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11 pages, 682 KiB  
Article
Long-Term Outcomes of First-Line Anti-TNF Therapy for Chronic Inflammatory Pouch Conditions: A Multi-Centre Multi-National Study
by Itai Ghersin, Maya Fischman, Giacomo Calini, Eduard Koifman, Valerio Celentano, Jonathan P. Segal, Orestis Argyriou, Simon D. McLaughlin, Heather Johnson, Matteo Rottoli, Kapil Sahnan, Janindra Warusavitarne and Ailsa L. Hart
Biomedicines 2025, 13(8), 1870; https://doi.org/10.3390/biomedicines13081870 - 1 Aug 2025
Viewed by 109
Abstract
Background/Objectives: Anti-tumour necrosis factor (anti-TNF) medications were historically commonly prescribed as the first-line biologic treatment for chronic inflammatory pouch conditions. However, their use in these conditions is mainly based on retrospective studies of relatively small numbers of patients with short follow up periods. [...] Read more.
Background/Objectives: Anti-tumour necrosis factor (anti-TNF) medications were historically commonly prescribed as the first-line biologic treatment for chronic inflammatory pouch conditions. However, their use in these conditions is mainly based on retrospective studies of relatively small numbers of patients with short follow up periods. We aimed to describe the long-term outcomes of first-line anti-TNF therapy in a large, multi-centre, multi-national patient cohort with chronic inflammatory pouch conditions. Methods: This was an observational, retrospective, multi-centre, multi-national study. We included patients with chronic inflammatory pouch conditions initially treated with anti-TNF drugs infliximab (IFX) or adalimumab (ADA), who had a follow up of at least 1 year. The primary outcome was anti-TNF treatment persistence, defined as continuation of anti-TNF throughout the study period. The secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision. Results: We recruited 98 patients with chronic inflammatory pouch conditions initially treated with anti-TNF medications—63 (64.3%) treated with IFX and 35 (35.7%) treated with ADA. Average follow up length was 94.2 months (±54.5). At the end of the study period only 22/98 (22.4%) patients were still on anti-TNF treatment. In those in whom the first-line anti-TNF was discontinued, the median time to discontinuation was 12.2 months (range 5.1–26.9 months). The most common cause for anti-TNF discontinuation was lack of efficacy despite adequate serum drug levels and absence of anti-drug antibody formation (30 patients, 30.6%). Loss of response due to anti-drug antibody formation was the cause for discontinuation in 18 patients (18.4%), while 12 patients (12.2%) stopped treatment because of adverse events or safety concerns. Out of the 76 patients discontinuing anti-TNF treatment, 34 (34.7% of the cohort) developed pouch failure, and 42 (42.8% of the cohort) are currently treated with a different medical therapy. Conclusions: First-line anti-TNF therapy for chronic pouch inflammatory conditions is associated with low long-term persistence rates. This is due to a combination of lack of efficacy and adverse events. A significant percentage of patients initially treated with anti-TNF therapy develop pouch failure. Full article
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16 pages, 2701 KiB  
Article
The Lysine at Position 177 Is Essential to Limit the Inhibitory Capacities of Sprouty4 Protein in Normal and Cancer-Derived Cells
by Maximilian Schiwek, Kathrin Ruhdorfer, Christoph Pfurner and Hedwig Sutterlüty
Int. J. Mol. Sci. 2025, 26(15), 7353; https://doi.org/10.3390/ijms26157353 - 30 Jul 2025
Viewed by 190
Abstract
The Sprouty (Spry) proteins modulate signalling and regulate processes like cellular migration and proliferation. Here, we investigated a Spry4 alteration substituting a lysine at position 177 to an arginine, based on a mutation found in Kallmann syndrome, a genetically heterogeneous disease connected to [...] Read more.
The Sprouty (Spry) proteins modulate signalling and regulate processes like cellular migration and proliferation. Here, we investigated a Spry4 alteration substituting a lysine at position 177 to an arginine, based on a mutation found in Kallmann syndrome, a genetically heterogeneous disease connected to reduced fibroblast growth factor receptor1 (FGFR) signalling. Using growth curves to evaluate proliferative and scratch assays to determine migrative capacities of the cells, in normal fibroblasts as well as in osteosarcoma-derived cells, we demonstrate that the modified Spry4K177R version hinders both processes, which the unaltered protein cannot do under the same conditions. The inhibition of these processes was accompanied by lower relative phospho-extracellular-signal-regulated kinases (pERK) levels in response to serum induction, indicating that activation of MAPK was less efficient. In contrast to the situation in these cells of mesenchymal origin, in lung cancer-derived cell lines both variants of Spry4 were able to interfere with proliferation of tested cells, and in the cells with elevated FGFR1 expression the Spry4 proteins with an alteration at codon 177 were even more effective. In summary, these data indicate that the lysine at position 177 restricts the ability of Spry4 to inhibit signal transduction at least in cells with high FGFR1 levels. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sprouty Proteins in Cancer)
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21 pages, 2807 KiB  
Article
Phage Therapy Enhances Survival, Immune Response, and Metabolic Resilience in Pacific White Shrimp (Litopenaeus vannamei) Challenged with Vibrio parahaemolyticus
by Chao Zeng, Long Qi, Chao-Li Guan, Yu-Lin Chang, Yu-Yun He, Hong-Zheng Zhao, Chang Wang, Yi-Ran Zhao, Yi-Chen Dong and Guo-Fang Zhong
Fishes 2025, 10(8), 366; https://doi.org/10.3390/fishes10080366 - 30 Jul 2025
Viewed by 258
Abstract
Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at [...] Read more.
Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article
(This article belongs to the Special Issue Healthy Aquaculture and Disease Control)
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21 pages, 7017 KiB  
Article
Chronic Heat Stress Caused Lipid Metabolism Disorder and Tissue Injury in the Liver of Huso dauricus via Oxidative-Stress-Mediated Ferroptosis
by Yining Zhang, Yutao Li, Ruoyu Wang, Sihan Wang, Bo Sun, Dingchen Cao, Zhipeng Sun, Weihua Lv, Bo Ma and Ying Zhang
Antioxidants 2025, 14(8), 926; https://doi.org/10.3390/antiox14080926 - 29 Jul 2025
Viewed by 144
Abstract
High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts [...] Read more.
High-temperature stress has become an important factor that has restricted the aquaculture industry. Huso dauricus is a high-economic-value fish that has faced the threat of thermal stress. Based on this point, our investigation aimed to explore the detailed mechanism of the negative impacts of heat stress on the liver metabolism functions in Huso dauricus. In this study, we set one control group (19 °C) and four high-temperature treatment groups (22 °C, 25 °C, 28 °C, 31 °C) with 40 fish in each group for continuous 53-day heat exposure. Histological analysis, biochemical detection, and transcriptome technology were used to explore the effects of heat stress on the liver structure and functions of juvenile Huso dauricus. It suggested heat-stress-induced obvious liver injury and reactive oxygen species accumulation in Huso dauricus with a time/temperature-dependent manner. Serum total protein, transaminase, and alkaline phosphatase activities showed significant changes under heat stress (p < 0.05). In addition, 6433 differentially expressed genes (DEGs) were identified based on the RNA-seq project. Gene Ontology enrichment analysis showed that various DEGs could be mapped to the lipid-metabolism-related terms. KEGG enrichment and immunohistochemistry analysis showed that ferroptosis and FoxO signaling pathways were significantly enriched (p < 0.05). These results demonstrated that thermal stress induced oxidative stress damage in the liver of juvenile Huso dauricus, which triggered lipid metabolism disorder and hepatocyte ferroptosis to disrupt normal liver functions. In conclusion, chronic thermal stress can cause antioxidant capacity imbalance in the liver of Huso dauricus to mediate the ferroptosis process, which would finally disturb the lipid metabolism homeostasis. In further research, it will be necessary to verify the detailed cellular signaling pathways that are involved in the heat-stress-induced liver function disorder response based on the in vitro experiment, while the multi-organ crosswalk mode under the thermal stress status is also essential for understanding the comprehensive mechanism of heat-stress-mediated negative effects on fish species. Full article
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17 pages, 4113 KiB  
Article
Protective Effect of Camellia japonica Extract on 2,4-Dinitrochlorobenzene (DNCB)-Induced Atopic Dermatitis in an SKH-1 Mouse Model
by Chaodeng Mo, Md. Habibur Rahman, Thu Thao Pham, Cheol-Su Kim, Johny Bajgai and Kyu-Jae Lee
Int. J. Mol. Sci. 2025, 26(15), 7286; https://doi.org/10.3390/ijms26157286 - 28 Jul 2025
Viewed by 247
Abstract
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application [...] Read more.
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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27 pages, 1010 KiB  
Review
The Multifaceted Role of IL-35 in Periodontal Disease and Beyond: From Genetic Polymorphisms to Biomarker Potential
by Zdravka Pashova-Tasseva, Antoaneta Mlachkova, Kamen Kotsilkov and Hristina Maynalovska
Genes 2025, 16(8), 891; https://doi.org/10.3390/genes16080891 - 28 Jul 2025
Viewed by 305
Abstract
Periodontitis is a prevalent chronic inflammatory disease with complex etiopathogenesis involving microbial dysbiosis, host immune response, environmental factors, and genetic susceptibility. Among the cytokines implicated in periodontal immunoregulation, interleukin-35 (IL-35) has emerged as a novel anti-inflammatory mediator with potential diagnostic and therapeutic relevance. [...] Read more.
Periodontitis is a prevalent chronic inflammatory disease with complex etiopathogenesis involving microbial dysbiosis, host immune response, environmental factors, and genetic susceptibility. Among the cytokines implicated in periodontal immunoregulation, interleukin-35 (IL-35) has emerged as a novel anti-inflammatory mediator with potential diagnostic and therapeutic relevance. This narrative review evaluates the role of IL-35 in periodontal disease by exploring its local and systemic expression, response to non-surgical periodontal therapy (NSPT), and association with clinical disease severity. Additionally, current evidence regarding IL-35 gene polymorphisms and their potential contribution to individual susceptibility and disease progression, as well as their relevance in related systemic conditions, is assessed. A comprehensive review and synthesis of recent clinical and experimental studies were conducted, focusing on IL-35 levels in saliva, serum, and gingival crevicular fluid (GCF) among patients with healthy periodontium, gingivitis, and various stages of periodontitis, both before and after NSPT. Emphasis was placed on longitudinal studies evaluating IL-35 dynamics in correlation with periodontal parameters, as well as genetic association studies investigating IL-12A and EBI3 gene polymorphisms. IL-35 levels were generally found to be higher in healthy individuals and reduced in periodontitis patients, indicating a possible protective role in maintaining periodontal homeostasis. Following NSPT, IL-35 levels significantly increased, corresponding with clinical improvement and reduced inflammatory burden. Genetic studies revealed variable associations between IL-35 polymorphisms and susceptibility to periodontitis and related systemic conditions, although further research is needed for validation. IL-35 appears to function as a modulator of immune resolution in periodontal disease, with potential utility as a non-invasive biomarker for disease activity and therapeutic response. Its upregulation during periodontal healing supports its role in promoting tissue stabilization. The integration of cytokine profiling and genetic screening may enhance personalized risk assessment and targeted interventions in periodontal care. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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22 pages, 1822 KiB  
Article
Increased Concentration of Anti-Egg Albumin Antibodies in Cerebrospinal Fluid and Serum of Patients with Alzheimer’s Disease—Discussion on Human Serpins’ Similarity and Probable Involvement in the Disease Mechanism
by Dionysia Amanatidou, Magdalini Tsolaki, Vasileios Fouskas, Ioannis Gavriilidis, Maria Myriouni, Anna Anastasiou, Athanasia Papageorgiou, Diona Porfyriadou, Zoi Parcharidi, Eleftheria Papasavva, Maria Fili and Phaedra Eleftheriou
Biomolecules 2025, 15(8), 1085; https://doi.org/10.3390/biom15081085 - 27 Jul 2025
Viewed by 437
Abstract
Alzheimer’s Disease (AD) is a multifactorial process. Amyloid plaque formation constitutes the main characteristic of the disease. Despite the identification of numerous factors associated with AD, the mechanism remains unclear in several aspects. Disturbances in intestinal and blood–brain barrier (BBB) penetration, observed in [...] Read more.
Alzheimer’s Disease (AD) is a multifactorial process. Amyloid plaque formation constitutes the main characteristic of the disease. Despite the identification of numerous factors associated with AD, the mechanism remains unclear in several aspects. Disturbances in intestinal and blood–brain barrier (BBB) penetration, observed in AD, may facilitate immunologic response to food-derived antigens. In the present study, antibodies against egg albumin, bovine-casein, and N-Glycolyl-Neuraminic acid (Neu5Gc) were measured in the cerebrospinal fluid (CSF) and serum of the patients using an enzyme-linked immunosorbent assay (ELISA). Zero anti-Neu5Gc and low concentrations of anti-casein antibodies were detected. Increased anti-native egg albumin antibodies were present in the serum of patients of all stages with 65% positivity (p < 0.001) in mild disease and a higher percentage in females (81.9%, p < 0.001). Lower serum positivity to anti-denatured egg albumin antibodies was observed, showing a gradual increase with severity and higher prevalence also in females. In the CSF, anti-native and anti-denatured egg albumin antibodies were mainly observed in severely ill patients with accumulative positivity to either antigen, reaching 61.8% in severe vs. 15% in mild disease (p < 0.001). Increased values were mainly observed in males. Anti-egg albumin antibodies may be implicated in the disease mechanism through sequence/structural similarity with human proteins, mainly serpins, and it would be worth consideration in further investigations and therapeutic strategies. Full article
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14 pages, 659 KiB  
Article
Effects of Ursolic Acid on Immune Function and Antioxidative Capacity in Weaned Rabbits
by Yanhua Liu, Saijuan Chen, Fengyang Wu, Baojiang Chen, Chong Li, Xinyu Yang, Gang Zhang and Man Hu
Animals 2025, 15(15), 2159; https://doi.org/10.3390/ani15152159 - 22 Jul 2025
Viewed by 280
Abstract
This study aimed to investigate the effects of dietary supplementation with different levels of ursolic acid (UA) on the growth performance, immune function, intestinal antioxidant capacity, and anti-inflammatory responses of weaned rabbits. A total of 160 Hyla meat rabbits aged 35 days were [...] Read more.
This study aimed to investigate the effects of dietary supplementation with different levels of ursolic acid (UA) on the growth performance, immune function, intestinal antioxidant capacity, and anti-inflammatory responses of weaned rabbits. A total of 160 Hyla meat rabbits aged 35 days were randomly assigned to four groups. Each treatment group consisted of 8 replicates, with 5 rabbits per replicate. The rabbits were fed a basal diet (control group, CON) or experimental diets supplemented with 50, 100, or 200 mg/kg UA for 28 days. Dietary supplementation with 50 mg/kg UA significantly increased (p < 0.05) the average daily gain and average daily feed intake. The villus height, crypt depth, and villus height to crypt depth ratio exhibited quadratic responses (p < 0.05) to increasing dietary UA levels, with rabbits fed 50 mg/kg UA showing optimal ileal morphology. Compared with the CON group, dietary supplementation with 50 mg/kg UA significantly enhanced (p < 0.05) cecal catalase activity, secretory immunoglobulin A, and interleukin-10 (IL-10) levels, while the addition of 200 mg/kg UA increased (p < 0.05) serum catalase activity. The concentrations of serum tumor necrosis factor-α (TNF-α) and cecal IL-10 responded quadratically (p < 0.01 and p = 0.01, respectively) as the dietary UA level increased. With increasing UA supplementation, cecal Kelch-like ECH-associated protein 1 and IL-10 mRNA expression showed linear upregulation (p < 0.05), whereas nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1 (SOD1), quinone oxidoreductase 1 (NQO1), TNF-α, interleukin-6, and interleukin-8 displayed quadratic responses (p < 0.05). Dietary UA at 50 mg/kg significantly downregulated cecal TNF-α and interleukin-1β mRNA expression while upregulating Nrf2, NQO1, and SOD1 mRNA levels (p < 0.05). In conclusion, dietary supplementation with 50 mg/kg UA significantly improved the growth performance of weaned rabbits by improving intestinal morphology, immune function, and antioxidant and anti-inflammatory capacities, demonstrating its efficacy as a natural phytogenic feed additive. Full article
(This article belongs to the Special Issue Use of Agro-Industrial Co-Products in Animal Nutrition)
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14 pages, 2083 KiB  
Article
GDF-15 Levels in Gouty Arthritis and Correlations with Decreasing Renal Function: A Clinical Study
by Osman Cure, Ertugrul Yigit, Merve Huner Yigit and Hakki Uzun
Biomedicines 2025, 13(7), 1767; https://doi.org/10.3390/biomedicines13071767 - 18 Jul 2025
Viewed by 404
Abstract
Background/Objectives: Gouty arthritis (GA) is a chronic inflammatory disorder frequently linked to systemic inflammation and impaired kidney function. Growth differentiation factor-15 (GDF-15) has been suggested as a potential biomarker involved in both inflammatory responses and renal dysfunction. Studies on GDF-15 serum levels [...] Read more.
Background/Objectives: Gouty arthritis (GA) is a chronic inflammatory disorder frequently linked to systemic inflammation and impaired kidney function. Growth differentiation factor-15 (GDF-15) has been suggested as a potential biomarker involved in both inflammatory responses and renal dysfunction. Studies on GDF-15 serum levels and renal function decline in GA patients are limited. This study aimed to investigate serum GDF-15 levels in patients with GA and to evaluate the relationship between GDF-15 and renal function parameters. Methods: This prospective case–control study included 60 (intercritical group: 30; acute attack group: 30) patients with gout arthritis and 60 healthy controls, matched for body mass index and sex. The enzyme-linked immunosorbent assay measured serum GDF-15, and renal function and inflammatory markers were also assessed. Group comparisons used non-parametric tests, Spearman’s analysis evaluated correlations, and receiver operating characteristic (ROC) analysis assessed diagnostic performance. Results: Serum GDF-15 levels were significantly higher in GA patients than controls (p < 0.001), especially during acute attacks. GDF-15 correlated moderately with renal function markers. ROC analysis showed high diagnostic accuracy for both acute (area under the curve (AUC) = 0.98) and intercritical gout phases (AUC = 0.96). Conclusions: Serum GDF-15 levels are increased in patients with gouty arthritis and are associated with impaired renal function. GDF-15 may serve as a helpful biomarker for disease activity and renal involvement in GA, but its interpretation should be considered in conjunction with other clinical and laboratory parameters. Full article
(This article belongs to the Special Issue Emerging Trends in Kidney Disease)
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14 pages, 1031 KiB  
Article
Seroprevalence of IgG and IgE Antibodies Against Anisakis in the Presumably Healthy Population of the Canary Islands
by Eligia González-Rodríguez, Marta Rodero, J. Alberto Montoya-Alonso, Kevin M. Santana-Hernández, Myriam R. Ventura, Carmen Cuéllar and Eligia Rodríguez-Ponce
Antibodies 2025, 14(3), 60; https://doi.org/10.3390/antib14030060 - 17 Jul 2025
Viewed by 209
Abstract
Food-borne zoonoses, particularly anisakiosis caused by Anisakis spp., are an increasing public health concern due to the rising consumption of raw fish. Anisakiosis results from the ingestion of third-stage larvae of Anisakidae nematodes, with the genus Anisakis re-sponsible for approximately 97% of human [...] Read more.
Food-borne zoonoses, particularly anisakiosis caused by Anisakis spp., are an increasing public health concern due to the rising consumption of raw fish. Anisakiosis results from the ingestion of third-stage larvae of Anisakidae nematodes, with the genus Anisakis re-sponsible for approximately 97% of human cases. While regulatory protocols exist to minimize infection risk in commercial settings, domestic food preparation often lacks such safeguards, creating a gap in public health protection. In the Canary Islands, a major Spanish aquaculture region, farmed fish exhibit a low Anisakis prevalence, suggesting minimal risk from aquaculture products. In contrast, wild-caught fish demonstrate varia-ble parasitism, with recent studies reporting a 25% prevalence among commercial species. Methods: This study assessed Anisakis exposure in the Canary Islands by measuring specific IgG and IgE antibodies in 1043 serum samples collected from all seven islands between March 2014 and October 2015. ELISA assays detected anti-Anisakis antibodies, and the results were analyzed by age, sex, island, and isoclimatic zone. Results: Overall, 16.9% of samples were IgG-positive and 6.8% were IgE-positive. Seroprevalence was significantly higher in indi-viduals aged 60 years and above. Geographic heterogeneity was notable: La Palma had the highest IgG seroprevalence (35.3%), while El Hierro showed the highest IgE prevalence (16.3%). Temperate isoclimatic zones exhibited higher antibody prevalence than dry zones. These findings indicate variable Anisakis exposure across the Canary Islands, likely influenced by environmental and behavioral factors. Conclusions: The results highlight the need for targeted public health interventions to reduce the anisakiosis risk, particularly in regions and populations with elevated exposure. Full article
(This article belongs to the Section Antibody-Based Diagnostics)
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24 pages, 1481 KiB  
Article
Sources of Environmental Exposure to the Naturally Occurring Anabolic Steroid Ecdysterone in Horses
by Martin N. Sillence, Kathi Holt, Fang Ivy Li, Patricia A. Harris, Mitchell Coyle and Danielle M. Fitzgerald
Animals 2025, 15(14), 2120; https://doi.org/10.3390/ani15142120 - 17 Jul 2025
Viewed by 310
Abstract
Ecdysterone controls moulting and reproduction in insects, crustaceans, and helminths. It is also produced by many plants, probably as an insect deterrent. The steroid is not made by vertebrates but has anabolic effects in mammals and could be useful for treating sarcopenia in [...] Read more.
Ecdysterone controls moulting and reproduction in insects, crustaceans, and helminths. It is also produced by many plants, probably as an insect deterrent. The steroid is not made by vertebrates but has anabolic effects in mammals and could be useful for treating sarcopenia in aged horses. However, ecdysterone is banned in horseracing and equestrian sports, and with no limit of reporting, the risk of unintended exposure to this naturally occurring prohibited substance is a concern. To explore this risk, pasture plants and hay samples were analysed for ecdysterone content, as well as samples of blood, faeces, and intestinal mucosa from horses (euthanized for non-research purposes) with varying degrees of endo-parasite infestation. The variability in serum ecdysterone concentrations between different horses after administering a fixed dose was also examined. Ecdysterone was detected in 24 hay samples (0.09 to 3.74 µg/g) and several weeds, with particularly high concentrations in Chenopodium album (244 µg/g) and Solanum nigrum (233 µg/g). There was a positive correlation between faecal ecdysterone and faecal egg counts, but no effect of anthelmintic treatment and no relation to the number of encysted cyathostome larvae in the large intestine mucosa. Certain horses maintained an unusually high serum ecdysterone concentration over several weeks and/or displayed an abnormally large response to oral ecdysterone administration. Thus, the risk of environmental exposure to ecdysterone is apparent, and several factors must be considered when determining an appropriate dosage for clinical studies or setting a reporting threshold for equine sports. Full article
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19 pages, 1637 KiB  
Article
High-Tyrosol/Hydroxytyrosol Extra Virgin Olive Oil Enhances Antioxidant Activity in Elderly Post-Myocardial Infarction Patients
by Mojgan Morvaridzadeh, Mehdi Alami, Nada Zoubdane, Hawa Sidibé, Hicham Berrougui, Tamàs Fülöp, Michel Nguyen and Abdelouahed Khalil
Antioxidants 2025, 14(7), 867; https://doi.org/10.3390/antiox14070867 - 16 Jul 2025
Viewed by 409
Abstract
Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) [...] Read more.
Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) have shown promising antioxidant and anti-inflammatory effects, their specific roles in modulating oxidative stress biomarkers and high-density lipoprotein (HDL) functionality in elderly populations, especially in those with prior myocardial infarction, are not fully understood. This study aimed to investigate the effects of EVOO phenolic compounds on oxidative stress biomarkers and HDL functionality, and related metabolic outcomes in both healthy and post-myocardial infarction (post-MI) elderly individuals. This pilot randomized clinical trial study included healthy and post-MI participants aged 65–85 years. Participants in each group were randomly assigned to consume 25 mL per day of one of three types of olive oils: high phenolic (HTyr/Tyr) extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO) for a period of 26 weeks. Blood samples were collected at baseline and post-intervention to assess key biomarkers. Plasma levels of (poly)phenols, malondialdehyde (MDA), total antioxidant capacity (FRAP), lecithin-cholesterol acyltransferase activity (LCAT), and serum paraoxonase-1 (PON-1) activity were measured. A total of 34 individuals completed the study (mean age: 74 years). Baseline characteristics, including sex, age, body mass index (BMI), weight, blood pressure, and inflammatory markers like C-reactive protein (CRP) levels, did not differ significantly between the two groups. A significant increase in both FRAP levels and PON-1 activity was observed in post-MI participants following HP-EVOO consumption compared to baseline (p = 0.014). No significant changes were observed in MDA levels, LCAT activity, or plasma (poly)phenols. These results indicate that HP-EVOO may enhance antioxidant capacity, particularly FRAP and PON-1 activity, in elderly post-MI individuals. The observed differences between groups suggest that underlying cardiometabolic status may influence the response to olive oil phenolic compounds. Further studies are needed to explore the long-term cardiovascular effects. Full article
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22 pages, 2242 KiB  
Article
Quercetin Can Alleviate ETECK88-Induced Oxidative Stress in Weaned Piglets by Inhibiting Quorum-Sensing Signal Molecule Autoinducer-2 Production in the Cecum
by Hailiang Wang, Min Yao, Dan Wang, Mingyang Geng, Shanshan Nan, Xiangjian Peng, Yuyang Xue, Wenju Zhang and Cunxi Nie
Antioxidants 2025, 14(7), 852; https://doi.org/10.3390/antiox14070852 - 11 Jul 2025
Viewed by 429
Abstract
This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The [...] Read more.
This study evaluated the inhibitory activity of quercetin at sub-inhibitory concentrations on quorum-sensing (QS) molecules in vitro and the effects of dietary supplementation with quercetin (for 24 consecutive days) on enterotoxigenic Escherichia coli (ETEC)-induced inflammatory and oxidative stress responses in weaned piglets. The piglets were fed one of three diets: the basal diet (Con), ETEC challenge (K88) after the basal diet, or ETEC challenge (quercetin + K88) after the basal diet supplemented with 0.2% quercetin. In vitro experiments revealed that 5 mg/mL quercetin exhibited the strongest QS inhibitory activity and reduced pigment production by Chromobacterium violaceum ATCC12472 by 67.70%. In vivo experiments revealed that quercetin + K88 significantly increased immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) levels in the serum, ileum mucosa, and colon mucosa; increased glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) levels in the serum, liver, and colon mucosa; and decreased cluster of differentiation 3 (CD3) and cluster of differentiation 8 (CD8)activity in the serum compared with K88 alone. Quercetin + K88 significantly alleviated pathological damage to the liver and spleen and upregulated antioxidant genes (nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1(HO-1), CAT, SOD, and glutathione s-transferase (GST)). Inducible nitric oxide synthase (iNOS) and kelch-like ech-associated protein 1 (Keap1), which cause oxidative damage to the liver and spleen, were significantly downregulated. The acetic acid content in the cecum was significantly increased, and the E. coli count and QS signal molecule autoinducer-2 (AI-2) yield were significantly reduced. In conclusion, 0.2% dietary quercetin can alleviate ETEC-induced inflammation and oxidative stress in weaned piglets. Full article
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22 pages, 5061 KiB  
Article
Urolithin A Exhibits Antidepressant-like Effects by Modulating the AMPK/CREB/BDNF Pathway
by Yaqian Di, Rui Xue, Xia Li, Zijia Jin, Hanying Li, Lanrui Wu, Youzhi Zhang and Lei An
Nutrients 2025, 17(14), 2294; https://doi.org/10.3390/nu17142294 - 11 Jul 2025
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Abstract
Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and [...] Read more.
Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and explored the molecular mechanisms underlying these effects. Methods: We investigated the antidepressant effects and mechanisms of UA in a model of corticosterone-induced damage to PC12 cells and in a model of chronic socially frustrating stress. Results: Our results demonstrate that UA treatment (5 and 10 μM) significantly alleviated cellular damage and inflammation in corticosterone (CORT)-treated PC12 cells. Furthermore, UA administration (50 and 100 mg/kg) significantly reduced immobility time in the mouse tail suspension test (TST) and forced swim test (FST), indicating its antidepressant-like activity. Additionally, treatment with UA led to the activation of the cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling cascade and triggered the activation of adenosine monophosphate-activated protein kinase (AMPK) during these processes. Importantly, pretreatment with AMPK-specific inhibitor Compound C abolished UA’s cytoprotective effects in PC12 cells, as well as its behavioral efficacy in the FST and TST, and its neurotrophic effects, highlighting the critical role of AMPK activation in mediating these effects. Furthermore, in the chronic social defeat stress (CSDS) mouse model, UA treatment (50 and 100 mg/kg) significantly alleviated depression-like behaviors, including reduced sucrose preference in the sucrose preference test, increased social avoidance behavior in the social interaction test, and anxiety-like behaviors, including diminished exploration, in the elevated plus maze test, suggesting the antidepressant-like and anxiolytic-like activities of UA. Moreover, UA treatment reversed elevated serum stress hormone levels, hippocampal inflammation, and the decreased AMPK/CREB/BDNF signaling pathway in the hippocampus of CSDS mice. Conclusions: Together, these results provide compelling evidence for UA as a viable dietary supplement or therapeutic option for managing depression. Full article
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16 pages, 1599 KiB  
Article
Acute Immunological Biomarkers for Predicting Chronic Rheumatologic Disease After Chikungunya Virus Infection
by Anyela Lozano-Parra, Víctor Herrera, Luis Ángel Villar, Silvio Urcuqui-Inchima, Juan Felipe Valdés-López and Elsa Marina Rojas Garrido
Trop. Med. Infect. Dis. 2025, 10(7), 195; https://doi.org/10.3390/tropicalmed10070195 - 11 Jul 2025
Viewed by 440
Abstract
Early biomarkers are needed to predict the long-term persistence of rheumatical symptoms in patients infected with Chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to predict the risk of post-CHIK chronic rheumatism [...] Read more.
Early biomarkers are needed to predict the long-term persistence of rheumatical symptoms in patients infected with Chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to predict the risk of post-CHIK chronic rheumatism (pCHIK-CR) in adult patients of two prospective cohorts. We evaluated 46 febrile patients (median age: 33.5 years; IQR: 19 years; women: 50.0%) with CHIKV infection confirmed during the 2014–2015 outbreak in Santander, Colombia. The participants were classified by a rheumatologist as either cases (pCHIK-CR) or controls (WoRM, without rheumatical manifestations). We quantified serum levels of IL-4, IL-6, IL-8/CXCL-8, IL-27, CCL-2, CXCL-9, CXCL-10, and IgG using Luminex and ELISA assays during the acute and subacute phases of infection. Then, we evaluated the association of these immune factors with the case-control status using piecewise logistic regression adjusted for age and sex. There were non-linear associations between IL-8/CXCL-8, CXCL-9, and CXCL-10 with pCHIK-CR. Increases in the levels of IL-8/CXCL-8 (<35.7 pg/mL), CXCL-9 (≥6000 pg/mL), and CXCL-10 (≥36,800 pg/mL) were significantly associated with a reduced risk of pCHIK-CR (adjusted ORs: 0.85, 0.96, and 0.94, respectively). These results suggest that increases in IL-8/CXCL-8, CXCL-9, and CXCL-10 levels, measured in the early stages of CHIKV infection, may predict a chronic disease risk. This suggests the possibility that an early and strong immune response could contribute to enhancing CHIKV control and potentially reduce the risk of persistent joint symptoms. Given their expression patterns and timing, these three immune factors may be considered promising biomarker candidates for assessing the risk of chronic rheumatologic disease. These findings should be considered as exploratory and validated in additional cohort studies. Full article
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