, has been reported; however, the effect on the mammalian retina during postnatal development and the mechanism have not been elucidated to date. We exposed 0.

Cynomolgus Macaque Model for COVID-19 Delta Variant.

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection.

Evaluation of exhaust air dust polymerase chain reaction as a supplement method for soiled bedding sentinel monitoring in specific pathogen free mouse facility using two different individually ventilated cage racks.

Health monitoring is essential for ensuring animal health and reliable research results. Each animal facility should establish adequate health monitoring methods, and microbiological quality control should be implemented through regular health surveillance. Recently, specific pathogen free (SPF) mice have been housed in individually ventilated cage (IVC) racks in the majority of mouse facilities globally, and health monitoring is implemented using a soiled bedding sentinel (SBS).

Improvement plans on the operation of the Institutional Animal Care and Use Committee: focusing on the case of Seoul National University.

Background: The Institutional Animal Care and Use Committee (IACUC) became compulsory in 2008 by the Animal Protection Act in Korea. Seoul National University (SNU), which conducts 5% of Korea's total animal protocol reviews and uses 10% of national laboratory animal usage, has been influential in the review of animal protocols and management of animal facilities. This study was undertaken to suggest the operational improvement of the IACUC.

Operational issues of the Institutional Animal Care and Use Committee in Korea.

Korean Institutional Animal Care and Use Committee (IACUC) is currently facing some operational pressing issues. 1) Review of the animal protocol containing controversial technology. 2) Review of the multi-institution animal protocol.

Digital selective transformation and patterning of highly conductive hydrogel bioelectronics by laser-induced phase separation.

The patterning of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels with excellent electrical property and spatial resolution is a challenge for bioelectronic applications. However, most PEDOT:PSS hydrogels are fabricated by conventional manufacturing processes such as photolithography, inkjet printing, and screen printing with complex fabrication steps or low spatial resolution. Moreover, the additives used for fabricating PEDOT:PSS hydrogels are mostly cytotoxic, thus requiring days of detoxification.

Germinal Center-Induced Immunity Is Correlated With Protection Against SARS-CoV-2 Reinfection But Not Lung Damage.

Germinal centers (GCs) elicit protective humoral immunity through a combination of antibody-secreting cells and memory B cells, following pathogen invasion or vaccination. However, the possibility of a GC response inducing protective immunity against reinfection following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. We found GC activity was consistent with seroconversion observed in recovered macaques and humans.

Next-Generation Intestinal Toxicity Model of Human Embryonic Stem Cell-Derived Enterocyte-Like Cells.

The gastrointestinal tract is the most common exposure route of xenobiotics, and intestinal toxicity can result in systemic toxicity in most cases. It is important to develop intestinal toxicity assays mimicking the human system; thus, stem cells are rapidly being developed as new paradigms of toxicity assessment. In this study, we established human embryonic stem cell (hESC)-derived enterocyte-like cells (ELCs) and compared them to existing and models.

Eliminating murine norovirus, Helicobacter hepaticus, and intestinal protozoa by embryo transfer for an entire mouse barrier facility.

Pathogens can affect physiological and immunological reactions in immunocompromised animals and genetically engineered mice. Specifically, murine norovirus (MNV), Helicobacter, and intestinal protozoa are prevalent in rodent laboratory facilities worldwide. In this study, microbiological test results of the soiled bedding of sentinel mice showed the prevalence of MNV (50.

The status and issues of the Institutional Animal Care and Use Committee of Seoul National University: from its establishment to the present day.

The Institutional Animal Care and Use Committee (IACUC) of Seoul National University (SNU) plays a key role in monitoring and managing the humane use of animals in scientific research. Here, as one of the pioneers of the IACUC in Korea, we reported SNU-IACUC operations and activities including committee establishment and legal formulation, protocol review, and post-approval monitoring of protocols, which the IACUC has undertaken in the last decade. In addition, legal regulations and improvements were also discussed, and encompassed the limited number of committee members and the single IACUC policy in Korea.

Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates.

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy.

Toxicity Assessment of Transfluthrin, Benzyl Butyl Phthalate, and 17β-Estradiol on the Primary Fibroblast of the Striped Field Mouse, Apodemus agrarius.

Environmental pollution (EP) is a well-known threat to wild animals, but its toxicological impact is poorly understood. In vitro toxicity evaluation using cells of lower predators could be a promising way to assess and monitor the effects of EPs on whole wildlife populations that are related in the food web. Here, we describe EPs' toxic effect and mechanism in the primary fibroblast derived from the embryo of the striped field mouse, Apodemus agrarius.

Albendazole exerts antiproliferative effects on prostate cancer cells by inducing reactive oxygen species generation.

Benzimidazole derivatives are used for their antihelmintic properties, but have also been reported to exert anticancer effects. In the present study, the anticancer effects of albendazole on prostate cancer cells were assessed using proliferation, clonogenic and migration assays. To investigate the anticancer mechanisms of albendazole, reactive oxygen species (ROS) levels were measured, and the expression of genes associated with oxidative stress and Wnt/β-catenin signaling was confirmed by reverse transcription-quantitative PCR and western blotting.

TALEN-mediated generation of Nkx3.1 knockout rat model.

Background: Recent developments in gene editing, using transcriptional activator-like effector nucleases (TALENs), have greatly helped the generation of genetically engineered animal models. The NK3 homeobox 1 (NKX3.1) protein plays important roles in prostate development and protein production, and functions as a tumor suppressor.

Vitrification for cryopreservation of 2D and 3D stem cells culture using high concentration of cryoprotective agents.

Background: Vitrification is the most promising technology for successful cryopreservation of living organisms without ice crystal formation. However, high concentrations (up to ~ 6-8 M) of cryoprotective agents (CPAs) used in stem cell induce osmotic and metabolic injuries. Moreover, the application of conventional slow-freezing methods to cultures of 3-D organoids of stem cells in various studies, is limited by their size.