Adverse effects of diethyl phthalate and butyl benzyl phthalate on circadian rhythms and sleep patterns in zebrafish larvae.

The zebrafish, a diurnal vertebrate, is commonly used in circadian rhythm studies due to its genetic and neurological similarities to humans. Circadian rhythms, which regulate sleep, neurotransmitter, behavior, and physiological responses to environmental changes, can be disrupted by various environmental factors. Phthalic acid esters (PAEs) are pervasive endocrine disruptors that individuals are frequently exposed to in daily life.

ToxSTAR: drug-induced liver injury prediction tool for the web environment.

Summary: Drug-induced liver injury (DILI) is a challenging endpoint in predictive toxicology because of the complex reactive metabolites that cause liver damage and the wide range of mechanisms involved in the development of the disease. ToxSTAR provides structural similarity-based DILI analysis and in-house DILI prediction models that predict four DILI subtypes (cholestasis, cirrhosis, hepatitis and steatosis) based on drug and drug metabolite molecules.

Availability And Implementation: ToxSTAR is freely available at https://toxstar.

In vitro neurotoxicity evaluation of biocidal disinfectants in a human neuron-astrocyte co-culture model.

Biocidal disinfectants (BDs) that kill microorganisms or pathogens are widely used in hospitals and other healthcare fields. Recently, the use of BDs has rapidly increased as personal hygiene has become more apparent owing to the pandemic, namely the coronavirus outbreak. Despite frequent exposure to BDs, toxicity data of their potential neurotoxicity (NT) are lacking.

Developmental and Neurotoxicity of Acrylamide to Zebrafish.

Acrylamide is a commonly used industrial chemical that is known to be neurotoxic to mammals. However, its developmental toxicity is rarely assessed in mammalian models because of the cost and complexity involved. We used zebrafish to assess the neurotoxicity, developmental and behavioral toxicity of acrylamide.

Novel Calcium Aminoclay (CaAC)-Vitamin C Hybrid: Cytotoxicity Assessment in HaCaT Cells and Embryotoxicity Assay in Zebrafish.

Vitamin C (VC) is well-known as a hydrophilic antioxidant commonly used in cosmeceutical formulations due to its protection and maintenance of youthful skin. Aminoclay (AC), a synthetic organic-nanoclay, has shown great potential for delivery of VC. However, the practical cosmeceutical applications of aminoclay for delivery of VC are severely limited due to the paucity of reported research on its cytotoxicity to human skin.

Live-cell screening platform using human-induced pluripotent stem cells expressing fluorescence-tagged cytochrome P450 1A1.

Human-induced pluripotent stem cells (hiPSCs) are invaluable sources for drug screening and toxicity tests because of their differentiation potential and proliferative capacity. Recently, the CRISPR-Cas9-mediated homologous recombination system has enabled reporter knock-ins at desired loci in hiPSCs, and here, we generated a hiPSC reporter line expressing mCherry-tagged cytochrome P450 1A1 (CYP1A1), which can be utilized to screen for the modulators of aryl hydrocarbon receptor (AHR) in live cells. CYP1A1-mCherry hiPSCs exhibited typical characteristics of pluripotent stem cells such as marker expression, differentiation potential, and normal karyotype.

Correlation of α/γ-FeO nanoparticles with the toxicity of particulate matter originating from subway tunnels in Seoul stations, Korea.

According to the increasing concern about particulate matter (PM) pollution at subway systems, particularly its potentially severe effects on human health, this study investigated the constituents, characteristics, and toxicity of PM collected at underground subway stations in Seoul, Korea. It was found that α/γ-FeO NPs, which are considered as thermal products derived from the brake-wheel-rail interface, were the main components of PM (57.6% and 48% of PM and PM, respectively).

Plausibility of the zebrafish embryos/larvae as an alternative animal model for autism: A comparison study of transcriptome changes.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by impaired or abnormal social interaction and communication and by restricted and repetitive behaviour. ASD is highly prevalent in Asia, Europe, and the United States, and the frequency of ASD is growing each year. Recent epidemiological studies have indicated that ASD may be caused or triggered by exposure to chemicals in the environment, such as those in the air or water.

Two zinc-aminoclays' in-vitro cytotoxicity assessment in HeLa cells and in-vivo embryotoxicity assay in zebrafish.

Two zinc-aminoclays [ZnACs] with functionalized primary amines [(-CH)NH] were prepared by a simple sol-gel reaction using cationic metal precursors of ZnCl and Zn(NO) with 3-aminopropyl triethoxysilane [APTES] under ambient conditions. Due to the facile interaction of heavy metals with primary amine sites and Zn-related intrinsic antimicrobial activity, toxicity assays of ZnACs nanoparticles (NPs) prior to their environmental and human-health applications are essential. However, such reports remain rare.

Xeno-sensing activity of the aryl hydrocarbon receptor in human pluripotent stem cell-derived hepatocyte-like cells.

Although hepatocyte-like cells derived from human pluripotent stem cells (hPSC-HLCs) are considered a promising model for predicting hepatotoxicity, their application has been restricted because of the low activity of drug metabolizing enzymes (DMEs). Here we found that the low expression of xenobiotic receptors (constitutive androstane receptor, CAR; and pregnane X receptor, PXR) contributes to the low activity of DMEs in hPSC-HLCs. Most CAR- and PXR-regulated DMEs and transporters were transcriptionally down-regulated in hPSC-HLC.

Quinoline compound KM11073 enhances BMP-2-dependent osteogenic differentiation of C2C12 cells via activation of p38 signaling and exhibits in vivo bone forming activity.

Recombinant human bone morphogenetic protein (rhBMP)-2 has been approved by the FDA for clinical application, but its use is limited due to high cost and a supra-physiological dose for therapeutic efficacy. Therefore, recent studies have focused on the generation of new therapeutic small molecules to induce bone formation or potentiate the osteogenic activity of BMP-2. Here, we show that [4-(7-chloroquinolin-4-yl) piperazino][1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]methanone (KM11073) strongly enhances the BMP-2-stimulated induction of alkaline phosphatase (ALP), an early phase biomarker of osteoblast differentiation, in bi-potential mesenchymal progenitor C2C12 cells.

KR-62980 suppresses lipid metabolism through inhibition of cytosolic NADP isocitrate dehydrogenase in zebrafish.

Peroxisome proliferator-activated receptor γ (PPARγ) is a target of antidiabetic drugs. However, many PPARγ activators, including rosiglitazone, show unwanted side effects, such as weight gain. The KR-62980 [1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carboxylic acid ethyl ester], a novel partial agonist of PPARγ, is a new compound for diabetes with antihyperglycemic activity and weak antiadipogenic activity.

Synthesis of LipidGreen2 and its application in lipid and fatty liver imaging.

We have developed LipidGreen2, a second generation small molecule probe for lipid imaging. LipidGreen2 has a better fluorescence signal compared with the previous LipidGreen, and selectively stains neutral lipids in cells and fat deposits in live zebrafish. We also demonstrate the application of LipidGreen2 for detecting fatty liver.

Predicted drug-induced bradycardia related cardio toxicity using a zebrafish in vivo model is highly correlated with results from in vitro tests.

Several in vivo and in vitro studies have assessed methods of evaluating the cardio toxicity of compounds during drug development due to its importance for predicting human toxicity. However, in vivo/in vitro relationships have not yet been reported using a zebrafish model. This study determined the bradycardia of 15 compounds by evaluating the change in heart beat rate (HBR) in zebrafish, hERG fluorescence polarization (hERG-FP), and ionic current change using a patch clamp (hERG-PC).

Normal forebrain development may require continual Wnt antagonism until mid-somitogenesis in zebrafish.

During normal forebrain development in vertebrates, rostral neural tissue must be protected from Wnt signals via the actions of locally expressed Wnt antagonistic factors. In zebrafish zygotic oep (Zoep) mutants, forebrain structure is severely disrupted with reduced expression of the Wnt antagonists secreted frizzled related protein1 and dickkopf1. To analyze the temporal effects of Wnt antagonism on forebrain development, we generated transgenic zebrafish that overexpressed the dominant negative form of frizzled8a (DNfz8a) in wild-type and Zoep mutants under the control of a heat-inducible promoter.

Her4 is necessary for establishing peripheral projections of the trigeminal ganglia in zebrafish.

Transcripts of notch and its target genes have been detected in some differentiating neurons. However, the role of Notch in neuronal differentiation remains poorly defined. Here, we show that a subset of differentiating sensory neurons in the trigeminal ganglia express her4.

Eye field requires the function of Sfrp1 as a Wnt antagonist.

Wnts have been shown to provide a posteriorizing signal that has to be repressed in the specification of vertebrate forebrain region. Previous studies have shown that Wnt activation by LiCl treatment causes an expansion of optic stalk and mid-hindbrain boundary, whereas eye and ventral diencephalon in the forebrain region were reduced. However, the molecular mechanism, by which inhibits Wnt activity in the forebrain remains poorly defined.

Cellular defense against UVB-induced phototoxicity by cytosolic NADP(+)-dependent isocitrate dehydrogenase.

Ultraviolet (UV) radiation is known as a major cause of skin photoaging and photocarcinogenesis. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species. Recently, we have shown that NADP(+)-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage.