Does drug-induced liver injury still occur after sevoflurane anesthesia? -A case report.

BACKGROUND: Several factors contribute to post-anesthetic hepatic dysfunction, including a decrease in oxygen supply to the liver, direct physical compression of the liver, viral hepatitis, blood transfusions, preexisting hepatic dysfunction, and the use of hepatotoxic drugs. Diagnosing volatile anesthetic drug-induced liver injury (VA-DILI) involves excluding these causes. CASE: The patient underwent total mastectomy under anesthesia using sevoflurane. He had diabetes, and no abnormal results were found on preoperative laboratory examinations, and surgery was uneventful. Abnormal laboratory findings were observed after surgery, including an aspartate aminotransferase level of 1,417 IU/L, an alanine aminotransferase level of 2,176 IU/L, and a total bilirubin level of 3.8 mg/dl. He presented with symptoms of mild icteric sclera, fatigue, and pruritus. After ruling out other causes of liver injury, we concluded that these results indicated VA-DILI. CONCLUSIONS: VA-DILI, though rare, we should be aware of the association between the disease and the use of halogenated anesthetics.

In vitro analysis of antiviral immune response against avian influenza virus in chicken tracheal epithelial cells.

Objective: Avian influenza virus (AIV) infections first affect the respiratory tract of chickens. The epithelial cells activate the host immune system, which leads to the induction of immune-related genes and the production of antiviral molecules against external environmental pathogens. In this study, we used chicken tracheal epithelial cells (TECs) in vitro model to investigate the immune response of the chicken respiratory tract against avian respiratory virus infections. Methods: Eighteen-day-old embryonic chicken eggs were used to culture the primary chicken TECs. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC) analysis of epithelial cell-specific gene makers were performed to confirm the characteristics, morphology, and growth pattern of primary cultured chicken TECs. Moreover, to investigate the cellular immune response to AIV infection or polyinosinic-polycytidylic acid (poly (I:C)) treatment, the TECs were infected with the H5N1 virus or poly (I:C). Then, immune responses were validated by RT-qPCR and western blotting. Results: The TECs exhibited polygonal morphology and formed colony-type cell clusters. The RT-qPCR results showed that H5N1 infection induced a significant expression of antiviral genes in TECs. We found that TECs treated with poly (I:C) and exposed to AIV infection-mediated activation of signaling pathways, leading to the production of antiviral molecules (e.g., pro-inflammatory cytokines and chemokines), were damaged due to the loss of junction proteins. We observed the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, which are involved in inflammatory response by modulating the release of pro-inflammatory cytokines and chemokines in TECs treated with poly (I:C) and pathway inhibitors. Furthermore, our findings indicated that poly (I:C) treatment compromises the epithelial cell barrier by affecting junction proteins in the cell membrane. Conclusion: Our study highlights the utility of in vitro TEC models for unraveling the mechanisms of viral infection and understanding host immune responses in the chicken respiratory tract.

Pharmacologic inhibition of Il6st/gp130 improves dermatological inflammation and pruritus.

Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals. We hypothesized accordingly that pharmacological inhibition of Il6st can alter dermatitis pathology. Treatment with SC-144 and bazedoxifene, two representative small molecule Il6st inhibitors with different binding modes led to moderate but significant improvement of skin conditions in a 1-chloro-2,4-dinitrobenzene animal model. Part of cytokine expressions indicating the dermatological index were normalized particularly when treated with SC-144. Pruritic behaviors were blunted, also possibly giving limited contribution to disease improvement. In psoriatic skin and itch of an imiquimod animal model, those two treatments appeared to be relatively moderate. Collectively, pharmacological inhibition of Il6st seems to lessen pathological irritation. Inversely, this experimental attempt newly implies that Il6st participates in pathological mechanisms. In conclusion, we suggest Il6st as a novel target for improving dermatitis, and that agents with suitable efficacy and safety for its modulation are translatable.

Prevention of UVB-Induced Photoaging by an Ethyl Acetate Fraction from Allomyrina dichotoma Larvae and Its Potential Mechanisms in Human Dermal Fibroblasts.

Allomyrina dichotoma larvae (ADL) is an insect type that is used ethnopharmacologically to treat various diseases; however, its use as an antiaging treatment has not been widely studied. Previously, we found that an ethyl acetate (EA) fraction derived from an ADL extract (ADLE) has a high polyphenol content and antioxidant properties. In this study, we identified the underlying molecular mechanism for the protective effect of the EA fraction against UVB-induced photodamage in vitro and ex vivo. UVB treatment increased intracellular reactive oxygen species levels and DNA damage; the latter of which was significantly decreased following cotreatment with the EA fraction. Biological markers of aging, such as p16INK4a, p21WAF1, and senescence-associated ß-gal levels, were induced by UVB treatment but significantly suppressed following EA-fraction treatment. UVB-induced upregulation of matrix metalloproteinase (MMP)-1 and downregulation of COL1A1 were also reversed by EA-fraction treatment in both cells and a 3D skin model, which resulted in increased keratin and collagen deposition. Moreover, EA-fraction treatment inhibited the phosphorylation of MAPKs (p38, ERK, and JNK) and nuclear factor (NF-)-kB and decreased the levels of inflammatory cytokines in UVB-treated cells. The results indicate that an EA fraction from ADLE ameliorates UVB-induced degradation of COL1A1 by inhibiting MMP expression and inactivating the MAPK/NF-κB p65/AP-1 signaling pathway involved in this process.

Fasudil and viscosity of gelatin promote hepatic differentiation by regulating organelles in human umbilical cord matrix-mesenchymal stem cells.

BACKGROUND: Human mesenchymal stem cells originating from umbilical cord matrix are a promising therapeutic resource, and their differentiated cells are spotlighted as a tissue regeneration treatment. However, there are limitations to the medical use of differentiated cells from human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs), such as efficient differentiation methods. METHODS: To effectively differentiate hUCM-MSCs into hepatocyte-like cells (HLCs), we used the ROCK inhibitor, fasudil, which is known to induce endoderm formation, and gelatin, which provides extracellular matrix to the differentiated cells. To estimate a differentiation efficiency of early stage according to combination of gelatin and fasudil, transcription analysis was conducted. Moreover, to demonstrate that organelle states affect differentiation, we performed transcription, tomographic, and mitochondrial function analysis at each stage of hepatic differentiation. Finally, we evaluated hepatocyte function based on the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4 in mature HLCs. RESULTS: Fasudil induced endoderm-related genes (GATA4, SOX17, and FOXA2) in hUCM-MSCs, and it also induced lipid droplets (LDs) inside the differentiated cells. However, the excessive induction of LDs caused by fasudil inhibited mitochondrial function and prevented differentiation into hepatoblasts. To prevent the excessive LDs formation, we used gelatin as a coating material. When hUCM-MSCs were induced into hepatoblasts with fasudil on high-viscosity (1%) gelatin-coated dishes, hepatoblast-related genes (AFP and HNF4A) showed significant upregulation on high-viscosity gelatin-coated dishes compared to those treated with low-viscosity (0.1%) gelatin. Moreover, other germline cell fates, such as ectoderm and mesoderm, were repressed under these conditions. In addition, LDs abundance was also reduced, whereas mitochondrial function was increased. On the other hand, unlike early stage of the differentiation, low viscosity gelatin was more effective in generating mature HLCs. In this condition, the accumulation of LDs was inhibited in the cells, and mitochondria were activated. Consequently, HLCs originated from hUCM-MSCs were genetically and functionally more matured in low-viscosity gelatin. CONCLUSIONS: This study demonstrated an effective method for differentiating hUCM-MSCs into hepatic cells using fasudil and gelatin of varying viscosities. Moreover, we suggest that efficient hepatic differentiation and the function of hepatic cells differentiated from hUCM-MSCs depend not only on genetic changes but also on the regulation of organelle states.

Ultrasound-guided subcostal approach of transversus abdominis plane block compared with wound infiltration for postoperative analgesia following laparoscopic cholecystectomy: A systematic review and meta-analysis.

BACKGROUND: Despite laparoscopic cholecystectomy (LC) is a commonly performed operation under ambulatory setting, significant postoperative pain is still a major concern. The ultrasound-guided subcostal approach of transversus abdominis plane (sTAP) blocks and wound infiltration (WI) are both widely practiced techniques to reduce postoperative pain in patients undergoing LC. Although these methods have been shown to relieve postoperative pain effectively, the relative analgesic efficacy between ultrasound-guided sTAP blocks and WI is not well known. METHODS: We searched PubMed, EMBASE, and CENTRAL to identify all randomized controlled trials (RCTs) comparing ultrasound-guided sTAP block versus WI for postoperative pain control in adult patients undergone LC. The search was performed until May 2023. Primary outcome was defined as 24-hour cumulative opioid consumption. Secondary outcomes were postoperative pain scores and the incidence of postoperative nausea and vomiting (PONV). RESULTS: Finally, 6 RCTs were included, and data from 314 participants were retrieved. Postoperative 24-hour opioid consumption was significantly lower in ultrasound-guided sTAP group than in the WI group with a mean difference of -6.67 (95% confidence interval: -9.39 to - 3.95). The ultrasound-guided sTAP group also showed significantly lower pain scores. Incidence of PONV did not significantly differ between the 2 groups. CONCLUSIONS: We conclude that there is low to moderate evidence to advocate that ultrasound-guided sTAP block has better analgesic effects than WI in patients undergoing LC. Further trials are needed with robust methodology and clearly defined outcomes.

Microplastic accumulation dynamics in Han river headwaters: Sediment interactions and environmental implication.

The prevalence of microplastic (MP) contamination has become a significant environmental concern due to its pervasive nature and persistent effects. While sediments are considered major repositories for MPs, information on their spatial distribution within these matrices is insufficient. This research examined both the horizontal and vertical presence of MPs in the sediments surrounding Lake Paldang in South Korea, alongside a comprehensive evaluation of the physicochemical characteristics of the samples obtained. The total content of MPs varied from 2.15 to 122.2 particles g-1. The average contents of MPs on surface sediments were 40.47, 34.14, 5.01, and 8.19 particles g-1 in north mainstream (NM), south mainstream (SM), tributary (TB), and Tributary catchment (TC) based on Sonae Island, Gyeongan stream, respectively. The most abundant MP types were polyethylene (PE), polytetrafluoroethylene (PTFE), and polypropylene (PP), accounting for more than 70% of the total MPs. The most abundant sizes of MPs were within 45-100 µm. At all sediment depths, polymers were distributed in the order PE, PP, and polyester in NM, SM, and TC, respectively, whereas PTFE mainly occurred in the surface layer. MPs distribution also exhibited seasonal variation as larger inflows and flow rates varied with season.

Changes in Adolescent Health Behavior and the Exacerbation of Economic Hardship During the COVID-19 Pandemic: A Cross-sectional Study From the Korea Youth Risk Behavior Survey.

OBJECTIVES: This study investigated the association between exacerbated economic hardship during the coronavirus disease 2019 (COVID-19) pandemic and changes in the health behaviors of Korean adolescents. METHODS: We analyzed data from the 2021 Korea Youth Risk Behavior Survey and included 44 908 students (22 823 boys and 22 085 girls) as study subjects. The dependent variables included changes in health behaviors (breakfast habits, physical activity, and alcohol use) that occurred during the COVID-19 pandemic. The aggravation of economic hardship by COVID-19 and the subjective economic status of the family were used as exposure variables. Multiple logistic regression analysis was utilized to calculate the prevalence odds ratios (PORs). RESULTS: Severe exacerbation of a family's economic hardship due to COVID-19 was negatively associated with the health behaviors of adolescents, including increased breakfast skipping (POR, 1.85; 95% confidence interval [CI], 1.55 to 2.21 for boys and POR, 1.56; 95% CI, 1.27 to 1.92 for girls) and decreased physical activity (POR, 1.37; 95% CI, 1.19 to 1.57 for boys and POR, 1.38; 95% CI, 1.19 to 1.60 for girls). These negative changes in health behaviors were further amplified when combined with a low subjective family economic status. CONCLUSIONS: The experience of worsening household hardship can lead to negative changes in health behavior among adolescents. It is crucial to implement measures that address the economic challenges that arise from stressful events such as COVID-19 and to strive to improve the lifestyles of adolescents under such circumstances.

Atypical presentation of DeBakey type I aortic dissection mimicking pulmonary embolism in a pregnant patient: a case report.

Aortic dissection in pregnant patients results in an inpatient mortality rate of 8.6%. Owing to the pronounced mortality rate and speed at which aortic dissections progress, efficient early detection methods are crucial. Here, we highlight the importance of early chest computed tomography (CT) for differentiating aortic dissection from pulmonary embolism in pregnant patients with dyspnea. We present the unique case of a 38-year-old pregnant woman with elevated D-dimer and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, initially suspected of having a pulmonary embolism. Initial transthoracic echocardiography did not indicate aortic dissection. Surprisingly, after an emergency cesarean section, a chest CT scan revealed a DeBakey type I aortic dissection, indicating a diagnostic error. Our findings emphasize the need for early chest CT in pregnant patients with dyspnea and elevated D-dimer and NT-proBNP levels. This case report highlights the critical importance of considering both aortic dissection and pulmonary embolism in the differential diagnosis of such cases, which will inform future clinical practice.

Analysis of miRNA expression in the trachea of Ri chicken infected with the highly pathogenic avian influenza H5N1 virus.

BACKGROUND: Highly pathogenic avian influenza virus (HPAIV) is considered a global threat to both human health and the poultry industry. MicroRNAs (miRNA) can modulate the immune system by affecting gene expression patterns in HPAIV-infected chickens. OBJECTIVES: To gain further insights into the role of miRNAs in immune responses against H5N1 infection, as well as the development of strategies for breeding disease-resistant chickens, we characterized miRNA expression patterns in tracheal tissues from H5N1-infected Ri chickens. METHODS: miRNAs expression was analyzed from two H5N1-infected Ri chicken lines using small RNA sequencing. The target genes of differentially expressed (DE) miRNAs were predicted using miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then conducted. Furthermore, using quantitative real-time polymerase chain reaction, we validated the expression levels of DE miRNAs (miR-22-3p, miR-146b-3p, miR-27b-3p, miR-128-3p, miR-2188-5p, miR-451, miR-205a, miR-203a, miR-21-3p, and miR-200a-3p) from all comparisons and their immune-related target genes. RESULTS: A total of 53 miRNAs were significantly expressed in the infection samples of the resistant compared to the susceptible line. Network analyses between the DE miRNAs and target genes revealed that DE miRNAs may regulate the expression of target genes involved in the transforming growth factor-beta, mitogen-activated protein kinase, and Toll-like receptor signaling pathways, all of which are related to influenza A virus progression. CONCLUSIONS: Collectively, our results provided novel insights into the miRNA expression patterns of tracheal tissues from H5N1-infected Ri chickens. More importantly, our findings offer insights into the relationship between miRNA and immune-related target genes and the role of miRNA in HPAIV infections in chickens.

Chicken miR-26a-5p modulates MDA5 during highly pathogenic avian influenza virus infection.

MicroRNAs play crucial roles in immune-related pathways in host animals. In this study, we aimed to investigate the systemic biological function of gga-miR-26a-5p, a chicken miRNA, in the immune responses to HPAIV H5N1 infection in the Vietnamese Ri chicken line. Our results showed a significant downregulation in gga-miR-26a expression in the lung tissue of Ri chickens during HPAIV H5N1 infection. Overexpression of gga-miR-26a and the reporter construct, either containing the wildtype or mutant melanoma differentiation-associated protein 5 (MDA5) 3' untranslated region (3' UTR)-luciferase, into a chicken fibroblast cell line, revealed that gga-miR-26a can act as a direct translational repressor of MDA5 by targeting the 3' UTRs. Additionally, miR-26a negatively regulated the expression of the signaling molecules related to the MDA5 signaling pathway, including MDA5, mitochondrial antiviral-signaling (MAVS), interferon regulatory factor 7 (IRF7), p38 mitogen-activated protein kinases, and nuclear factor-kappa B (NF-κB). Moreover, downstream of the IRF7 and NF-κB signaling pathway, the proinflammatory cytokines such as IL-1ß, IFN-γ, IFN-α, IFN-ß, and the interferon-stimulated gene (Mx1) were, likewise, downregulated by the overexpression of gga-miR-26a. These findings suggest that gga-miR-26a-5p serves as an important regulator in the MDA5 signaling pathway and antiviral response. Overall, our results contribute to an improved understanding of the biological functions of gga-miR-26a-5p, alongside the mechanisms underlying the MDA5 signaling pathway, and the antiviral response to HPAIV-H5N1 infection in chickens.

Pamoic acid-induced peripheral GPR35 activation improves pruritus and dermatitis.

BACKGROUND AND PURPOSE: Pruritic dermatitis is a disease with a considerable unmet need for treatment and appears to present with not only epidermal but also peripheral neuronal complications. Here, we propose a novel pharmacological modulation targeting both peripheral dorsal root ganglion (DRG) sensory neurons and skin keratinocytes. GPR35 is an orphan G-protein-coupled receptor expressed in DRG neurons and has been predicted to downregulate neuronal excitability when activated. Modulator information is currently increasing for GPR35, and pamoic acid (PA), a salt-forming agent for drugs, has been shown to be an activator solely specific for GPR35. Here, we investigated its effects on dermatitic pathology. EXPERIMENTAL APPROACH: We confirmed GPR35 expression in peripheral neurons and tissues. The effect of PA treatment was pharmacologically evaluated in cultured cells in vitro and in in vivo animal models for acute and chronic pruritus. KEY RESULTS: Local PA application mitigated acute non-histaminergic itch and, consistently, obstructed DRG neuronal responses. Keratinocyte fragmentation under dermatitic simulation was also dampened following PA incubation. Chronic pruritus in 1-chloro-2,4-dinitrobenzene and psoriasis models were also moderately but significantly reversed by the repeated applications of PA. Dermatitic scores in the 1-chloro-2,4-dinitrobenzene and psoriatic models were also improved by its application, indicating that it is beneficial for mitigating disease pathology. CONCLUSION AND IMPLICATIONS: Our findings suggest that pamoic acid activation of peripheral GPR35 can contribute to the improvement of pruritus and its associated diseases.

Influence of Chemical and Genetic Manipulations on Cellular Organelles Quantified by Label-Free Optical Diffraction Tomography.

Label-free optical diffraction tomography provides three-dimensional imaging of cells and organelles, along with their refractive index (RI) and volume. These physical parameters are valuable for quantitative and accurate analysis of the subcellular microenvironment and its connections to intracellular biological properties. In biological and biochemical cell analysis, various invasive cell manipulations are used, such as temperature change, chemical fixation, live cell staining with fluorescent dye, and gene overexpression of exogenous proteins. However, it is not fully understood how these various manipulations affect the physicochemical properties of different organelles. In this study, we investigated the impact of these manipulations on the cellular properties of single HeLa cells. We found that after cell fixation and an increase in temperature, the RI value of organelles, such as the nucleus and cytoplasm, significantly decreased overall. Interestingly, unlike the cell nuclei, cytoplasmic RI values were hardly detected after membrane permeation, indicating that only intracytoplasmic components were largely lost. Additionally, our findings revealed that the expression of GFP and GFP-tagged proteins significantly increased the RI values of organelles in living cells compared to the less effective RI changes observed with chemical fluorescence staining for cell organelles. The result demonstrates that distinct types of invasive manipulations can alter the microenvironment of organelles in different ways. Our study sheds new light on how chemical and genetic manipulations affect organelles.

Developmental toxicity of fipronil and its two metabolites towards zebrafish (Danio rerio) embryos.

Fipronil (FIL) use is currently regulated in several countries due to its specific toxicity to bees. This study investigated the possible developmental toxicities as well as the acute toxicities of FIL, fipronil sulfide (FIL-SI), and fipronil sulfone (FIL-SO) to zebrafish (Danio rerio) embryos. At concentrations up to 5000 µg L-1, FIL- and FIL-SI-treated embryos exhibited significant mortality at 96 h postfertilization. Body length was significantly shortened with increasing concentrations in FIL- and FIL-SI-treated embryos. However, FIL-SO-treated embryos exhibited low mortality with high hatching rates. Body length was also significantly shortened in FIL-SO-treated embryos. Regarding the number of intersegmental vessels (ISVs), all chemical-treated embryos showed high ISV numbers with increasing concentrations of each chemical. FIL and FIL-SI induced abnormal heart formation with heart dysfunction in embryos, whereas FIL-SO did not induce any difference in heart development compared with the control. Abnormal heart formation may be related to the upregulation of nppa responsible for the expression of natriuretic peptides in embryos. Embryonic acetylcholinesterase activity was decreased gradually according to the increase in FIL and FIL-SI concentrations, whereas FIL-SO did not cause any change in enzyme activity. Il-1ß responsible for the occurrence of injury or infection was highly upregulated in FIL-SI- and FIL-SO-treated embryos. Therefore, reduction to FIL-SI may be associated with FIL toxicity, whereas oxidation to FIL-SO may be a detoxification route in the environment.

Piperlongumine treatment impacts heart and liver development and causes developmental delay in zebrafish (Danio rerio) embryos.

Piperlongumine (PL) and piperine (PP) are alkaloids presented in long pepper (Piper longum), and they exhibit various biological activities, especially anti-cancer properties. With these regards, they are considered as future medicines with high potential. Even they are exposed to humans such a long time, their potential toxicities in the environment have not been studied. Therefore, their ecological toxicities were assessed using zebrafish embryos. PP showed low mortality and no abnormal phenotype up to 10 µM. However, PL exhibited strong acute toxicity at the concentration of 5-10 µM ranges, and abnormal development were frequently found in the range of 1-2.5 µM with pericardial and yolk sac edemas. In transgenic zebrafish embryos, PL induced an increase in the number of intersegmental vessels and delayed the early-stage development. PL treatment affected heart formation and heart rate. The presence of PL induced the expression of cytokines, inflammatory markers, and inflammasome in the embryos. The PL treatment changed the mRNA levels of the ER stress and apoptosis-related genes. In addition, ROS production was observed during early-stage development of PL-treated zebrafish embryos. These results indicate that developing PL as a medicine would require extremely meticulous strategies to prevent potential toxicity.

Enantioselective effect of trifloxystrobin in early-stage zebrafish (Danio rerio) embryos: Cardiac abnormalities impacted by E,E-trifloxystrobin enantiomer.

Trifloxystrobin (TFS) is one of the extensively used strobilurin fungicides, which is composed of four enantiomers and its active form is E,E-TFS. In this study, we assess the acute toxicity of four enantiomers, E,E-, E,Z-, Z,E-, and Z,Z-TFS in zebrafish (Danio rerio) embryos. Among the four enantiomers, only E,E-TFS was found to be acutely toxic, with an estimated LC50 value of 0.68 mg/L. Treatment with E,E-TFS resulted in various phenotypic changes in the embryos, including pericardial and yolk-sac edema, spine curvature, and blood pooling. And it shortened the whole body length in the treated embryos by increasing the total intersegmental vessel numbers using a Tg(fli1a:EGFP) zebrafish line. Further study using Tg(cmlc2:EGFP) zebrafish line revealed that E,E-TFS treatment was associated with cardiac malformations, a failure of heart function, and a lowered heartbeat rate at the concentration of 0.25 mg/L. Also, the differential gene expression analysis identified significant down-regulation of vmhc and cacna1c genes encoding ventricular myosin heavy chain and calcium voltage-gated channel subunit alpha 1C, which are crucial for heart development. These results suggest the need for regular monitoring of E,E-TFS enantiomers after field application and further research into their potential chronic effects on environmental organisms.

Antimelanogenic Effects of Curcumin and Its Dimethoxy Derivatives: Mechanistic Investigation Using B16F10 Melanoma Cells and Zebrafish (Danio rerio) Embryos.

Regulation of melanin production via the MC1R signaling pathway is a protective mechanism of the skin of living organisms against exposure to ultraviolet rays. The discovery of human skin-whitening agents has been one of the most intense pursuits of the cosmetic industry. The MC1R signaling pathway is activated by its agonist, alpha-melanocyte stimulating hormone (α-MSH), and mainly regulates melanogenesis. Here, we evaluated the antimelanogenic activities of curcumin (CUR) and its two derivatives, dimethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), in B16F10 mouse melanoma cells and zebrafish embryos. CUR and BDMC reduced the α-MSH-induced melanin production in B16F10 cells and also downregulated the expression of the melanin-production-related genes Tyr, Mitf, Trp-1, and Trp-2. Moreover, the biological activity of these two compounds against melanogenesis was confirmed in in vivo experiments using zebrafish embryos. However, the highest concentration of CUR (5 µM) resulted in slight malformations in zebrafish embryos, as indicated by acute toxicity tests. In contrast, DMC did not show any biological activity in vitro or in vivo. Conclusively, BDMC is a strong candidate as a skin-whitening agent.

Combined toxicity of 3,5,6-trichloro-2-pyridinol and 2-(bromomethyl)naphthalene in the early stages of zebrafish (Danio rerio) embryos: Abnormal heart development at lower concentrations via differential expression of heart forming-related genes.

Combined toxicity can occur in the environment according to the combination of single substances, and the combination works additively or in a synergistic or antagonistic mode. In our study, 3,5,6-trichloro-2-pyridinol (TCP) and 2-(bromomethyl)naphthalene (2-BMN) were used to measure combined toxicity in zebrafish (Danio rerio) embryos. As the lethal concentration (LC) values were obtained through single toxicity, the lethal effects at all combinational concentrations were considered synergistic by the Independent Action model. At 96 hpf, the combined toxicity of TCP LC10 + 2-BMN LC10, the lowest combinational concentration, resulted in high mortality, strong inhibition of hatching, and various morphological changes in zebrafish embryos. Combined treatment resulted in the downregulation of cyp1a, leading to reduced detoxification of the treated chemicals in embryos. These combinations may enhance endocrine-disrupting properties via upregulation of vtg1 in embryos, and inflammatory responses and endoplasmic reticulum stress were found to upregulate il-ß, atf4, and atf6. These combinations might induce severe abnormal cardiac development in embryos via downregulation of myl7, cacna1c, edn1, and vmhc expression, and upregulation of the nppa gene. Therefore, the combined toxicity of these two chemicals was observed in zebrafish embryos, which proves that similar substances can exhibit stronger combined toxicity than single toxicity.

Developmental toxicity of a pymetrozine photo-metabolite, 3-pyridinecarboxaldehyde, in zebrafish (Danio rerio) embryos: Abnormal cardiac development and occurrence of heart dysfunction via differential expression of heart formation-related genes.

Pymetrozine (PYM) is worldwide used to control sucking insect pests in rice-cultivated fields and it is degraded into various metabolites including 3-pyridinecarboxaldehyde (3-PCA). These two pyridine compounds were used to determine their impacts on aquatic environments, particularly on the aquatic animal model zebrafish (Danio rerio). PYM did not show acute toxicities in terms of lethality, hatching rate, and phenotypic changes in zebrafish embryos in the tested ranges up to a concentration of 20 mg/L. 3-PCA exhibited acute toxicity with LC50 and EC50 values of 10.7 and 2.07 mg/L, respectively. 3-PCA treatment caused phenotypic changes including pericardial edema, yolk sac edema, hyperemia, and curved spine, at a concentration of 10 mg/L after 48 h of exposure. Abnormal cardiac development was observed in 3-PCA-treated zebrafish embryos at a concentration of 5 mg/L with reduced heart function. In a molecular analysis, cacna1c, encoding a voltage-dependent calcium channel, was significantly down-regulated in the 3-PCA-treated embryos, indicating synaptic and behavioral defects. Hyperemia and incomplete intersegmental vessels were observed in 3-PCA-treated embryos. Based on these results, it is necessary to generate scientific information on the acute and chronic toxicity of PYM and its metabolites with regular monitoring of their residues in aquatic environments.

Phosphine gas in the dark induces severe phytotoxicity in Arabidopsis thaliana by increasing a hypoxia stress response and disrupting the energy metabolism: Transcriptomic approaches.

Phosphine (PH3) is an ideal fumigant alternative on methyl bromide (MB) as MB has been classified as an ozone-depleting substance. However, several challenges limit its efficient use in crop production, including the emergence of PH3-resistant insect pests and the incidence of phytotoxic effects on nursery plants. Therefore, this study aims to elucidate the mechanism underlying PH3 phytotoxicity in plants using transcriptomic techniques. Fumigation with 2 g/m3 PH3 induced phytotoxic effects in A. thaliana, as evidenced by a decrease in growth and vegetation indices compared to the control group. Transcriptomic analysis revealed that PH3 fumigation phytotoxicity responses in A. thaliana involve genes related to hypoxia stress and energy metabolism. Additionally, pretreatment with ethylene induced pre-adaptation to hypoxia under light conditions during fumigation effectively suppressed the phytotoxic effects of PH3 in A. thaliana by increasing the expression of hypoxia-adaptive genes. Moreover, the phytotoxicity of PH3 was also confirmed in pumpkin (Cucurbita moschata Duch.), and was dependent on light. Overall, our findings showed that fumigation under light conditions and ethylene pretreatment could be used to minimize PH3-induced phytotoxic effects in plants.