Objective: Efficient management of cardiovascular diseases (CVDs) is an essential function of regional medical care systems. In this regard, the compatibility of cardiac biomarkers such as B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plays a crucial role. Patient/Materials and Methods: A total of 1,007 participants were included in this study. To make NT-proBNP more compatible with BNP levels, we examined alternative cutoff NT-proBNP levels derived by curve-fitting as well as formulas to convert NT-proBNP to BNP levels derived by multivariable linear regression analyses. Results: In comparison with alternative cutoffs or Formula #1, Formula #2, which included age, platelet count, and creatinine level as parameters, showed the best performance for improving the conformity between BNP and NT-proBNP levels. Using Formula #2, the concordance between BNP and NT-proBNP increased from 94.1% to 98.1% at a BNP cutoff of 40 pg/mL, and from 99.1% to 100.0% at a BNP cutoff of 100 pg/mL. Conclusions: The selection of NT-proBNP cutoffs corresponding to BNP cutoffs and the application of conversion formulas improved the concordance between BNP and NT-proBNP levels to nearly 100%, which would greatly contribute to the efficient management of CVDs in the regional medical care system.

The close association between obesity and type 2 diabetes, termed diabesity, is strongly linked to chronic low-grade inflammation. Rhamnan sulfate (RS), a sulfated polysaccharide derived from the edible green seaweed Monostroma nitidum, exhibits lipid-lowering and anti-inflammatory properties, but its effects on diabesity remain incompletely understood. Here, we evaluated the effects of dietary RS in a high-fat diet (HFD)-induced diabesity model using spontaneous type 2 diabetic mice. Oral RS (250 mg/kg/day for 10 weeks) resulted in lower final body weight compared with HFD controls (48.2 ± 4.7 g vs. 53.5 ± 1.6 g, p < 0.05) and improved dyslipidemia, as indicated by decreased plasma triglyceride and total cholesterol levels. RS also led to improvements in hyperglycemia and hyperinsulinemia in HFD-fed mice. RNA-seq across brown adipose tissue, liver, and skeletal muscle revealed modulation of inflammation-related pathways, which was supported by qPCR validation. RS also suppressed pro-inflammatory gene expression in LPS-stimulated macrophages. These findings suggest that dietary RS is associated with reduced diabesity-related metabolic abnormalities and with modulation of inflammation across multiple tissues, highlighting its potential as a functional food ingredient.

Abstract Globin digest (GD), an acidic protease hydrolysate of hemoglobin, has been recognized for its anti-obesity and glucose-modulating effects; however, its direct anabolic potential in skeletal muscle remains uncharacterized. We evaluated the effects of GD and its constituent peptides on muscle hypertrophy and motor function using zebrafish, mice, and C2C12 myoblasts. Adult zebrafish administered GD (400 mg/kg BW/d) for 1 week showed significantly increased swimming distance ( p < 0.05). Similarly, oral administration of GD (1 g/kg BW/d) to C57BL/6J mice for 4 weeks enhanced grip strength and rotarod performance, accompanied by a 1.5-fold increase in myofiber diameter and upregulation of fast-twitch Myh1 (1.9-fold) and Myh2 (1.8-fold) mRNA levels. In vitro , GD dose-dependently (1–100 μg/mL) stimulated C2C12 differentiation and MyHC accumulation. Notably, GD did not merely serve as a nutritional nitrogen source; instead, it functioned as a signaling modulator via a specific “relay-like” peptide orchestration. Among six identified sequences, Peptides 3 (WTQR) and 5 (WGK) primarily initiated early-stage commitment by upregulating MyoD and Myf5 , whereas Peptides 2 (VVYP) and 6 (FES) accelerated mid-stage maturation. This stage-specific synergy achieved robust myotube hypertrophy that exceeded the efficacy of individual components. These findings demonstrate that GD promotes skeletal muscle hypertrophy and motor function through direct myogenic signaling, establishing a novel foundation for precision sports nutrition to optimize muscle maintenance and physical performance.

Ultraviolet B (UVB) irradiation induces epidermal dysregulation characterized by hyperpigmentation, barrier dysfunction, and abnormal keratinocyte differentiation, contributing to photoaging and skin disorders. Ceramides are key structural lipids of the stratum corneum and are widely used as topical agents to support barrier integrity. However, the role of oral ceramide in UVB-induced skin damage remains unclear. In this study, we investigated whether oral ceramide administration attenuates UVB-induced skin alterations in HRM-2 hairless mice. Mice were repeatedly exposed to UVB and orally administered ceramide (2.5 or 7.5 mg/kg/day). UVB exposure increased dorsal skin pigmentation, epidermal thickness, microphthalmia-associated transcription factor (MITF) expression, and melanogenesis-related gene transcription, while tending to reduce skin hydration. Oral ceramide markedly suppressed these changes and enhanced skin moisture content without affecting general health status. Immunofluorescence and reverse transcription-quantitative PCR analyses revealed a reduction in the number of MITF-positive cells and downregulation of Tyrp1, Mc1r, and Mitf. RNA sequencing analysis further demonstrated that ceramide counteracted UVB-induced transcriptional dysregulation by suppressing keratinization pathways and promoting retinoic acid receptor- and wound-healing-associated signaling. These findings indicate that oral ceramide not only reduces melanin synthesis but also promotes the recovery of epidermal homeostasis by modulating melanocyte activity, keratinocyte differentiation, and barrier function. Accordingly, oral ceramide attenuates UVB-induced skin pigmentation by suppressing MITF-dependent melanogenesis and restoring skin homeostasis, highlighting its potential as a therapeutic agent for photodamage-associated skin disorders.

Zebrafish are model organisms for drug screening owing to their transparent bodies, rapid embryonic development, and genetic similarities with humans. However, using standard polystyrene culture plates can limit the oxygen supply, potentially affecting embryo survival and the reliability of assays conducted in zebrafish. In this study, we evaluated the application of a novel, highly oxygen-permeable culture plate (InnoCellTM) in zebrafish development and drug screening assays. Under both normal and oxygen-restricted conditions, zebrafish embryos cultured on InnoCellTM plates exhibited significantly improved developmental parameters, including heart rate and body length, compared with those cultured on conventional polystyrene plates. The InnoCellTM plate enabled a significant reduction in medium volume without compromising zebrafish embryo viability, thereby demonstrating its advantages, particularly in high-throughput 384-well formats. Drug screening tests using antiangiogenic receptor tyrosine kinase inhibitors (TKIs) revealed enhanced sensitivity and more pronounced biological effects in InnoCellTM plates, as evidenced by the quantification of intersegmental blood vessels and gene expression analysis of the vascular endothelial growth factor receptor (vegfr, also known as kdrl). These results indicate that the InnoCellTM highly oxygen-permeable plate markedly improves zebrafish-based drug screening efficiency and assay reliability, highlighting its potential for widespread application in biomedical research.

Anemia, characterized by reduced hemoglobin (Hb), remains a major health concern. Although iron and erythropoietin (EPO) therapies are effective, limitations in safety and accessibility have prompted interest in nutritional alternatives. Hydrolyzed milk-derived peptides (H-MDPs) contain bioactive sequences with diverse physiological effects, yet their role in erythropoiesis remains poorly defined. This study investigated the hematopoietic actions of H-MDP using zebrafish and mouse models. Adult zebrafish underwent phlebotomy-induced anemia and received oral H-MDP for 3 weeks. Hb levels, erythrocyte morphology, and expression of erythropoiesis- and iron-metabolism genes were assessed. In healthy mice, renal Epo expression, circulating EPO, and serum cytokines were measured after 2 weeks of H-MDP administration. H-MDP significantly accelerated Hb recovery in anemic zebrafish (4.6 ± 0.64 g/dL vs. 3.4 ± 0.66 g/dL in untreated fish at week 1) and markedly improved erythrocyte maturation. These effects coincided with strong induction of epo, hif1aa/b, igf1, csf1a, and csf3b in the heart and liver, as well as normalization of anemia-induced hepatic iron-transport genes (tfa, fpn1, tfr2) and reactivation of hamp. In mice, H-MDP elevated renal Epo mRNA and circulating EPO (approximately 2.3-fold) without altering steady-state Hb, and cytokine profiling with IPA-predicted activation of the erythropoietin signaling pathway. Collectively, these findings indicate that H-MDPs modulate erythropoiesis by coordinating the activation of EPO-related and iron-regulatory networks, supporting their potential as functional food ingredients for hematologic recovery and anemia management.

Abstract Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as Monostroma nitidum that exhibits various biological functions, including anticoagulant, antitumour, antiviral, and anti‐obesity properties. In our previous clinical trial, we demonstrated that RS intake improves constipation. However, no specific bacteria showed a significant (p < .05) change. Notably, these results were obtained after a short RS inoculation period of only 2 weeks. In the present study, to evaluate the long‐term effects of RS on the gut microbiota, we orally administered RS to BALB/c mice for 11 weeks, analyzed their blood biochemical data, and performed 16s rRNA‐sequencing. Oral administration of RS increased body weight with increased food intake, whereas plasma total cholesterol and fasting plasma glucose levels decreased. RS‐fed mice showed lower fasting insulin levels (p < .1) and decreased homeostatic model assessment for insulin resistance (HOMA‐IR, p < .0001), suggesting that RS improved insulin resistance. In the feces of mice, the amounts of acetic and propionic acids increased. In the gut microbiota, predictive metagenomic profiling using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) revealed functional alterations in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways in RS‐fed mice. Corresponding to the blood glucose‐lowering effect, the glycolysis and tricarboxylic acid (TCA) cycle pathways were activated. In addition, the Firmicutes/Bacteroides (F/B) ratio, which may be associated with various health outcomes, was also reduced. These results suggest that the blood glucose‐lowering effect, improvement in insulin resistance, and lipid‐lowering effect of RS may be due to changes in the intestinal microbiota.

Diabetic nephropathy (DN), as a complication of diabetes, is a substantial healthcare challenge owing to the high risk of morbidity and mortality involved. Although significant progress has been made in understanding the pathogenesis of DN, more efficient models are required to develop new therapeutics. Here, we created a DN model in zebrafish by crossing diabetic Tg(acta1:dnIGF1R-EGFP) and proteinuria-tracing Tg(l-fabp::VDBP-GFP) lines, named zMIR/VDBP. Overfed adult zMIR/VDBP fish developed severe hyperglycemia and proteinuria, which were not observed in wild -type zebrafish. Renal histopathology revealed human DN-like characteristics, such as glomerular basement membrane thickening, foot process effacement and glomerular sclerosis. Glomerular dysfunction was restored upon calorie restriction. RNA sequencing analysis demonstrated that DN zebrafish kidneys exhibited transcriptional patterns similar to those seen in human DN pathogenesis. Notably, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated, a phenomenon observed in the early phase of human DN. In addition, metformin improved hyperglycemia and proteinuria in DN zebrafish by modulating Akt phosphorylation. Our results indicate that zMIR/VDBP fish are suitable for elucidating the mechanisms underlying human DN and could be a powerful tool for therapeutic discovery.

Obesity is an emerging global health issue with an increasing risk of disease linked to lifestyle choices. Previously, we reported that the hexane extract of Citrus sphaerocarpa (CSHE) suppressed lipid accumulation in differentiated 3T3-L1 adipocytes. In this study, we conducted in vivo experiments to assess whether CSHE suppressed obesity in zebrafish and mouse models. We administered 10 and 20 μg/mL CSHE to obese zebrafish juveniles. CSHE significantly inhibited visceral fat accumulation compared to untreated obese fish. Moreover, the oral administration (100 μg/g body weight/day) of CSHE to high-fat-diet-induced obese mice significantly reduced their body weight, visceral fat volume, and hepatic lipid accumulation. The expression analyses of key regulatory genes involved in lipid metabolism revealed that CSHE upregulated the mRNA expression of lipolysis-related genes in the mouse liver (Pparα and Acox1) and downregulated lipogenesis-related gene (Fasn) expression in epididymal white adipose tissue (eWAT). Fluorescence immunostaining demonstrated the CSHE-mediated enhanced phosphorylation of AKT, AMPK, ACC, and FoxO1, which are crucial factors regulating adipogenesis. CSHE-treated differentiated 3T3L1 adipocytes also exhibited an increased phosphorylation of ACC. Therefore, we propose that CSHE suppresses adipogenesis and enhances lipolysis by regulating the PI3K/AKT/FoxO1 and AMPK/ACC signaling pathways. These findings suggested that CSHE is a promising novel preventive and therapeutic agent for managing obesity.

Yokkaichi is one of the four major Japanese cities facing air pollution after World War II, owing to modern urban industrialization in the 20th century. Tianjin City, in China, also showed similar industrial patterns in the petrochemical industry. For decades, the petrochemical industry development has been deteriorating the environment with its by-product, sulfur dioxide (SO2). In this paper, we summarized the characteristics of air pollution in Yokkaichi through a retrospective approach by comparing common features of Yokkaichi and Tianjin. We believe that Yokkaichi is at Stage 4, after the pollution stage, whereas Tianjin is currently in Stage 3. We believe that the efficacy of regional environmental policies in Yokkaichi related to SO2 pollution can help predict the pollution pattern in Tianjin. We used an extended stochastic regression on a population, affluence, and technology model as a reference to demonstrate the feasibility of Yokkaichi's pattern and the comparison between Yokkaichi and Tianjin. Fossil fuels, especially crude oil, may continuously be exploited as the main energy source in the next few decades. Thus, experiences of SO2 air pollution in Yokkaichi and Tianjin's could be of universal value. As it has been 50 years since the final judgment of the Yokkaichi Asthma and Yokkaichi Air pollution joint lawsuit, we attempted to reflect on Yokkaichi's history to strengthen efforts to achieve future sustainable development goals.

Metabolic syndrome comprises a group of conditions that collectively increase the risk of abdominal obesity, diabetes, atherosclerosis, cardiovascular diseases, and cancer. Gut microbiota is involved in the pathogenesis of metabolic syndrome, and microbial diversity and function are strongly affected by diet. In recent years, epidemiological evidence has shown that the dietary intake of seaweed can prevent metabolic syndrome via gut microbiota modulation. In this review, we summarize the current in vivo studies that have reported the prevention and treatment of metabolic syndrome via seaweed-derived components by regulating the gut microbiota and the production of short-chain fatty acids. Among the surveyed related articles, animal studies revealed that these bioactive components mainly modulate the gut microbiota by reversing the Firmicutes/Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria, such as Bacteroides, Akkermansia, Lactobacillus, or decreasing the abundance of harmful bacteria, such as Lachnospiraceae, Desulfovibrio, Lachnoclostridium. The regulated microbiota is thought to affect host health by improving gut barrier functions, reducing LPS-induced inflammation or oxidative stress, and increasing bile acid production. Furthermore, these compounds increase the production of short-chain fatty acids and influence glucose and lipid metabolism. Thus, the interaction between the gut microbiota and seaweed-derived bioactive components plays a critical regulatory role in human health, and these compounds have the potential to be used for drug development. However, further animal studies and human clinical trials are required to confirm the functional roles and mechanisms of these components in balancing the gut microbiota and managing host health.

Oral administration of rhamnan sulfate (RS), derived from the seaweed Monostroma nitidum, markedly suppresses inflammatory damage in the vascular endothelium and organs of lipopolysaccharide-treated mice. This study aimed to analyze whether orally administered RS inhibits the development of atherosclerosis, a chronic inflammation of the arteries. ApoE-deficient female mice were fed a normal or high-fat diet (HFD) with or without RS for 12 weeks. Immunohistochemical and mRNA analyses of atherosclerosis-related genes were performed. The effect of RS on the migration of RAW264.7 cells was also examined in vitro. RS administration suppressed the increase in blood total cholesterol and triglyceride levels. In the aorta of HFD-fed mice, RS reduced vascular smooth muscle cell proliferation, macrophage accumulation, and elevation of VCAM-1 and inhibited the reduction of Robo4. Increased mRNA levels of Vcam1, Mmp9, and Srebp1 in atherosclerotic areas of HFD-fed mice were also suppressed with RS. Moreover, RS directly inhibited the migration of RAW264.7 cells in vitro. Thus, in HFD-fed ApoE-deficient mice, oral administration of RS ameliorated abnormal lipid metabolism and reduced vascular endothelial inflammation and hyperpermeability, macrophage infiltration and accumulation, and smooth muscle cell proliferation in the arteries leading to atherosclerosis. These results suggest that RS is an effective functional food for the prevention of atherosclerosis.

To reduce the local scour around pier-type structures, a "porous plate method" was proposed, aiming at effectiveness in multidirectional horizontal flows. The porous plates installed on the pier surface near the bed play two important roles in the reduction of the local scour. One is "breaking down or weakening" of the horseshoe vortex by a decline in vorticity. In the neighborhood (just upstream region), the local scour depth greatly decreases due to suppression of picking up sediment grains from the bed. Another is the resultant "flow regulation" in the boundary layer on the pier surface. In the downstream side, the wake separated from the pier surface behaves as "semi-homogeneous turbulence" without a Karman vortex street, then the scour area drastically decreases.

EDITORIAL article Front. Cell Dev. Biol., 11 March 2022Sec.Molecular and Cellular Pathology https://doi.org/10.3389/fcell.2022.861941

Numerous reports on the occurrence of microplastics/nanoplastics (MP/NP) in aquatic environments have triggered severe concerns about the adverse impact of these particles on aquatic organisms and their transfer through food webs. The past few years have seen an emerging interest among toxicologists in the use of omics technologies to elucidate the response of fish and other aquatic organisms to environmental contaminants. Omics approaches, such as transcriptomics, proteomics, microbiomics, and metabolomics, have advanced our knowledge of MP/NP-related toxicity. The integration of multi-omics provides a deeper understanding of the toxicity mechanisms and pathways involved. This review provides comprehensive updates and status on applying omics technologies to study the MP/NP-related toxicity in fish and seafood species. Compared with other toxicants, the signature profile or finger-print of MP/NP still requires further development. Further, a robust regulatory oversight is required to monitor and minimise MP/NP contamination in commercially-important aquatic species. (c) 2022 Elsevier B.V. All rights reserved.

[Background] The obesity epidemic has been drastically progressing in both children and adults worldwide. Pharmacotherapy is considered necessary for its treatment. Because many anti-obesity drugs have been withdrawn from the market due to their adverse effects, the development of new drugs is still needed. Zebrafish are ideal model animals for in vivo testing of anti-obesity compounds, and disease models of several types of obesity have been developed.

The ubiquity of microplastic/nanoplastics (MP/NPs) provides an opportunity for their interaction with other widely spread environmental contaminants. MP/NP and nanoparticles share a similar transport route from sources, production, and disposal. Metal oxide nanoparticles (nMOx) have varied industrial applications, and limited knowledge is available on their interaction with MP/NPs. The present study investigated the effect of NPs (1 mg/L) on the efflux of two nMOx, aluminium oxide nanoparticles (nAl2O3, 1 mg/L) and cerium oxide nanoparticles (nCeO2, 1 mg/L), and their combined toxicity to zebrafish embryos. The results illustrated increased accumulation of aluminium and cerium in the combined exposure group compared to the nMOx alone treatment. The presence of NPs exacerbated the oxidative stress caused by nAl2O3 and nCeO2, as evidenced by an increase in the concentration of reactive oxygen species (ROS), alteration of antioxidants, and lipid peroxidation. The integrated biomarker response (IBRv2) values showed the induction of an antioxidative response in NP + nAl2O3, whereas a decline in IBRv2 values was observed in NP + nCeO2. Our results indicate that NPs aggravated the accumulation of nMOx and their toxicity. The present work highlights that more attention should be paid to the discharge of these contaminants into the natural environment.

Water disinfection is one of the most important applications of ultraviolet light-emitting diodes (UV-LEDs), though bacterial regrowth remains a serious problem. In this study, we showed that UV-resistant cells, though rare, exist in an Escherichia coli clonal population. The UV-resistance of stationary phase cells was higher than that of exponential phase cells. Regrowth cell populations showed identical UV sensitivity before and after UV treatment, indicating that UV resistance is not acquired genetically, but is generated stochastically. The characteristics of these UV-resistant cells are similar to those of non-heritable antibiotic-resistant cells, termed persisters. The induction of persister formation increased the number of viable cells after UV treatment. The toxin-antitoxin system gene hipA (high persistence A) is a key factor in persister cell formation. We observed that hipA was strongly expressed in the stationary phase cells, while regrowth cells after UV treatment lost hipA expression, suggesting that the regrowth cells lost their persistence. Compared to UV batch radiation, we demonstrated that intermittent UV irradiation, which included the induction of regrowth between UV treatments, significantly reduced the number of viable E. coli cells.

AbstractThe zebrafish obesogenic test (ZOT) is a powerful tool for identifying anti‐adipogenic compounds for in vivo screening. In our previous study, we found that Moringa oleifera (MO) leaf powder suppressed the accumulation of visceral adipose tissue (VAT) in ZOT. MO demonstrates a wide range of pharmacological effects; however, little is known about its functional constituents. To identify the anti‐adipogenic components of MO leaves, we prepared extracts using different extraction methods and tested the obtained extracts and fractions using ZOT. We found that the dichloromethane extract and its hexane:EtOAc = 8:2 fraction reduced VAT accumulation in young zebrafish fed a high‐fat diet. We also performed gene expression analysis in the zebrafish VAT and found that CCAAT/enhancer‐binding protein beta and CCAAT/enhancer‐binding protein delta (associated with early stages of adipogenesis) gene expression was downregulated after fraction 2 administration. We identified a new MO fraction that suppressed VAT accumulation by inhibiting early adipogenesis using the ZOT. Phenotype‐driven zebrafish screening is a reasonable strategy for identifying bioactive components in natural products.

Ultraviolet (UV) rays can be both harmful and beneficial to humans. This study aimed to investigate the toxicity and safety of ultraviolet C (UVC) exposure in living organisms and the corresponding biodefense molecular mechanisms. Zebrafish embryos, at an early developmental stage (5-6 h post-fertilization), were irradiated with increasing UVC dosages using high-efficiency deep-ultraviolet light-emitting diodes (278 nm). Morphological phenotypes including survival rate, hatching rate, heart rate, and malformation rate were evaluated. Compared to un-irradiated controls, all zebrafish embryos exposed to 4.5 mJ/cm2 UVC survived and showed no significant difference in hatching and heart rate. However, 7.5 mJ/cm2 of UVC irradiation caused a significantly decreased survival rate (37.5%) and an increased malformation rate (81.8%). Therefore, 4.5 mJ/cm2 was chosen as the limit dosage that the internal biodefense system of zebrafish embryos can protect against UVC radiation. Transcriptome analysis (RNA sequencing) performed on 3 min and 3 days post-irradiation embryos (4.5 mJ/cm2) revealed the molecular mechanisms underlying the response of zebrafish embryos to irradiation. The embryos quickly responded to UVC-induced stress by activating the p53 signaling pathway. In addition, after 3 days of recuperation, the embryos showed activation of signal transducer and activator of transcription (STAT) signaling pathway. To our knowledge, this is the first study to evaluate the toxicological effects and the molecular mechanism of biodefense in zebrafish embryos upon 278 nm UVC irradiation.