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33 pages, 452 KiB  
Review
Uncommon Factors Leading to Nephrotic Syndrome
by Ljiljana Bogdanović, Ivana Babić, Mirjana Prvanović, Dragana Mijač, Ana Mladenović-Marković, Dušan Popović and Jelena Bogdanović
Biomedicines 2025, 13(8), 1907; https://doi.org/10.3390/biomedicines13081907 - 5 Aug 2025
Abstract
Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge [...] Read more.
Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article
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19 pages, 10865 KiB  
Article
Evaluation of Immunoprotective Activities of White Button Mushroom (Agaricus bisporus) Water Extract Against Major Pathogenic Bacteria (Aeromonas hydrophila or Vibrio fluvialis) in Goldfish (Carassius auratus)
by Shujun Sun, Jing Chen, Pan Cui, Xiaoxiao Yang, Yuhan Zheng, Zijian Ma, Yong Liu and Xiang Liu
Animals 2025, 15(15), 2257; https://doi.org/10.3390/ani15152257 - 1 Aug 2025
Viewed by 168
Abstract
The white button mushroom (Agaricus bisporus) is a widely cultivated edible and medicinal mushroom, which contains various active substances, and has application value against pathogenic bacteria in aquaculture. Firstly, A. bisporus water extract (AB-WE) was prepared. Through the detection kits, it [...] Read more.
The white button mushroom (Agaricus bisporus) is a widely cultivated edible and medicinal mushroom, which contains various active substances, and has application value against pathogenic bacteria in aquaculture. Firstly, A. bisporus water extract (AB-WE) was prepared. Through the detection kits, it was found that the polysaccharide, protein, and polyphenol components of AB-WE were 9.11%, 3.3%, and 1.5%, respectively. The 246 compounds were identified in AB-WE, and the major small-molecule components included L-Isoleucine, L-Tyrosine, L-Valine, and Linoleic acid by HPLC-Q Exactive-Orbitrap-MS. Secondly, the AB-WE was evaluated for its immunological activities through dietary administration and pathogen challenge (Aeromonas hydrophila and Vibrio fluvialis) in goldfish (Carassius auratus). The results showed that the levels of immune factors of acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM) increased (p < 0.05) in goldfish, and the relative percentage survival of AB-WE against A. hydrophila and V. fluvialis were 80.00% (p < 0.05) and 81.82% (p < 0.05), respectively. The AB-WE reduced the bacterial content in renal tissue, enhanced the phagocytic activity of leukocytes, and exhibited antioxidant and anti-inflammatory effects by reducing the expression of antioxidant-related factors and inflammatory factors. Through histopathological and immunofluorescence techniques, it was found that AB-WE maintained the integrity of visceral tissues and reduced renal tissue apoptosis and DNA damage. Therefore, AB-WE exhibits immunoprotective activity against A. hydrophila and V. fluvialis infections in fish, and holds promise as an immunotherapeutic agent against major pathogenic bacteria in aquaculture. Full article
(This article belongs to the Section Aquatic Animals)
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24 pages, 6731 KiB  
Article
Combined Impacts of Acute Heat Stress on the Histology, Antioxidant Activity, Immunity, and Intestinal Microbiota of Wild Female Burbot (Lota Lota) in Winter: New Insights into Heat Sensitivity in Extremely Hardy Fish
by Cunhua Zhai, Yutao Li, Ruoyu Wang, Haoxiang Han, Ying Zhang and Bo Ma
Antioxidants 2025, 14(8), 947; https://doi.org/10.3390/antiox14080947 (registering DOI) - 31 Jul 2025
Viewed by 305
Abstract
Temperature fluctuations caused by climate change and global warming pose a threat to fish. The burbot (lota lota) population is particularly sensitive to increased water temperature, but the systematic impacts of high-temperature exposure on their liver and intestinal health remain unclear. [...] Read more.
Temperature fluctuations caused by climate change and global warming pose a threat to fish. The burbot (lota lota) population is particularly sensitive to increased water temperature, but the systematic impacts of high-temperature exposure on their liver and intestinal health remain unclear. In January of 2025, we collected wild adult burbot individuals from the Ussuri River (water temperature: about 2 °C), China. The burbot were exposed to 2 °C, 7 °C, 12 °C, 17 °C, and 22 °C environments for 96 h; then, the liver and intestinal contents were subsequently collected for histopathology observation, immunohistochemistry, biochemical index assessment, and transcriptome/16S rDNA sequencing analysis. There was obvious liver damage including hepatocyte necrosis, fat vacuoles, and cellular peripheral nuclei. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were elevated and subsequently decreased. Additionally, the malondialdehyde (MDA) level significantly increased with increasing temperature. These results indicate that 7 °C (heat stress temperature), 12 °C (tipping point for normal physiological metabolism status), 17 °C (tipping point for individual deaths), and 22 °C (thermal limit) are critical temperatures in terms of the physiological response of burbot during their breeding period. In the hepatic transcriptome profiling, 6538 differentially expressed genes (DEGs) were identified, while KEGG enrichment analysis showed that high-temperature stress could affect normal liver function by regulating energy metabolism, immune, and apoptosis-related pathways. Microbiomics also revealed that acute heat stress could change the intestinal microbe community structure. Additionally, correlation analysis suggested potential regulatory relationships between intestinal microbe taxa and immune/apoptosis-related DEGs in the liver. This study revealed the potential impact of environmental water temperature changes in cold habitats in winter on the physiological adaptability of burbot during the breeding period and provides new insights for the ecological protection of burbot in the context of global climate change and habitat warming. Full article
(This article belongs to the Special Issue Antioxidant Response in Aquatic Animals)
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15 pages, 1262 KiB  
Article
Bycatch in Cetaceans from the North-Western Mediterranean Sea: Retrospective Study of Lesions and Utility of Bycatch Criteria
by Laura Martino, Mariona Leiva Forns, Marina Cid Cañete, Lola Pérez, Cèlia Pradas and Mariano Domingo
Vet. Sci. 2025, 12(8), 711; https://doi.org/10.3390/vetsci12080711 - 29 Jul 2025
Viewed by 565
Abstract
Bycatch is the most common cause of death of small delphinids worldwide, including the Mediterranean Sea. The diagnosis of bycatch as cause of death in stranded cetaceans depends on the cumulative presence of multiple findings, termed bycatch criteria. In this study, we retrospectively [...] Read more.
Bycatch is the most common cause of death of small delphinids worldwide, including the Mediterranean Sea. The diagnosis of bycatch as cause of death in stranded cetaceans depends on the cumulative presence of multiple findings, termed bycatch criteria. In this study, we retrospectively evaluated the presence of bycatch criteria in 138 necropsied cetaceans, 136 stranded and 2 confirmed bycaught, in the Catalan Mediterranean Sea across a 13-year period. With the aim of identifying the most specific and reliable bycatch criteria, the animals’ cause of death was classified as either bycaught or other causes. Animals were necropsied according to standard procedures with complete histopathological examination and ancillary diagnostic techniques. We reviewed the necropsy reports and photographs of 138 cetaceans of seven species. Bycatch had been determined as the cause of death/stranding in 40 (29%) necropsied cetaceans. Both sexes were equally represented in the bycatch group. Bycatch was diagnosed in the Mediterranean common bottlenose dolphin (10/14; 71.4%), striped dolphin (29/108; 26.9%), and Risso’s dolphin (1/11; 9.1%). Sixty-seven out of 98 (68.3%) cetaceans that had been classified as non-bycatch had one or two bycatch criteria. Cetaceans with two and three major criteria had an overlap of causes of death, as some animals were diagnosed with bycatch and others with other causes of mortality. Animals with four criteria were invariably diagnosed as being bycaught. Recent feeding, absence of disease, good nutritional status, marks of fishing gear, multiorgan intravascular gas bubbles, hyphema and amputations or sharp incisions presumably inflicted by humans were significantly more likely to result in a diagnosis of bycatch, while loss of teeth and cranial fractures were not. None of the dolphins diagnosed as bycatch had ingested fishing gear. Our results highlight the relevance of bycatch as the cause of death of dolphins in the Mediterranean and suggest that some criteria traditionally linked to bycatch are not specific for bycatch in our region. Full article
(This article belongs to the Special Issue Pathology of Marine Large Vertebrates)
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25 pages, 5317 KiB  
Article
High Temperature and Ethinylestradiol May Reduce Body Growth, Liver and Hepatocyte Volumes and Lipid Droplets in Adult Male Guppies
by Margarida Vilaça, Sukanlaya Tantiwisawaruji, Maria João Rocha and Eduardo Rocha
Animals 2025, 15(14), 2152; https://doi.org/10.3390/ani15142152 - 21 Jul 2025
Viewed by 246
Abstract
Global warming raises surface water temperatures, impacting fish alongside pollutants, such as ubiquitous xenoestrogens. Combined stressor effects are poorly studied but likely to worsen impacts and hinder biota adaptation, warranting further research. Unadapted fish face heightened risks. The liver is a vital metabolic [...] Read more.
Global warming raises surface water temperatures, impacting fish alongside pollutants, such as ubiquitous xenoestrogens. Combined stressor effects are poorly studied but likely to worsen impacts and hinder biota adaptation, warranting further research. Unadapted fish face heightened risks. The liver is a vital metabolic organ, sensitive to temperature and xenoestrogens, eventually adjusting hepatocyte size and number to ensure survival, growth, and reproduction. This study assessed, for the first time, the impact of exposure (45 days) to thermal stress (29 °C versus 26 °C) and ethinylestradiol (EE2, 5 ng/L) on male guppies, primarily on body and quantitative liver morphology. Higher temperature reduced body mass (14%) and standard length (3.6%) gain. EE2 exposure reduced body mass increase (14%), hepatosomatic index (20%), and the volumes of the liver (32%), hepatocytes (16%), and their nuclei (17%). The nucleus-to-cytoplasm ratio and total hepatocyte number remained stable. No histopathological lesions existed. Guppies appear to have adapted to stressors by reducing hepatocyte size and utilizing lipid reserves, yet they exhibited deficits in body growth and hepatosomatic index. Gonadal maturation was unaffected. Only under EE2 at 29 °C did hepatocytes show minimal lipid droplet content (less vacuolation). This indicated exhausted reserves, reinforcing how heat and toxicants interact to exacerbate impacts. Full article
(This article belongs to the Section Aquatic Animals)
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23 pages, 4493 KiB  
Article
Low-Temperature Stress-Induced Hepatic Injury in Darkbarbel Catfish (Pelteobagrus vachelli): Mediated by Gut–Liver Axis Dysregulation
by Amei Liu, Guoqing Duan, Libo Yang, Yuting Hu, Huaxing Zhou and Huan Wang
Antioxidants 2025, 14(7), 762; https://doi.org/10.3390/antiox14070762 - 21 Jun 2025
Viewed by 553
Abstract
Low-temperature stress serves as a critical abiotic stressor that severely restricts fish survival, biogeographic distribution, and aquaculture productivity. Pelteobagrus vachelli, an economically significant freshwater fish species, displays marked sensitivity to low-temperature stress; however, its molecular adaptive mechanisms remain poorly characterized. In this [...] Read more.
Low-temperature stress serves as a critical abiotic stressor that severely restricts fish survival, biogeographic distribution, and aquaculture productivity. Pelteobagrus vachelli, an economically significant freshwater fish species, displays marked sensitivity to low-temperature stress; however, its molecular adaptive mechanisms remain poorly characterized. In this study, we systematically investigated hepatic and intestinal cold stress responses in P. vachelli through a 7-day acute low-temperature exposure trial (6 °C and 11 °C), integrating histopathological examination, physiological–biochemical assays, metabolomics, and 16S rRNA sequencing. Histopathological observations revealed pronounced hepatic vacuolar degeneration, nuclear dissolution, and enhanced inflammatory cell infiltration under low-temperature conditions. Concurrently, immune-related enzymatic activities—including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (APK)—were significantly elevated. Furthermore, substantial perturbations in antioxidant defense systems were detected, as indicated by altered superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, alongside malondialdehyde (MDA) accumulation. Metabolomic profiling identified 539 differentially abundant metabolites, with pathway enrichment analysis highlighting marked alterations in FoxO signaling, amino acid metabolism, glycerophospholipid metabolism, ABC transporter, and Purine metabolism. Gut microbiome sequencing demonstrated cold-induced structural dysbiosis within the intestinal microbiota. Correlation analyses revealed robust linkages between hepatic injury biomarkers/metabolites and specific intestinal microbial taxa. Collectively, this study delineates the interplay between hepatic metabolic reprogramming and gut microbiota dysbiosis during cold adaptation in P. vachelli, establishing a theoretical framework for developing gut–liver axis-targeted strategies to augment cold tolerance in aquatic species. Full article
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25 pages, 2638 KiB  
Article
Kidneys Under Siege: Pesticides Impact Renal Health in the Freshwater Fish Common Carp (Cyprinus carpio Linnaeus, 1758)
by Stela Stoyanova, Elenka Georgieva, Eleonora Kovacheva, László Antal, Dóra Somogyi, Ifeanyi Emmanuel Uzochukwu, László Nagy, Krisztián Nyeste and Vesela Yancheva
Toxics 2025, 13(7), 518; https://doi.org/10.3390/toxics13070518 - 20 Jun 2025
Viewed by 1692
Abstract
This study evaluated the histopathological impact of three commonly used pesticides—pirimiphos-methyl, propamocarb hydrochloride, and 2,4-dichlorophenoxyacetic acid (2,4-D)—on the kidneys of common carp (Cyprinus carpio Linnaeus, 1758) after 96-h acute exposure. The histopathological analysis demonstrated that all three tested pesticides induced structural changes. [...] Read more.
This study evaluated the histopathological impact of three commonly used pesticides—pirimiphos-methyl, propamocarb hydrochloride, and 2,4-dichlorophenoxyacetic acid (2,4-D)—on the kidneys of common carp (Cyprinus carpio Linnaeus, 1758) after 96-h acute exposure. The histopathological analysis demonstrated that all three tested pesticides induced structural changes. The histopathological changes were assessed using a semi-quantitative scoring system and categorised into circulatory, degenerative, proliferative, and inflammatory alterations. While circulatory alterations were absent in all treatments, clear and statistically significant degenerative, proliferative, and inflammatory responses were recorded, which escalated with increasing pesticide concentrations. Additionally, various statistical analyses were conducted to evaluate the lesions in kidney structure and function. Before the statistical analysis, normality and variance homogeneity were assessed using the Shapiro–Wilk and Levene’s tests, respectively. Due to non-normal data distribution, non-parametric methods were applied. Hence, the non-parametric statistical methods showed distinct group-level differences in the kidney damage indices. The Kruskal–Wallis test revealed significant differences across treatments (p < 0.001), and Mann–Whitney U tests identified specific pairwise differences. The degenerative and proliferative lesions were most prominent in fish exposed to 2,4-D at 100 µg/L (IK = 34), followed by pirimiphos-methyl and propamocarb hydrochloride. Inflammatory changes were mainly observed in the pirimiphos-methyl groups. The histopathological lesions were concentration-dependent, with 2,4-D causing irreversible renal damage at higher concentrations. These findings highlight the nephrotoxic risks posed by common pesticides and validate that the use of histopathological indices, combined with robust non-parametric testing, provides a reliable approach to evaluating organ-specific pesticide toxicity. These biomarkers offer sensitive early warning indicators of environmental risk, reinforcing the suitability of common carp as a model species for ecotoxicological assessment. Full article
(This article belongs to the Section Agrochemicals and Food Toxicology)
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13 pages, 5517 KiB  
Article
Subchronic Exposure to Microcystin-LR Induces Hepatic Inflammation, Oxidative Stress, and Lipid Metabolic Disorders in Darkbarbel Catfish (Tachysurus vachelli)
by Huaxing Zhou, Tong Li, Huan Wang, Ye Zhang, Yuting Hu, Amei Liu and Guoqing Duan
Toxins 2025, 17(6), 300; https://doi.org/10.3390/toxins17060300 - 12 Jun 2025
Viewed by 458
Abstract
Microcystin-leucine arginine (MC-LR) is a prominent water pollutant known for its potent hepatic toxicity. However, the effects of subchronic exposure to environmentally relevant concentrations of MC-LR on the fish liver remain poorly understood. This study aimed to systematically evaluate the impact of subchronic [...] Read more.
Microcystin-leucine arginine (MC-LR) is a prominent water pollutant known for its potent hepatic toxicity. However, the effects of subchronic exposure to environmentally relevant concentrations of MC-LR on the fish liver remain poorly understood. This study aimed to systematically evaluate the impact of subchronic MC-LR exposure on the liver of darkbarbel catfish (Tachysurus vachelli). A total of 270 one-year-old fish were exposed to MC-LR (0, 2, and 5 μg/L) for 28 days and sampled on days 14 (D14) and 28 (D28). Histopathological analysis revealed marked hepatic inflammation in the MC-LR treatment groups, manifested as cellular degeneration, hyperemia, and inflammation. MC-LR exposure induced oxidative stress, evidenced by elevated malondialdehyde (MDA) levels and compensatory upregulation of superoxide dismutase (SOD) activity on D28. While hepatic lipid profiles were not altered by low-dose MC-LR, significant elevation of low-density lipoprotein cholesterol (LDL-C) specifically on D28 indicated incipient lipid metabolic disorder. Metabolomic analysis demonstrated a higher sensitivity, highlighting the stress response of the liver to low-dose MC-LR exposure. The results suggest MC-LR exposure disrupted hepatic phosphatidylcholine (PC) biosynthesis and inhibited lipoprotein formation, thereby impairing lipid transport and contributing to lipid metabolic disorders. In summary, subchronic exposure to environmentally relevant concentrations of MC-LR-induced hepatic tissue inflammation, oxidative stress, and lipid metabolic disorders in darkbarbel catfish. Full article
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31 pages, 7685 KiB  
Article
Fish Health Enhancement and Intestinal Microbiota Benefits of Asian Seabass (Lates calcarifer Bloch, 1790) on Dietary Sea Lettuce (Ulva rigida C. Agardh, 1823) Extract Supplementation
by Nawanith Klongklaew, Sanikan Tansutaphanit, Pornphimon Tiewpair, Wararut Buncharoen, Jitraporn Phaksopa, Prapansak Srisapoome and Anurak Uchuwittayakul
Animals 2025, 15(12), 1714; https://doi.org/10.3390/ani15121714 - 10 Jun 2025
Cited by 1 | Viewed by 622
Abstract
This study investigates the health benefits of supplementing Asian seabass diets with hot water crude extract from the sea lettuce Ulva rigida (Ur-HWCE). The extract’s proximate composition consists of 57.63% carbohydrates, 6.75% protein, 31.96% ash, and 6.01% sulfate polysaccharides, as confirmed [...] Read more.
This study investigates the health benefits of supplementing Asian seabass diets with hot water crude extract from the sea lettuce Ulva rigida (Ur-HWCE). The extract’s proximate composition consists of 57.63% carbohydrates, 6.75% protein, 31.96% ash, and 6.01% sulfate polysaccharides, as confirmed by FTIR spectrum analysis. It also exhibits significant antioxidant properties, including total antioxidants, ABTS, DPPH, and reducing power. The study involved four groups fed Ur-HWCE at 0.5, 1.0, and 5 g/kg compared to a control group, with feed prepared daily and given twice at 5% of body weight for 4 weeks. Ur-HWCE supplementation did not negatively impact growth performance. It significantly upregulated insulin-like growth factor 1 (igf1) in the brain and liver, enhancing growth processes. Ur-HWCE reduced oxidative stress markers, such as malondialdehyde (MDA). Enhanced immune responses were observed, including increased bactericidal activity, serum IgM levels, and the upregulation of immune-related genes (dcs, c3, ighm, lyz, il8, il10). Gut microbiota analyses showed increased beneficial aerobic and natural probiotic Bacillus spp., particularly Bacillus amyloliquefaciens, enhancing gut health by reducing pathogenic bacteria. Blood biochemical parameters remained stable, and no histopathological alterations were found in the liver and intestine tissues, confirming the supplement’s safety. Fish fed with Ur-HWCE showed significantly higher survival rates and relative percent survival (RPS) against Vibrio vulnificus AAHM-VV2312 compared to the control group, demonstrating improved disease resistance. The study concludes that Ur-HWCE is a promising dietary supplement for enhancing the health, growth, and disease resistance of Asian seabass, supporting its potential in sustainable aquaculture practices. Full article
(This article belongs to the Special Issue Enhancing Aquatic Animal Health Through Feed Additives)
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23 pages, 19950 KiB  
Article
Genomic Characterization and Pathogenicity of a Novel Birnavirus Strain Isolated from Mandarin Fish (Siniperca chuatsi)
by Hetong Zhang, Dandan Zhou, Junjian Dong, Yunyun Yan, Shanshan Liu, Xing Ye, Jianguo He and Chengfei Sun
Genes 2025, 16(6), 629; https://doi.org/10.3390/genes16060629 - 24 May 2025
Viewed by 412
Abstract
Background: Birnaviruses infect a wide range of aquatic and terrestrial hosts, including several economically important fish species. This study aimed to isolate and characterize a novel birnavirus strain from mandarin fish (Siniperca chuatsi), a high-value freshwater species in Chinese aquaculture. Methods: [...] Read more.
Background: Birnaviruses infect a wide range of aquatic and terrestrial hosts, including several economically important fish species. This study aimed to isolate and characterize a novel birnavirus strain from mandarin fish (Siniperca chuatsi), a high-value freshwater species in Chinese aquaculture. Methods: A novel strain, designated mandarin fish birnavirus (MFBV), was isolated from diseased fish and propagated in SCK cells. The complete genome was determined using high-throughput sequencing and RACE. Viral replication kinetics, tissue distribution, and pathogenicity were assessed through in vitro infection, RT-qPCR, histopathology, and experimental challenges. In addition, disinfectant sensitivity and environmental stability were evaluated. Results: The MFBV genome comprises two segments (A: 3539 bp; B: 2719 bp), and phylogenetic analysis revealed close relatedness to largemouth bass birnavirus (LBBV) and Lates calcarifer birnavirus (LCBV). MFBV displayed rapid replication in SCK cells, completing a replication cycle in 8–10 h. In juvenile and fry fish, an experimental infection caused acute disease with cumulative mortality ranging from 41.8% to 83.6%, with fry showing higher susceptibility. Viral RNA was detected in multiple tissues (7.9 × 106–7.9 × 107 copies/μg RNA), and histopathological lesions were observed in the intestine, spleen, and kidney. MFBV was highly sensitive to glutaraldehyde (20 ppm), while other disinfectants showed reduced efficacy. Viral half-life ranged from 36.5 to 144.5 h at room temperature. Conclusions: These findings demonstrate that MFBV can induce acute systemic infection in mandarin fish. The results offer new insights into the genomic and biological features of birnaviruses, contributing to improved disease management and viral taxonomy. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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22 pages, 8985 KiB  
Article
Huanglian Jiedu Decoction Treats Ischemic Stroke by Regulating Pyroptosis: Insights from Multi-Omics and Drug–Target Relationship Analysis
by Yixiao Gu, Zijin Sun, Tao Li and Xia Ding
Pharmaceuticals 2025, 18(6), 775; https://doi.org/10.3390/ph18060775 - 23 May 2025
Viewed by 828
Abstract
Background: Ischemic stroke (IS) is a severe condition with limited therapeutic options. Pyroptosis, a type of programmed cell death linked to inflammation, is closely associated with IS-related damage. Studies suggest inflammation aligns with the traditional Chinese medicine (TCM) concept of “fire-heat syndrome”. Huanglian [...] Read more.
Background: Ischemic stroke (IS) is a severe condition with limited therapeutic options. Pyroptosis, a type of programmed cell death linked to inflammation, is closely associated with IS-related damage. Studies suggest inflammation aligns with the traditional Chinese medicine (TCM) concept of “fire-heat syndrome”. Huanglian Jiedu Decoction (HLJD), a TCM formula known for clearing heat and purging fire, has shown therapeutic effects on IS, potentially by regulating pyroptosis. Study design: Eight-week-old male mice were divided into six groups: sham operation, model, positive drug, and low-, medium-, and high-dose HLJD groups. After a week of adaptive feeding, mice received respective treatments for five days, followed by modeling on the sixth day, with samples collected 23 h post-perfusion. Analyses included multi-omics, physiology, histopathology, virtual drug screening, target affinity assessment, and molecular biology techniques to measure relevant indicators. Results: HLJD effectively mitigated IS-related damage, maintaining neurological function, reducing ischemic levels, protecting cellular morphology, inhibiting neuronal apoptosis, and preserving blood–brain barrier integrity. Bioinformatics of high-throughput omics data revealed significant activation of pyroptosis and related inflammatory pathways in IS. ScRNA-seq identified neutrophils, macrophages, and microglia as key pyroptotic cell types, suggesting potential therapeutic targets. Network pharmacology and molecular docking identified NLRP3 as a critical target, with 6819 ligand–receptor docking results. SPR molecular fishing, LC-MS, molecular dynamics, and affinity measurements identified small molecules with high affinity for NLRP3. Molecular biology techniques confirmed that HLJD regulates pyroptosis via the classical inflammasome signaling pathway and modulates the inflammatory microenvironment. Conclusions: Following IS, pyroptosis in myeloid cells triggers an inflammatory cascade, leading to neural damage. HLJD may inhibit NLRP3 activity, reducing pyroptosis and associated inflammation, and ultimately mitigating damage. Full article
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15 pages, 6490 KiB  
Article
Metabolomics-Based Analysis of Adaptive Mechanism of Eleutheronema tetradactylum to Low-Temperature Stress
by Minxuan Jin, Anna Zheng, Evodia Moses Mkulo, Linjuan Wang, Huijuan Zhang, Baogui Tang, Hui Zhou, Bei Wang, Jiansheng Huang and Zhongliang Wang
Animals 2025, 15(8), 1174; https://doi.org/10.3390/ani15081174 - 19 Apr 2025
Viewed by 445
Abstract
Temperature is a critical environmental factor that influences the growth, development, metabolism, and overall physiological performance of fish. Eleutheronema tetradactylum is an economically significant fish species; however, its molecular mechanism’s response to long-term cold stress is still unclear. In this study, we investigated [...] Read more.
Temperature is a critical environmental factor that influences the growth, development, metabolism, and overall physiological performance of fish. Eleutheronema tetradactylum is an economically significant fish species; however, its molecular mechanism’s response to long-term cold stress is still unclear. In this study, we investigated the physiological responses of the liver in E. tetradactylum exposed to a constant temperature of 18 °C for durations of both 7 and 14 days, utilizing liquid chromatography–mass spectrometry (LC-MS), metabolomics, and conventional biochemical assays. The antioxidant status, liver histology, and metabolite profiles were examined at different time points. Our results revealed that, following sustained cold exposure, the activities of key antioxidant enzymes—superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)—initially increased and then decreased. Additionally, levels of malondialdehyde (MDA), a marker of oxidative damage, significantly elevated after 7 and 14 days of cold stress. Histopathological examination of liver tissues showed varying degrees of vacuolation and nuclear atrophy in hepatocytes, indicating oxidative damage. Metabolomic profiling identified 87 and 116 differentially expressed metabolites in the liver on days 7 and 14, respectively. Pathway enrichment analysis revealed significant alterations in pathways related to carbohydrate digestion and absorption, glutathione metabolism, and glycerolipid metabolism. These findings suggest that mechanisms regulating cell membrane fluidity, energy metabolism, autophagy, and antioxidant defense are crucial for the adaptation of E. tetradactylum to cold stress. Overall, this study provides valuable insights into the molecular and physiological adaptations of E. tetradactylum to low temperature, highlighting the activation of protective antioxidant responses and modifications of metabolic pathways in the liver. Full article
(This article belongs to the Section Aquatic Animals)
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24 pages, 11117 KiB  
Article
Host–Microbiota–Parasite Interactions in Grass Carp: Insights from Ichthyophthirius multifiliis Infection
by Fangxiang Li, Dongdong Jiang, Qing Wang, Ouqin Chang, Jiyuan Yin, Meiling Yu and Houjun Pan
Microorganisms 2025, 13(4), 872; https://doi.org/10.3390/microorganisms13040872 - 10 Apr 2025
Cited by 1 | Viewed by 800
Abstract
The ciliate parasite Ichthyophthirius multifiliis poses significant threats to grass carp (Ctenopharyngodon idellus) aquaculture. However, the limited understanding of host microbiota shifts and immune responses hinders effective control strategies. This study integrated analyses of host pathological indices, immune response and skin/gill/gut [...] Read more.
The ciliate parasite Ichthyophthirius multifiliis poses significant threats to grass carp (Ctenopharyngodon idellus) aquaculture. However, the limited understanding of host microbiota shifts and immune responses hinders effective control strategies. This study integrated analyses of host pathological indices, immune response and skin/gill/gut microbiota shifts after I. multifiliis infection. A histopathological examination identified gill and fin tissues embedded with I. multifiliis, accompanied by epithelial necrosis, and inflammatory cell infiltration. Biochemical profiling revealed marked elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea (UREA), and creatinine (CREA) levels, indicating impaired hepatic and renal function. Quantitative RT-PCR analyses demonstrated the up-regulation of mucosal immune gene IgT and pro-inflammatory cytokine TNF-α while increasing the trend of systemic immune gene IgM. 16S rRNA sequencing revealed significant reductions in skin microbiota diversity. At the genus level, opportunistic pathogens Aeromonas and Vibrio proliferated in the intestine, whereas Flavobacterium and Candidatus Megaira increased in the skin and gills. Correlation analyses identified positive associations between Aeromonas/Vibrio abundance and host phenotype, contrasting with negative correlations observed for Sphingomonas, Acinetobacter, and Leifsonia. These findings demonstrate that I. multifiliis infection induces host microbiome dysbiosis and potentially opportunistic bacterial infections. This investigation advances our understanding of tripartite host–microbiota–parasite interactions and supports microbial community-based parasitosis control in fish culture. Full article
(This article belongs to the Special Issue Infectious Diseases in Aquaculture)
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12 pages, 6258 KiB  
Article
A Comparative Study Between Copy Number Alterations and PRAME Immunohistochemical Pilot Study in Challenging Melanocytic Lesions
by Jeana Chun, Ashley R. Scholl, Jennifer Crimmins, Michelle M. Schneider, M. Angelica Selim and Rami N. Al-Rohil
Cancers 2025, 17(7), 1218; https://doi.org/10.3390/cancers17071218 - 4 Apr 2025
Viewed by 464
Abstract
Introduction: Diagnostic uncertainty for ambiguous lesions that fall on the spectrum between nevi and melanoma remains a significant challenge and can have consequences for patient management. Methods: This study aimed to compare the diagnostic utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry [...] Read more.
Introduction: Diagnostic uncertainty for ambiguous lesions that fall on the spectrum between nevi and melanoma remains a significant challenge and can have consequences for patient management. Methods: This study aimed to compare the diagnostic utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry to molecular testing (FISH and SNP array) in 34 diagnostically challenging melanocytic lesions and 9 non-diagnostically challenging melanomas. Results: We conclude that while PRAME immunohistochemistry demonstrates high specificity (96.2%) in diagnostically challenging melanocytic lesions, its low sensitivity (12.5%) suggests that it should not replace histopathological evaluation in rendering the final diagnosis. Conclusions: These findings suggest that PRAME may serve as a useful adjunct in the diagnostic workup, particularly due to its high negative predictive value, but should be used in conjunction with other established diagnostic modalities. Full article
(This article belongs to the Special Issue Prediction of Melanoma)
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11 pages, 2735 KiB  
Article
Investigation of the Pathobiology of Edwardsiella piscicida—Septicemia in Largemouth Bass
by Grace Ramena, Suja Aarattuthodi, Gnanender Sriramoju and Yathish Ramena
Pathogens 2025, 14(4), 334; https://doi.org/10.3390/pathogens14040334 - 31 Mar 2025
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Abstract
Edwardsiella piscicida septicemia is a significant threat to aquaculture, causing substantial production and economic losses. The causative bacterium E. piscicida infects multiple fish species of aquaculture relevance. This study investigated the pathogenicity of catfish-derived E. piscicida in largemouth bass (Micropterus salmoides) [...] Read more.
Edwardsiella piscicida septicemia is a significant threat to aquaculture, causing substantial production and economic losses. The causative bacterium E. piscicida infects multiple fish species of aquaculture relevance. This study investigated the pathogenicity of catfish-derived E. piscicida in largemouth bass (Micropterus salmoides) fingerlings. The experimental infection of largemouth bass using genotypically distinct E. piscicida isolates resulted in significant fish mortality independent of the isolate genotypes. A specific correlation between discrete E. piscicida genotypes and fish mortalities was not identified. The histopathological assessment of tissues from infected fish revealed inflammatory lesions characteristic of bacterial septicemia. This study provides insights into the pathogenesis of heterologous E. piscicida isolates in largemouth bass fingerlings, which could be crucial in developing effective pathogen-targeted management strategies to combat a deadly disease. Full article
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