Search Results (8,485)

Ozone (O₃) is a reactive oxidant increasingly applied in biomedical settings, yet its dose-dependent effects on innate immune cells, particularly those from non-human species, remain insufficiently defined. Within a One Health framework, this study examined how two clinically relevant O₃ exposure regimens (30 µg/mL and 90 µg/mL) affect porcine neutrophils and monocytes isolated from peripheral blood. Cell viability, reactive oxygen and nitrogen species (RONS) production, and the activity of key enzymes (myeloperoxidase, elastase, alkaline phosphatase, arginase) were assessed at 1 h and 24 h post-exposure. The lower dose induced mild functional activation without compromising viability, whereas the higher dose triggered pronounced oxidative stress, enhanced degranulation, and reduced neutrophil viability by more than 60%. Neutrophils exhibited a stronger and more dynamic response than monocytes, which retained viability and differentiation capacity at 30 µg/mL but showed impaired function at 90 µg/mL. These findings highlight the dual nature of O₃, where controlled exposure may support immunomodulation, while excessive dosing disrupts cell function. Defining safe and effective therapeutic windows remains critical for future applications. Full article

Sinensetin, a polymethoxylated flavone abundant in citrus fruits, has been recognized for its broad biological activities and wide use in traditional medicine around the world. Emerging clinical evidence from flavonoid-enriched orange juice interventions indicates antioxidant and anti-inflammatory effects, aligning with extensive preclinical data. In this review, we explored in vitro and in vivo findings on the anti-inflammatory and anticancer actions of sinensetin and delineated the underlying cellular pathways, especially in terms of proposed targets for sinensetin. In inflammatory settings, sinensetin attenuates NF-κB activation, lowers pro-inflammatory cytokines (e.g., TNF-α, IL-6), and enhances antioxidant defenses, supporting its reported antioxidant, anti-bacterial, anti-viral, and anti-obesity properties. Across multiple tumor models, sinensetin suppresses oncogenic signaling—including β-catenin, PI3K/AKT, VEGF, NRF2, P53, and MKK6—concomitant with reduced proliferation, migration, and survival signaling. We further discuss emerging immunological effects, including modulation of innate immune cell activation and cytokine production, which may contribute to tumor microenvironment reprogramming and inflammation resolution. Together, these mechanistic insights position sinensetin as a promising lead for chemopreventive and adjunct therapeutic strategies. Our efforts aim to provide insights into the future translational development and clinical evaluation of sinensetin and its derivatives. Full article

Autoinflammatory diseases involve recurrent systemic inflammation caused by dysregulated innate immunity, arising from genetic or multifactorial mechanisms, as seen in periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. About 10% of PFAPA patients show autosomal dominant inheritance. We describe a three-generation family with a PFAPA-like recurrent fever syndrome displaying clear autosomal dominant transmission. All affected individuals tested negative on a diagnostic panel of 13 known autoinflammatory genes. Whole-exome sequencing was performed in two distantly related affected members, followed by variant filtering, segregation analysis, and phenotype-based prioritization. A single heterozygous missense variant in RXFP1, c.154G>A p.(Asp52Asn), co-segregated with disease in all affected relatives. This variant is extremely rare in population databases, absent from ClinVar, present in COSMIC, and predicted as damaging by REVEL and CADD. RXFP1, not previously implicated in autoinflammatory or innate immune disorders, encodes the relaxin family peptide receptor 1, a G protein–coupled receptor involved in extracellular matrix regulation, anti-fibrotic pathways, and modulation of inflammatory cytokine production. Protein network analysis showed interactions with RLXN1-3, inflammatory mediators, PTGDR, ADORA2B, and C1QTNF8, supporting an immunomodulatory function. This is the first report linking RXFP1 variation to a hereditary recurrent fever syndrome, identifying relaxin signalling as a potential immune regulatory pathway. Full article

Background/Objectives: Antimicrobial peptides (AMPs), evolutionarily conserved components of innate immunity characterized by their broad-spectrum efficacy and minimal resistance development, are increasingly recognized as promising therapeutic candidates. This review aims to integrate current knowledge concerning natural and synthetic antimicrobial peptides and their therapeutic effectiveness in addressing gastrointestinal infections. Methods: A literature review was performed, evaluating recent peer-reviewed studies on AMPs. The research concentrated on their molecular mechanisms of action, antimicrobial spectrum, and their interactions with standard antibiotics. More in detail, the peptide classes examined herein included defensins, cathelicidins, histatins, and various natural peptides such as lactoferricin, protamines, RegIII, and hepcidin, along with synthetic analogs like WR12, D-IK8, MSI-78, and IMX942. Results: Natural AMPs demonstrated significant antimicrobial and immunomodulatory effects against Escherichia coli, Klebsiella pneumoniae, Salmonella spp., and Shigella spp. Beyond direct antimicrobial activity, antimicrobial peptides act as integrated anti-infective agents not only by modulating host–microbiota interactions, but also preserving epithelial barrier integrity, and limiting inflammation, thereby offering a multifaceted strategy to control gastrointestinal infections. On the other hand, synthetic peptides showed improved stability, reduced cytotoxicity, and synergistic interactions with antibiotics, which suggests that they could be used either alone or in combination with other treatments. Conclusions: AMPs constitute a promising category endowed with anti-infective activity, especially for therapy of intestinal diseases, which is attributed to their distinctive anti-infective mechanisms, immune-modulating characteristics, and a relatively low propensity for resistance development compared to conventional antibiotics. However, more clinical trials and improvements to their formulation are needed to translate promising in vitro results into reliable patient outcomes. Full article

Aquaculture has been established as a sustainable alternative to traditional fisheries, which face challenges such as overexploitation and environmental degradation. However, disease outbreaks, often caused by poor farming conditions, pollution, and environmental stress, remain a major concern, leading to economic losses and increasing the risk of antibiotic resistance due to the overuse of antibiotics. Therefore, it is crucial to seek new strategies that improve fish health and well-being, preventing drug resistance and promoting sustainable practices. GHRP-6, a synthetic growth hormone-releasing peptide that mimics ghrelin, has shown potential immunostimulatory properties and feed efficiency in fish. In this study, we evaluated the effects of orally administered GHRP-6 in an oil-based formulation on juvenile tilapia (Oreochromis sp.) challenged or unchallenged with Pseudomonas aeruginosa. We assessed its influence on immune gene expression and digestive enzyme activity. The results demonstrated that GHRP-6 treatment significantly enhanced growth performance (weight and length), reduced in vivo bacterial load after infection, and modulated key genes related to innate and adaptive immunity in the gills, intestine and head kidney. In addition, our results demonstrated, for the first time, a direct link between a growth hormone secretagogue in fish and the modulation of specific enzyme activity in the gut following a bacterial challenge. These findings highlight the potential of GHRP-6 as a dietary immunomodulator and growth promoter in fish farming, offering a promising strategy to reduce antibiotic usage and promote more sustainable aquaculture practices. Full article

Replication stress (RS) is a hallmark of cancer, largely driven by oncogene activation. Due to high levels of RS, cancer cells depend heavily on the RS response mechanisms to avoid DNA damage. This dependency creates a therapeutic opportunity that can be exploited for more effective cancer treatment. This review synthesizes current mechanistic understanding of RS and RS response and further describes how targeted disruption of RS response proteins (ATR, Chk1, Wee1, PARP, RPA) has been used in preclinical and clinical studies. We summarize preclinical and emerging clinical evidence for exploiting RS for radiosensitization, and outline candidate biomarkers and functional assays for patient selection. We also highlight the links between RS, therapy-induced senescence and innate immune activation via the cGAS–STING (cyclic GMP-AMP synthase—Stimulator of Interferon Genes) pathway, and address current challenges and future directions. Full article

Enteric infections remain a major health and economic challenge in swine production, with outcomes determined not only by pathogen virulence but also by the complex interplay between host genetics, immune competence, and the intestinal microbiota. This review synthesises current knowledge on host–pathogen genomic interactions in pigs, with a focus on resilience mechanisms against enteric diseases in swine. For this purpose, 103 articles were used as information sources, retrieved through structured keyword searches in PubMed. The review first addresses host genetic factors, highlighting genomic variants and quantitative trait loci associated with resistance or resilience to viral and bacterial pathogens such as porcine epidemic diarrhoea virus (PEDV) or Escherichia coli. Next, the key factors of the immune system to confer protection are also reviewed, emphasising the role of innate and adaptive responses in controlling each pathogen and disclosing the contribution of regulatory networks that balance pathogen clearance. Finally, the last section of the review is devoted to exploring current knowledge in the involvement of the microbiota in resilience against enteric pathogens, mostly, but not exclusively, enteric bacteria. In this sense, competitive exclusion is a concept which has gained attention in recent years. The review pinpoints and discusses the state of the art about how the microbial community provides colonisation resistance, shapes immune development, and influences pathogen fitness within the intestinal niche. As final perspectives, the review explores future drivers in the genetic immune and microbiota resistance. By bridging host genomic data with functional insights into immunity and microbial ecology, this review underscores the potential of multi-omics approaches to enhance resilience against enteric infections in pigs and advance sustainable swine health management. Full article

RhoA (Ras homolog A) is a prominent member of the Rho GTPase family, playing a key role in various cellular processes such as cytoskeletal dynamics, cell migration, and immune responses. However, its function in red swamp crayfish remains unclear. In this study, it is proposed that RhoA may regulate the innate immune response in P. clarkii. The gene was fully characterized as PcRhoA in P. clarkii. The results showed that the open reading frame (ORF) of PcRhoA is 663 bp, encoding a 220-amino acid protein with a conserved Rho domain of 174 amino acids. Phylogenetic analysis placed PcRhoA close to Cherax quadricarinatus RhoA. RT-qPCR analysis revealed high expression levels of the PcRhoA gene in the hepatopancreas, muscle, heart, ovary, and stomach, with lower expression in the blood, intestine, gills, and tentacle gland. Furthermore, PcRhoA mRNA transcript was significantly upregulated in the intestine following LPS and Poly I:C challenges. Knockdown of PcRhoA suppressed the expression of downstream genes in the immune signaling pathway. These results indicate that PcRhoA appears to play a pivotal role in regulating the immune response of crayfish. Full article

During exercise, increased oxygen consumption results in elevated production of reactive oxygen species (ROS). If the antioxidant system is unable to counteract this surge in ROS, oxidative stress occurs. Physical activity modulates both the generation and clearance of ROS through dynamic interactions between metabolic and antioxidant systems, and also influences the oxidative burst activity of phagocytes, a key component of the innate immune response. To investigate the acute physiological responses to high-intensity interval training (HIIT), we assessed the effects of a single HIIT session on oxidative stress markers and the oxidative burst activity of phagocytes in young professional athletes and non-athlete individuals. Blood samples were collected before and after a HIIT session from eleven male athletes (mean age: 22.1 ± 4.5 years) and ten male non-athlete university students (mean age: 21.6 ± 2.3 years). Participants performed a single treadmill HIIT session of ten 45-s intervals at 75–85% of heart rate reserve, separated by 45-s low-intensity recovery periods, with target intensities individualized using the Karvonen formula. Total antioxidant capacity, activities of catalase, superoxide dismutase and glutathione peroxidase enzymes, total serum nitrite/nitrate levels, lipid peroxidation products, and oxidative burst activity of phagocytes were evaluated before and after exercise. In athletes, a significant increase was observed in the activity of superoxide dismutase (from a median of 2.09 to 2.21 U/mL; p = 0.037) and catalase (from a median of 32.94 to 45.45 nmol/min/mL; p = 0.034) after exercise, whereas no significant changes were found in the control group. Total serum nitrite/nitrate levels significantly increased in both groups after exercise (athletes: from a median of 8.70 to 9.95 µM; p = 0.029; controls: from a median of 10.20 to 11.50 µM; p = 0.016). Oxidative burst capacity of peripheral blood phagocytes was significantly higher in athletes both before (median: 10,422 vs. 6766; p = 0.029) and after (median: 9365 vs. 7370; p = 0.047) the HIIT session compared to controls. Our findings demonstrate that training status markedly influences oxidative stress responses, with athletes exhibiting more effective long-term antioxidant adaptations. These results emphasize the necessity of tailoring exercise regimens to baseline fitness levels in order to optimize oxidative stress management across different populations. Full article

Vitamin D is a steroid hormone whose relevant immunomodulatory role has been widely described. Therefore, its contribution to the pathogenesis of immune-mediated diseases is an important and ongoing matter of research. Specifically, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with its receptor, exerts different activities on the innate and adaptive immune system, among which are suppression of inflammation and promotion of tolerogenic responses. Indeed, vitamin D insufficiency/deficiency has been related to the pathogenesis and/or disease activity of several autoimmune diseases, including, amongst others, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus. Based on these premises, in this review, we will describe the main molecular mechanisms modulated by vitamin D in the regulation of immune responses, including the induction of immune tolerance. Moreover, we will focus on the current knowledge regarding the contribution of vitamin D depletion to the aforementioned autoimmune diseases, seeking to provide evidence as to why its supplementation in the context of these immune-mediated disorders may potentially ameliorate disease activity and its related clinical manifestations. Full article

In this study, the synergistic effects of dietary Bacillus velezensis AAHM-BV2301, silica nanoparticles (SiNPs), and chitosan (CS) on the growth performance, innate immunity, gut microbiota, and disease resistance of Asian seabass (Lates calcarifer) fingerlings were evaluated. A total of 400 fish (11.25 ± 2.12 g) were assigned to five dietary treatments for 30 days: control, BV (1 × 10⁸ CFU/kg feed), BVSiNP (1 × 10⁸ CFU/kg + 2 mg SiNP/kg), BVCS (1 × 10⁸ CFU/kg + 15 g CS/kg), and BVSiNPCS (combined additives at the same concentrations). The growth indices (WG, SGR, RGR, and FCR) significantly increased in the fish fed BVSiNPs, whereas the level of innate immunity increased across all the supplemented groups, with BVCS and BVSiNPCS having the strongest respiratory burst and lysozyme activities. The tissue-specific modulation of immune-related genes (α2M, HSP70, Mx, and C3) was most pronounced in BVSiNP-fed fish, particularly in the gills and liver. Gut microbiome profiling revealed enrichment of Cetobacterium somerae in response to BV-based treatments, whereas BVSiNPCS induced the greatest increase in microbial richness and network connectivity. Postchallenge survival against Vibrio vulnificus was significantly greater in the BV and BVSiNP groups (p < 0.05). Overall, SiNPs acted as functional enhancers of the B. velezensis probiotic, supporting improved growth, immune activation, and microbiota restructuring. These results highlight the potential of nanoparticle-integrated synbiotics for microbiome-targeted health management in aquaculture. Full article

This review aims to systematically synthesize recent research advances on the antimicrobial peptides (AMPs) derived from the black soldier fly (Hermetia illucens). Against the backdrop of the escalating global crisis of antimicrobial resistance (AMR), AMPs have emerged as pivotal candidates to replace conventional antibiotics. As a unique saprophagous insect, H. illucens has evolved a robust and efficient innate immune system to thrive in its pathogen-rich environment. The AMPs it produces demonstrate remarkable broad-spectrum activity, high stability, and a low propensity for inducing resistance. Based on cutting-edge research available up to 2025, this article will provide an in-depth exploration of the astounding molecular diversity of H. illucens AMPs, their key structure–function relationships, and their multifaceted mechanisms of action, ranging from membrane disruption to immunomodulation. It will also highlight engineering strategies driven by artificial intelligence (AI). Finally, the review will assess the significant translational potential of these AMPs in combating multidrug-resistant bacteria, analyzing the current status of research in animal models, the challenges for industrial production, and viable future development pathways. The goal is to provide a solid theoretical foundation and forward-looking perspective to facilitate the translation of this valuable biological resource from basic research to clinical and agricultural applications. Full article

Patients with inflammatory bowel disease (IBD) frequently fail to achieve protective immunity after hepatitis B vaccination, even with intensified vaccination schedules. In this observational real-world study, 18 patients with IBD who were seronegative for hepatitis B virus (HBV) received three standard doses of the Engerix-B^® vaccine (at 0, 1, and 6 months). After immunisation, patients were classified into responders and non-responders according to their serological response. Blood samples were collected before the first dose and after completion of the vaccination schedule. Responders activated pathways that supported durable protection, including conventional dendritic cells type 1 mobilisation, expansion of IgG plasmablasts, and preservation of B- and T-cell memory. In contrast, non-responders displayed a more inflammatory innate profile, characterised by enrichment of CCR2⁺ monocytes. They also showed higher baseline Treg frequencies, which may suppress effective effector responses, together with impaired natural killer (NK) activation and progressive loss of memory potential. This study shows that hepatitis B vaccine failure in inflammatory bowel disease reflects a convergence of excessive immune regulation, inflammatory activation, and loss of memory potential, underscoring that no single pathway can explain the impaired response. Full article

Rapid weight loss (RWL) is a common strategy among combat sports athletes aiming for a competitive advantage. However, it imposes significant immunological stress that compromises both innate and adaptive immune defenses. This systematic review synthesizes current experimental and mechanistic evidence on the effects of RWL in combat sports, focusing on cellular immunity, neuroendocrine regulation, and inflammatory pathways. Acute RWL activates the hypothalamic–pituitary–adrenal axis, elevating plasma cortisol and suppressing lymphocyte proliferation, T-cell function, and natural killer cell cytotoxicity. Although neutrophil counts increase, their phagocytic and oxidative burst capacities decline, reflecting impaired host defense. Monocyte and macrophage systems shift toward proinflammatory phenotypes, while mucosal immunity is weakened by reductions in secretory immunoglobulin A, leading to increased upper respiratory tract infection risk. The magnitude and speed of weight loss are critical determinants of immune dysfunction, with reductions exceeding 5% of body mass producing particularly severe consequences. Evidence-based intervention strategies—including gradual weight management, nutritional optimization, and biomarker monitoring—are essential to mitigate immunosuppression and safeguard athlete health. This review highlights key gaps in combat sports-specific protocols and proposes integrated approaches to preserve immune competence and optimize performance. Full article

Immune dysregulation and chronic inflammation are central contributors to many diseases. Curcuma longa L. and Echinacea purpurea (L.) Moench are widely used medicinal plants with extensive preclinical evidence supporting immunomodulatory effects. Their key metabolites, curcuminoids, turmerones, alkamides, polysaccharides, and caffeic acid derivatives, engage with critical pathways, including NF-κB, MAPK, JAK/STAT, and Nrf2. This interaction modulates cytokine production, oxidative stress responses, and both innate and adaptive immune activities. Although numerous mechanistic and early clinical studies support these actions, human evidence remains inconsistent, partly due to poor and variable oral bioavailability and substantial heterogeneity in extract composition, despite the existence of some standardized preparations. Recent technological strategies, including micelles, phytosomes, phospholipid complexes, nanoemulsions, polymeric nanoparticles, and liposomal systems, have improved solubility, stability, and systemic exposure of key metabolites, particularly curcuminoids. However, clinical results are still limited and often derived from small or heterogeneous trials. This review summarizes the ethnopharmacological background, mechanistic data, clinical findings, and formulation advances for both species and highlights the translational barriers that restrict their therapeutic application. Rigorous clinical studies using standardized and technologically optimized preparations are required to determine the true immunomodulatory potential of C. longa and E. purpurea. Full article