Search Results (1,361)

The goal of this Special Issue was to collect the latest research results on the topics of (1) the physiological response of fish to various stressful situations and nutritional changes, (2) the replacement of fish meal and fish oil with sustainable, alternative protein and lipid sources in fish feeds, and (3) supplementing fish feeds with various additives in order to enhance the immune response and increase the stress and disease resistance of fish reared in intensive systems. These topics are very important for the development of a more effective and sustainable intensive aquaculture, as fish farming systems are becoming more intensive and industrialized, which results in a more stressful environment for farmed fish. Another important challenge is providing enough high-quality fish feed to fulfill the increasing demand of intensive aquaculture. There are 14 original research articles published in this Special Issue. The authors come from a wide array of countries, and they worked with a wide variety of freshwater and marine fish species, which are important for intensive aquaculture. These articles represent only a modest contribution to the overall literature of stress and nutritional physiology of farmed fish. However, each of these papers contain interesting new information regarding the solution of the two major problems of intensifying aquaculture: environmental stresses and nutrition management. Full article

This study highlights the strong ability of a new bacterial strain, Hafnia paralvei UUNT_MP29, isolated from the gastrointestinal tract (GIT) of common carp (Cyprinus carpio), to break down polystyrene (PS). As an omnivorous bottom feeder, C. carpio is constantly exposed to microplastics, creating a unique environment that favors the evolution of specialized microbiota capable of degrading polymers. Genomic analysis of the isolate identified key homologs involved in xenobiotic breakdown, including alcohol dehydrogenase (Adh), 3-hydroxybutyrate dehydrogenase (HDH), and a small glutamine-rich tetratricopeptide repeat-containing protein (SGTA), showing a strong metabolic system for processing long-chain hydrocarbons. Growth experiments showed the strain quickly adapted, reaching maximum cell density and forming mature biofilms by Day 16. Gravimetric analysis confirmed that H. paralvei UUNT_MP29 uses PS as its primary carbon source, with a significant weight loss of 16.76% over 16 days. Kinetic modeling indicated the degradation follows first-order kinetics (R² = 0.9243) with a high degradation rate constant (k) of 0.2078 day⁻¹. Surface analyses using FTIR and SEM confirmed extensive oxidative changes, as evidenced by the rising Carbonyl Index and surface erosion. TGA also showed reduced thermal stability of the treated polymer, suggesting microbial chain scission. These findings demonstrate the strong degradative ability of H. paralvei UUNT_MP29 and highlight the GIT of plastic-exposed aquatic animals as a promising area for discovering powerful biocatalysts for microplastic cleanup. Full article

Advances in mass spectrometry-based metabolomics have enabled the detection of numerous small molecules in biological systems, revealing complex metabolic alterations associated with cancer. Among these, dipeptides are consistently detected in plasma, serum, and tumor tissue metabolomic profiles, yet their biological significance is not fully understood. In most studies, circulating dipeptides are interpreted as nonspecific byproducts of protein degradation generated during increased proteolysis. However, accumulating evidence suggests that at least some endogenous dipeptides may have biological activities, including antioxidant effects, metabolic modulation, and potential signaling functions. In this review, we examine the possible origins, transport mechanisms, and biological implications of circulating dipeptides in cancer metabolomics. We discuss multiple sources of dipeptide generation, including intracellular proteolysis, autophagy, extracellular matrix remodeling, tumor cell death, host tissue catabolism, and microbiome metabolism. We also summarize current knowledge regarding peptide transport systems and intracellular dipeptide metabolism that may regulate the fate of these molecules within mammalian systems. In addition, evidence supporting the biological activities of certain endogenous dipeptides is reviewed to evaluate the possibility that some circulating dipeptides may function as bioactive metabolites. Finally, we propose conceptual frameworks for interpreting circulating dipeptides in cancer, including their potential roles as indicators of protein turnover, intermediates in amino acid recycling, stress-buffering molecules, metabolic signals, or components of tumor–host metabolic communication. A better understanding of circulating dipeptides may provide new insights into cancer metabolism and reveal previously overlooked metabolite classes with potential biomarker or functional significance. Full article

Belonging to the Euphorbiaceae family, the Jatropha genus is a promising source for the discovery of antitumor compounds. Jatropha ribifolia is a traditionally used species in folk medicine in the semi-arid region of Brazil, with a few chemical and pharmacological reports. Based on that, the aim of the current work is to isolate, structurally characterize, and assess the cytotoxic activity of isolated compounds through in vitro and in silico analyses. To achieve these main goals, the underground parts were dried, extracted and purified using classical and instrumental chromatographic techniques, leading to the isolation of 16 compounds. Altogether with HR-ESI-MS, IR, one- and two-dimensional NMR experiments, eight previously unreported diterpenes, named ribifolones A-H, along with eight known compounds, were obtained and are herein described. Regarding their activity against melanoma (SK-MEL-28) and colorectal cancer (HCT-116) cell lines, jatrophone was the most potent with IC₅₀ values of 6.19 µM and 10.09 µM, followed by ribifolone C that exhibited a moderate cytotoxicity with IC₅₀ values of 50.71 µM and 33.39 µM, respectively. Network pharmacology analysis suggests the involvement of the PI3K-AKT-mTOR pathway in the activity of both compounds; meanwhile, molecular docking and dynamics simulations demonstrate the main interactions with key proteins in the pathway, indicating putative targets. This work opens new perspectives for the discovery of bioactive compounds found in Euphorbiaceae species, especially from those occurring in Caatinga. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly recognized as key drivers of hepatocellular carcinoma (HCC). Unlike HCC caused by viral infections or alcohol, MASLD/MASH-related liver cancer develops within a chronic immunometabolic environment characterized by lipotoxicity, sterile inflammation, fibrogenesis, and remodeling of the microenvironment. In this setting, interleukin-10 (IL-10) has attracted growing attention due to its complex, context-dependent roles in immune regulation and tumor immune tolerance. This review explores IL-10 biology and its connection to MASLD/MASH-associated HCC, emphasizing the paradox that IL-10 may diminish harmful inflammation in early stages while promoting immunosuppressive conditions in advanced disease. To supplement existing research, we performed an exploratory reanalysis of publicly available bulk liver RNA-seq data from a mouse model that progresses from MASLD/MASH to HCC. The reanalysis revealed a receptor- and effector-specific rewiring of the IL-10 pathway: while the expression of canonical signaling genes (Stat3, Jak1, Jak2, Tyk2, Socs3) showed minimal changes across stages, receptor subunits (Il10ra, Il10rb) and IL-10-responsive effectors (such as Scd2, related to lipid metabolism, and Ddit4, involved in mTOR and glycolysis regulation) displayed strong stage-dependent induction. This was accompanied by a decrease in hepatocyte signature profiles and an increase in stromal and immune signatures. These results generate new hypotheses and raise key questions—particularly whether a large portion of IL-10 modulation originates from peripheral or non-parenchymal sources, and whether the transcriptional patterns observed reflect protein-level changes—that will require stage-specific, cell-focused human studies incorporating proteomic and cytokine measurements. Full article

As stem cell therapy in regenerative medicine becomes more socially accepted, human perinatal tissue is attracting attention as a source because it can be harvested non-invasively. Human placental extracts (HPEs), which are prepared using acid hydrolysis and autoclaving, have been approved for treating menopausal disorders and liver dysfunction. This study investigated a new HPE formulation prepared under milder conditions by omitting acid hydrolysis and autoclaving to improve its effectiveness. The new HPE contains relatively high-molecular-weight proteins, including high levels of thioredoxin-1, as well as primarily extracellular matrix proteins such as thrombospondin-1. These proteins appear to be intact or partially fragmented, but they can still potentially maintain their domain structure. The HPE showed both antioxidant and neurite outgrowth activities in a neuronal cell line SH-SY5Y. In a mouse model of hair graying caused by X-ray irradiation, multiple administration of the HPE significantly reduced it. Additionally, the HPE, but not heat-inactivated HPE, alleviated the mechanical allodynia in a mouse model with chemotherapy-induced peripheral neuropathy. Due to the fact that HPE can be produced non-invasively in large quantities in a short time without the need for culturing, the new HPE may have the potential to be an effective and feasible therapy via multiple mechanisms. Full article

Individuals with diabetes mellitus (DM) experience impaired wound healing, where the healing process is often compromised by a complex, hostile microenvironment characterized by persistent inflammation, high oxidative stress, and dysfunctional angiogenesis. The hyperglycemic environment damages the blood vessels and disturbs the normal hypoxia-induced upregulation of vascular endothelial growth factors, causes poor vascularization and insufficient production of new blood vessels, and leads to impaired perfusion and thickened and dysfunctional capillary basement membranes, which reduce blood flow to the wound, leading to delayed wound healing. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are the main effectors of intercellular communication and have emerged as a potent cell-free strategy for the acceleration of tissue repair. MSC-EVs can be isolated from various adult tissues, but increasing evidence suggests that placental MSC-derived EVs (PMSC-EVs) possess distinct clinical and biological advantages for enhancing diabetic wound healing. Placentas are unique cell sources for PMSCs, which can be easily acquired non-invasively from a discarded placenta and is ethically acceptable, and have superior proliferative capacity. The cargo of PMSC-derived EVs contains macromolecules such as proteins, mRNA, miRNA, and lipids, which may be tailored for fetomaternal tolerance and translates to unmatched immunomodulatory potential for resolving chronic diabetic inflammation. The PMSC-derived EVs also aid in enhancing multiple pathways, including modulation of inflammation, angiogenesis, and epithelial proliferation, that lead to increased wound healing. This article will highlight the unique advantages, specific mechanisms, and limitations of PMSC-derived EVs as an innovative non-cellular therapeutic modality in restoring vital repair processes and enhancing diabetic wound healing. Full article

Antimicrobial peptides (AMPs) are natural bioactive peptides produced by all organisms—from plants to insects, microbes and animals—and constitute a first line of defense. As they exhibit a broad spectrum of activity (antibacterial, antiviral, antifungal, antiparasitic, anticancer), strong efforts are being made to integrate AMPs into clinical use. AMPs are also being investigated as anticancer agents to overcome the side effects and/or resistance associated with current chemotherapies. In this context, we identified the natural AMP chionodracine from a new biological source: an Antarctic fish. Starting from the fragmentation of a chionodracine mutant peptide, a rational modular design approach was applied to develop three very short peptides (Pep-A, Pep-B and Pep-C), which were further modified with an N-terminal myristic acid lipid tail. The anticancer activity of the three N-myristoylated short peptides (Myr-A, Myr-B and Myr-C) was explored against the human cervical cancer HeLa cell line. The rationale behind this study is based on the previously reported antifungal activity of these myr peptides and on their ability to interact selectively with biological membrane-mimicking synthetic phospholipids without being particularly hemolytic or cytotoxic towards normal cells. We first demonstrated that myr peptides had cytotoxic activity against HeLa cells (IC₅₀ from 32 to 47 μM) but spared healthy primary human fibroblasts, whereas the corresponding non-myr peptides failed to kill cancer cells. The peptide with no hemolytic activity and a low IC₅₀, labeled Myr-B, was selected for subsequent analyses. Lactate dehydrogenase (LDH) assay and scanning electron microscopy (SEM) analysis revealed membrane damage and predominantly necrotic cell death in HeLa cells exposed to IC₅₀ doses of the Myr-B peptide, compared with cells treated with Pep-B. To thoroughly investigate the molecular effects of Myr-B in HeLa cells, we employed high-resolution label-free shotgun quantitative proteomics coupled with bioinformatics. Our results showed that exposing HeLa cells to Myr-B led to the under-expression of proteins belonging to the “apoptosis- and splicing-associated protein complex”, potentially influencing the alternative splicing process and consequently leading to a possible susceptibility to programmed cell death. These findings indicate that modifying natural AMPs may be a promising strategy for developing selective anticancer drugs and pinpoint Myr-B as an interesting target for future studies. Full article

Neutrophils are the most abundant circulating leukocytes and are characterized by a proteome in which granule-associated proteins synthesized during granulopoiesis constitute a major fraction of total cellular protein, reflecting their preloaded effector nature in innate immune defense. A striking feature of neutrophil biology is the unusual abundance of the calcium-binding proteins S100A8 and S100A9, which together form the heterodimeric complex known as calprotectin. Early biochemical studies estimated that S100A8/A9 constitutes a substantial fraction of the soluble cytosolic proteome in neutrophils, with later studies often describing it as one of the most abundant protein complexes in these cells. Despite extensive studies on the antimicrobial and inflammatory activities of calprotectin, the biological rationale for this unusual abundance remains incompletely understood. In this review, we examine the structural, biochemical, and regulatory features of S100A8/A9 and explore the potential explanations for its high abundance in the neutrophil cytosol. We first discuss the unique organization of the neutrophil proteome and the transcriptional programs governing granulopoiesis that lead to large-scale production of neutrophil effector proteins. We then review the structural and biochemical properties of S100A8/A9, including its calcium-dependent conformational dynamics and high-affinity transition metal binding, which contribute to antimicrobial defense through nutritional immunity. Several functional hypotheses are considered to explain calprotectin abundance, including roles as an antimicrobial reservoir, a metal-sequestering molecule, a regulator of oxidative stress, and a source of damage-associated molecular patterns. Finally, we discuss the evolutionary logic of neutrophil protein preloading and the implications of calprotectin biology in inflammatory diseases and the tumor microenvironment. Resolving the abundance paradox of S100A8/A9 may reveal fundamental principles governing the organization of innate immune cell proteomes and provide new insights into the strategies used by neutrophils to achieve rapid and effective host defense. Full article

In cold-region lakes, high organic matter concentrations with low bioavailability are common, yet the underlying causes and stabilisation mechanisms remain unclear. This study conducted a 60-day microbial treatment experiment in Hulun Lake using algae (DOMa), grass (DOMg), and manure (DOMm) as DOM sources. Fourier transform ion cyclotron resonance mass spectrometry and 16S rRNA analysis were employed to characterise DOM composition and bacterial communities. The bioavailability of DOMa, DOMg, and DOMm was 86.1%, 84.08%, and 70.9%, respectively. Differences in degradation cycles were mainly associated with the slowly biodegradable fraction; the half-lives of DOMa, DOMg, and DOMm were 49.51 days, 77.02 days, and 198.04 days, respectively. At the molecular level, proteins and lipids were rapidly utilised by microorganisms, leading to the generation of lignin, condensed aromatic hydrocarbons, and tannins, with many new molecules falling within the carboxylic acid-rich alicyclic molecule (CRAM) region. The overall community succession patterns of different DOM sources were highly similar, with initial DOM composition differences leading to variations in microbial communities during intermediate degradation stages (5~10 days). Moreover, microbiological processes facilitated the convergence of DOM source compositions and the accumulation of refractory organic matter. It is hypothesised that the regional climatic characteristics of the freeze–thaw cycle exacerbate organic matter accumulation by compressing the “effective degradation time”. These findings elucidate the causes of high organic matter and low bioavailability in cold-region lakes. Full article

The rapid global spread of antimicrobial resistance among pathogenic microorganisms poses a serious challenge to both human and animal health, underscoring the urgent need for new strategies to combat resistance. Antimicrobial peptides (AMPs), key components of the innate immune system, are promising candidates because they disrupt the membranes of bacteria, fungi, and viruses, thereby reducing the risk of resistance development. Lactoferrin (LF), a multifunctional iron-binding glycoprotein abundant in mammalian milk, is a rich source of AMPs. Cationic peptide fragments such as lactoferricin and lactoferrampin exhibit more potent direct antimicrobial activity than the intact protein. Our previous studies have shown that peptides derived from Equine milk lactoferrin exhibit antihypertensive, anti-inflammatory, and anti-oncogenic activity in silico, highlighting their multifunctional bioactive potential. Building on these results, the present study aims to investigate the antimicrobial properties of these peptides. We used an integrated approach combining computer modeling and in vitro studies to identify and validate novel antimicrobial peptides from equine milk lactoferrin. Bioinformatics tools, including AMPScanner and CAMP, were used to predict antimicrobial domains, followed by experimental testing against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The results showed that equine milk lactoferrin peptides possess potent and selective antimicrobial activity, with efficacy varying across bacterial species. These data expand the functional profile of lactoferrin-derived peptides, demonstrating their multifunctionality, and suggest that equine milk lactoferrin represents a promising natural source of antimicrobial agents, supporting alternative strategies to reduce antibiotic use in human and veterinary medicine. Full article

Functional pet food has grown rapidly, in line with the accelerated humanization of pets, growing attention to relations between diet and health, and mounting sustainability awareness. The article provides a critical overview of recent developments and new trends in functional pet food, combining data from published works, patents and market-driven innovative companies. The current trends depict a transition from single-nutrient fortification to integrated nutrition interventions through modulation of gastrointestinal health, immunity, metabolism, cognition and age-associated conditions. Special attention is dedicated to probiotics, prebiotics, postbiotics, polyphenols and novel protein sources, as well as innovations in processing and delivery technologies. The review highlights ongoing issues on the relevance of study design, available long-term safety information and our capacity to mechanistically underpin claims with respect to function. Because this review maps clusters of innovation and clusters of underdeveloped knowledge, it offers a roadmap for the translational pathway from scientific discovery to commercialization. The results highlight a call for harmonized methods, longer duration studies and integrative omics-based approaches in order to improve the evidence basis formulation and responsible marketing of future functional pet food products following credible, safe and sustainable strategies. Full article

Introduction: Periprosthetic joint infections (PJI) are among the most serious and costly complications in orthopedic surgery, significantly affecting patient prognosis and healthcare systems. Despite rigorous aseptic measures, intraoperative contamination of sterile fields, instruments, and air remains a persistent source of potential infection. This study investigates the relationship between the microbial contamination of sterile fields during arthroplasty and postoperative inflammatory markers, with the objective of determining whether the contamination of sterile fields correlates with the presence of periprosthetic joint infection (PJI). Material and Methods: This prospective observational study included 33 patients undergoing total hip or knee arthroplasty in a university-affiliated orthopedic center. Intraoperative samples were collected from sterile fields and equipment to detect microbial contamination, while postoperative monitoring involved the C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); leukocyte count; temperature; and wound assessment on days 1, 3 and 7. All patients received 48 h of prophylactic cefuroxime. Statistical analysis was conducted using the International Business Machines (IBM) Statistical Product and Service Solutions (SPSS) software for Windows, version 30.0 (IBM Corporation, Armonk, New York, United States of America) with significance set at p ≤ 0.05. Results: Postoperative inflammatory markers showed distinct patterns depending on the isolated microorganism, with Proteus vulgaris and Staphylococcus hominis ssp. consistently associated with higher CRP and leukocyte values, indicating a more intense systemic response. Staphylococcus epidermidis was the most frequently isolated species but showed moderate inflammatory profiles, suggesting its potential role in subclinical colonization. A strong correlation between CRP on day 3 and leukocyte count (r = 0.81) confirms their combined utility in the early detection of infectious complications, while ESR appeared less dynamic and more complementary in nature. Discussion: This study highlights the significant role of intraoperative contamination and microbial virulence in shaping the postoperative inflammatory response after arthroplasty. Elevated CRP and leukocyte levels, particularly on day 3, were closely associated with pathogens known for biofilm formation and chronic infections. Despite prophylactic antibiotic use, confirmed infections still occurred, suggesting the need to reassess current protocols and enhance intraoperative contamination control. Conclusions: Pathogen presence in sterile fields during arthroplasty increases the risk of periprosthetic joint infections, often without early clinical symptoms. CRP on day 3 and leukocyte count were the most reliable early indicators of persistent inflammation. Full article

Sterol Carrier Protein X (SCP-x) is an evolutionarily conserved lipid transport protein that plays important roles in sterol metabolism. In insects, cholesterol is an essential component of cellular membranes and the precursor of ecdysteroids, yet insects cannot synthesize cholesterol de novo and must obtain it from dietary sources. However, the functional role of SCP-x in cholesterol absorption and transport in insects remains poorly understood. In this study, the SCP-x gene from the migratory locust Locusta migratoria was identified and characterized using transcriptomic data from the midgut and fat body. The full-length LmSCP-x encodes a 404-amino-acid protein containing both the 3-oxoacyl-CoA thiolase domain and the sterol carrier protein-2 domain. Expression analysis revealed that LmSCP-x is predominantly expressed in the midgut and fat body, and subcellular localization experiments showed that the protein is mainly distributed in the cytoplasm. RNA interference-mediated knockdown of LmSCP-x significantly reduced cholesterol levels in the fat body and delayed nymphal development. Structural prediction using AlphaFold 3 further revealed a conserved three-dimensional structure of the SCP-2 domain, and molecular docking identified key amino acid residues involved in cholesterol binding, which were subsequently validated by bio-layer interferometry assays. Together, these results demonstrate that LmSCP-x plays a crucial role in cholesterol transport in L. migratoria and provide new insights into sterol metabolism in insects, offering potential targets for the development of novel pest management strategies. Full article

Introduction: Clostridioides difficile (C. difficile) is a major cause of antibiotic-associated diarrhea and healthcare-associated infections, with rising global incidence and severity due to the emergence of hypervirulent strains. Methods: This review synthesizes recent literature on the epidemiology, pathogenesis, diagnostic approaches, and therapeutic strategies related to C. difficile infection (CDI). Sources were selected from peer-reviewed journals, clinical guidelines, and emerging research between 2020 and 2025. Results: Advances in molecular diagnostics have improved the accuracy and speed of CDI detection. New therapeutic options such as fidaxomicin offer narrower-spectrum antibiotic activity with reduced recurrence rates. Fecal microbiota transplantation (FMT) has emerged as a highly effective option for recurrent CDI. Preventive efforts, including antibiotic stewardship programs and early-phase vaccine trials, show potential in reducing infection rates. Discussion: The management of CDI is evolving rapidly with the integration of precision diagnostics, targeted therapies, and microbiome-based interventions. Preventive strategies are critical, particularly in healthcare settings where C. difficile persists in the environment. Continued research and coordinated public health efforts are essential to reduce disease burden, improve outcomes, and limit transmission. Conclusions: Clostridioides difficile infections remain a major healthcare challenge with rising incidence and recurrent cases. Fidaxomicin has become the preferred first-line therapy. Microbiota-based therapies (like FMT, Rebyota, and Vowst) and Lipopolysaccharide Binding Protein (LBP) are highly effective for recurrent CDI prevention. Diagnostic strategies have improved with multi-step testing, enhancing accuracy and reducing overtreatment. Future focus lies in vaccines, targeted antimicrobials, and stricter prevention through antibiotic stewardship and hygiene. Full article