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Search Results (164)

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Keywords = antimicrobial and immunomodulatory proteins

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31 pages, 5980 KB  
Article
SIOOT® Adjunct Oxygen-Ozone Therapy Against Multidrug-Resistant Bacteria: A Pilot Study of 257 Cases
by Marianno Franzini, Salvatore Chirumbolo, Giovanni Ricevuti and Luigi Valdenassi
Antibiotics 2026, 15(8), 768; https://doi.org/10.3390/antibiotics15080768 - 10 Aug 2026
Abstract
Background/Objectives: Antimicrobial resistance (AMR) represents one of the greatest challenges to modern medicine, particularly in chronic infections sustained by multidrug-resistant (MDR) pathogens and biofilm formation. SIOOT® Oxygen–ozone major autohemotherapy (SIOOT®-O2-O3-MAHT) has been proposed as an adjunctive [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) represents one of the greatest challenges to modern medicine, particularly in chronic infections sustained by multidrug-resistant (MDR) pathogens and biofilm formation. SIOOT® Oxygen–ozone major autohemotherapy (SIOOT®-O2-O3-MAHT) has been proposed as an adjunctive treatment capable of exerting direct antimicrobial, antibiofilm, and immunomodulatory effects. This pilot study evaluated the clinical, microbiological, inflammatory, and mechanistic effects of standardized SIOOT®-O2-O3-MAHT administered alongside conventional antibiotic therapy in patients with chronic MDR bacterial infections. Methods: A prospective longitudinal pilot study was conducted in 257 patients with chronic infectious and inflammatory disorders refractory to prolonged antibiotic treatment. Patients received standardized SIOOT®-O2-O3-MAHT according to protocols from the Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT) in addition to guideline-directed antibiotics. Longitudinal bacterial burden (CFU/mL), culture positivity, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were all assessed over a 12-month follow-up. In parallel, macrophage phagocytosis, intracellular bacterial killing, phago-lysosomal maturation, and methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption were investigated using confocal laser scanning microscopy, gentamicin protection assays, and scanning electron microscopy. Results: SIOOT®-O2-O3-MAHT was associated with a progressive reduction in bacterial burden from a geometric mean of 6.43 × 106 CFU/mL before treatment to complete microbiological clearance after one year. Mean bacterial reduction reached 98.53% after one week and 99.95% after one month, while culture positivity decreased from 100% to 0% by one year (all p < 0.0001). ESR normalization increased from 28.2% at one week to 98.1% at one year, and CRP normalization increased from 32.4% to 98.7%. Mechanistic analyses demonstrated significantly enhanced macrophage phagocytosis, phago-lysosomal maturation, intracellular MRSA killing, and marked disruption of mature MRSA biofilms following ozone treatment. Conclusions: Adjunctive SIOOT®-O2-O3-MAHT was associated with reductions in bacterial burden, progressive improvement of systemic inflammatory markers, enhanced macrophage antimicrobial activity, and disruption of bacterial biofilms in patients with chronic multidrug-resistant infections. Given the prospective, non-randomized pilot design, these findings should be considered exploratory and hypothesis-generating, providing biological and clinical rationale for further investigation. Adequately powered randomized controlled trials are required to determine the efficacy, safety, and long-term clinical benefits of adjunctive oxygen–ozone therapy. Full article
(This article belongs to the Special Issue Advances in Antimicrobial Action and Resistance)
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27 pages, 2111 KB  
Review
Sustainable Protein Transitions: A Comprehensive Review of Insect Meal in Broiler Diets—Nutritional Value, Immunomodulatory Effects, Gut Health Interactions, and Future Perspectives
by Osama K. Abou-Emera
Biology 2026, 15(15), 1320; https://doi.org/10.3390/biology15151320 - 6 Aug 2026
Viewed by 166
Abstract
Broiler production keeps intensifying, and the environmental cost of the protein sources that feed it, principally soybean meal and fishmeal, has become harder to justify. Insect meal, derived chiefly from black soldier fly larvae (Hermetia illucens), yellow mealworm (Tenebrio molitor [...] Read more.
Broiler production keeps intensifying, and the environmental cost of the protein sources that feed it, principally soybean meal and fishmeal, has become harder to justify. Insect meal, derived chiefly from black soldier fly larvae (Hermetia illucens), yellow mealworm (Tenebrio molitor), and housefly larvae (Musca domestica), has emerged as a candidate able to address nutritional, immunological, and ecological goals at once. This review evaluates the evidence on the nutritional composition, digestibility, growth performance, immunomodulatory mechanisms, and gut health effects of insect meal in broiler diets, and weighs these findings against sustainability and economic considerations. The amino acid profile of insect meal is favorable, the fatty acid composition is distinctive, and bioactive compounds, chitin, antimicrobial peptides, and lauric acid among them, shape both innate and adaptive immune responses, reshape the gut microbiota, and reinforce mucosal integrity. Growth performance at partial replacement levels of soybean meal or fishmeal (5–15%) is broadly encouraging, although results differ across insect species, inclusion rate, and processing method. The immunomodulatory pathways involved, Toll-like receptor signaling, cytokine regulation, macrophage polarization, and immunoglobulin synthesis, converge on chitin acting simultaneously as a prebiotic substrate and an immune adjuvant. Critical knowledge gaps persist, including substantial variability in biological outcomes across insect species and rearing substrates, the absence of standardized processing protocols, limited mechanistic data from avian in vivo challenge models, and insufficient long-term validation under commercial production conditions. Cost and regulatory fragmentation across jurisdictions still constrain commercial uptake. Realizing the full potential of insect meal in sustainable broiler production will depend on multi-omics research, precision nutrition tools, and rigorous life-cycle assessment. Full article
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18 pages, 24230 KB  
Article
SMAD4–BPIFA1 Axis Governs Airway Antiviral Defense in Myhre Syndrome
by Yuanpu P. Di, Bodong Wen, Fengyuan Li, Felicia Tang, Dena Shen, Mark E. Lindsay, Angela E. Lin, Yin Chen and Hongmei Mou
Biomolecules 2026, 16(8), 1118; https://doi.org/10.3390/biom16081118 - 31 Jul 2026
Viewed by 272
Abstract
Myhre syndrome is a rare autosomal-dominant disorder caused by gain-of-function (GOF) variants in SMAD4. Although it is primarily recognized as a fibrotic disease, we and others have identified respiratory infection-associated morbidity as a major clinical burden. Regardless, the epithelial-intrinsic mechanisms underlying increased viral [...] Read more.
Myhre syndrome is a rare autosomal-dominant disorder caused by gain-of-function (GOF) variants in SMAD4. Although it is primarily recognized as a fibrotic disease, we and others have identified respiratory infection-associated morbidity as a major clinical burden. Regardless, the epithelial-intrinsic mechanisms underlying increased viral susceptibility in Myhre syndrome remain poorly understood. Here, using patient-derived nasal airway epithelial cells (NECs) and respiratory syncytial virus (RSV) infection as a model, we demonstrate that infection is markedly exacerbated in Myhre syndrome epithelium relative to matched healthy controls. We further show that activation of TGF-β1–SMAD4 signaling in healthy donor NECs phenocopies augmented RSV susceptibility, identifying SMAD4 signaling as a bona fide pro-viral pathway in airway epithelium. Mechanistically, we identify a significant reduction in BPIFA1 expression in Myhre syndrome NECs. BPIFA1 is a key secreted innate defense protein with antimicrobial, immunomodulatory, and emerging antiviral functions. SMAD signaling suppresses BPIFA1 expression, and its knockdown in healthy cells mimics the increased viral susceptibility, linking SMAD4 gain-of-function to impaired epithelial immunity. Therapeutically, we evaluated novel, stabilized 24-amino acid BPIFA1-derived peptides as a potential intervention. Treatment with active peptides (A4-153 and A4-X7) significantly reduced RSV infectivity and epithelial damage in both healthy and Myhre syndrome airway epithelial cultures, whereas a scrambled control peptide (A4-198) showed no significant effect. Collectively, our findings establish that GOF SMAD4 signaling enhances viral vulnerability in airway epithelium through suppression of BPIFA1-mediated antiviral defense and demonstrate that BPIFA1-derived peptide therapeutics represent a promising strategy to restore innate antiviral protection. Full article
(This article belongs to the Special Issue Lung Diseases: From Molecular Mechanisms to Therapeutics)
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17 pages, 2354 KB  
Article
KI17: A Bioinspired Peptide Derived from Talisia esculenta with In Vitro Anticancer and Immunomodulatory Activities
by Ana Paula Ramos Pereira, Ana Cristina Jacobowski, Camila de Oliveira Gutierrez, Octávio Luiz Franco, Marlon Henrique Cardoso, Thaís de Andrade Farias Rodrigues, Rodrigo Juliano Oliveira, Priscila Aiko Hiane, Rita de Cássia Avellaneda Guimarães, Ana Paula de Araújo Boleti and Maria Lígia Rodrigues Macedo
Molecules 2026, 31(14), 2434; https://doi.org/10.3390/molecules31142434 - 11 Jul 2026
Viewed by 428
Abstract
Cancer therapy remains limited by drug resistance and poor selectivity, while inflammation-driven tumor progression further complicates treatment outcomes. Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives due to their multifunctional properties. In this study, we investigated the anticancer and immunomodulatory activities of [...] Read more.
Cancer therapy remains limited by drug resistance and poor selectivity, while inflammation-driven tumor progression further complicates treatment outcomes. Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives due to their multifunctional properties. In this study, we investigated the anticancer and immunomodulatory activities of KI17, a rationally designed peptide derived from GL18, a peptide fragment identified from the talisin protein of Talisia esculenta. KI17 exhibited dose-dependent antiproliferative effects against murine and human melanoma (B16F10-Nex2, SK-MEL-2, A375) and cervical cancer (HeLa) cell lines, while displaying reduced cytotoxicity toward non-tumoral BV-2 microglial cells, resulting in a favorable selectivity index. Mechanistic analyses revealed that KI17 induces morphological alterations, mitochondrial dysfunction, caspase activation, and late-stage apoptosis, together with G0/G1 cell cycle arrest accompanied by accumulation of the Sub-G0 population, indicating coordinated regulation of cell death and cell cycle progression. KI17 effectively suppressed lipopolysaccharide (LPS)-induced microglial activation, markedly reducing pro-inflammatory cytokine and nitric oxide production without compromising cell viability. These biological activities are consistent with the peptide’s optimized physicochemical features, including increased cationicity, amphipathicity, and α-helical folding. Overall, our findings demonstrate that KI17 combines selective anticancer activity with potent immunomodulatory effects, highlighting its potential as a bioinspired peptide for further preclinical development in cancer therapy. Full article
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32 pages, 17781 KB  
Review
Biological and Immunological Activities of Brazilian Wasp Venoms: Implications for Allergy and Ion-Channel Modulation
by Jacqueline Ramos Machado Braga
Allergies 2026, 6(3), 26; https://doi.org/10.3390/allergies6030026 - 8 Jul 2026
Viewed by 754
Abstract
Background: Brazilian wasp venoms represent a clinically relevant yet underexplored source of bioactive molecules with important implications for allergy, toxicology, and neuropharmacology. This review discusses the biological and immunological activities of venoms from Neotropical wasp species prevalent in Brazil, particularly within the genera [...] Read more.
Background: Brazilian wasp venoms represent a clinically relevant yet underexplored source of bioactive molecules with important implications for allergy, toxicology, and neuropharmacology. This review discusses the biological and immunological activities of venoms from Neotropical wasp species prevalent in Brazil, particularly within the genera Polybia, Synoeca, Polistes, and Agelaia, with emphasis on venom composition, IgE-mediated hypersensitivity, and ion-channel modulation. Methods: A narrative literature review was conducted using studies focused on venom characterization, electrophysiological effects, immune responses, and clinical manifestations associated with Brazilian and other Hymenoptera species. Results: Brazilian wasp venoms contain a diverse repertoire of peptides, enzymes, and low-molecular-weight compounds that act synergistically on multiple cellular targets. Among these, mastoparan-like peptides exhibit antimicrobial, immunomodulatory, and membrane-disruptive activities, contributing to inflammation and cellular dysfunction. In addition, several venom components interact with ion channels and neuronal receptors, modulating neuronal excitability and synaptic signaling, which highlights their potential applications in neuropharmacology. Simultaneously, allergenic proteins can induce IgE sensitization and immediate hypersensitivity reactions ranging from localized manifestations to systemic anaphylaxis. The marked taxonomic and biochemical diversity of Brazilian wasps contributes to substantial variability in venom composition and clinical outcomes. Conclusions: Overall, these venoms constitute a valuable and still insufficiently explored source of biologically active compounds with potential applications in allergy diagnosis, venom immunotherapy, and drug development. Full article
(This article belongs to the Section Physiopathology)
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28 pages, 942 KB  
Review
Immunomodulatory Empty/Hollow Nanoparticles as Potential Therapeutic Strategies for Septic Shock
by Gracy Xavier Rosario, Gelilla Daniel, Philemon Shallie, Danielle Kinsey, Nathan Carpenter, Othman Sheikh Hussein and Cuthbert Ormond Simpkins
Biomedicines 2026, 14(7), 1460; https://doi.org/10.3390/biomedicines14071460 - 27 Jun 2026
Viewed by 349
Abstract
Septic shock is a life-threatening manifestation of sepsis characterized by dysregulated immune responses, excessive inflammation, oxidative stress, and progressive multi-organ dysfunction. Despite advances in antimicrobial therapy and supportive care, mortality remains high, highlighting the need for therapeutic strategies that target immune dysregulation in [...] Read more.
Septic shock is a life-threatening manifestation of sepsis characterized by dysregulated immune responses, excessive inflammation, oxidative stress, and progressive multi-organ dysfunction. Despite advances in antimicrobial therapy and supportive care, mortality remains high, highlighting the need for therapeutic strategies that target immune dysregulation in addition to infection control. The review evaluates the potential of hollow nanoparticles as immunomodulatory therapies for septic shock, focusing on lipid-based, polymeric, protein-based, biomimetic, inorganic, carbon-based, and hybrid nanoparticle platforms. Current evidence suggests that these systems can modulate key pathological processes through reactive oxygen and nitrogen species (RONS) scavenging, regulation of inflammatory signaling, macrophage modulation, neutralization of bacterial toxins and antigens, and, in some cases, direct antimicrobial activity. Among the available platforms, lipid-based and biomimetic nanoparticles appear to possess the greatest translational potential owing to their favorable immunomodulatory properties and improved biocompatibility. Nonetheless, several challenges continue to limit clinical translation, including nanoparticle-associated systemic and organ toxicity, unintended immunogenicity, limited long-term safety data, and the lack of standardized comparative studies across nanoparticle classes. Despite these limitations, the progression of VBI-S, a phospholipid nanoparticle formulation, to Phase III clinical evaluation highlights the growing clinical feasibility of such nanoparticle-based approaches for septic shock. Future research should focus on optimizing nanoparticle design, improving safety profiles, and establishing standardized preclinical and clinical evaluation frameworks. Collectively, the available evidence suggests that hollow nanoparticles represent a promising antibiotic-independent strategy for restoring immune homeostasis and improving outcomes in septic shock. Full article
(This article belongs to the Section Nanomedicine and Nanobiology)
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22 pages, 3665 KB  
Review
Transforming Beach-Accumulated Seaweed into High-Value Bioactive Products: A Recycling Perspective
by Dinusha Shiromala Dissanayake, Thilina U. Jayawardena and Dineth P. Nagahawatta
Recycling 2026, 11(7), 116; https://doi.org/10.3390/recycling11070116 - 26 Jun 2026
Viewed by 891
Abstract
Due to large-scale macroalgal blooms, nutrient enrichment, and changes in ocean circulation brought on by climate change, beach-accumulated seaweed (BAS) has quickly become a global environmental and waste-governance concern. Despite degradation and contamination during beach stranding, BAS retains valuable bioactive compounds, including sulfated [...] Read more.
Due to large-scale macroalgal blooms, nutrient enrichment, and changes in ocean circulation brought on by climate change, beach-accumulated seaweed (BAS) has quickly become a global environmental and waste-governance concern. Despite degradation and contamination during beach stranding, BAS retains valuable bioactive compounds, including sulfated polysaccharides, phlorotannins, pigments, proteins, peptides, and lipids, which exhibit anti-inflammatory, antioxidant, antimicrobial, antiviral, immunomodulatory, anticancer, and metabolic regulatory activities. This review critically evaluates BAS as a sustainable bioresource by integrating current knowledge on biomass composition, degradation-associated challenges, bioactive properties, valorization pathways, advanced extraction technologies, safety validation, regulatory considerations, and emerging commercialization opportunities. Attention is given to sustainable valorization pathways, ranging from composting and bioenergy production to the recovery of high-value bioactives through enzyme-assisted, green, and advanced extraction technologies. The review further discusses policy and regulatory gaps, contamination challenges, safety validation requirements, and life-cycle sustainability considerations that currently limit industrial adoption. Finally, emerging opportunities involving metabolomics, microbial bioprocessing, artificial intelligence, automation, and nanotechnology are explored as future directions for transforming BAS into a standardized and economically viable feedstock within the circular blue bioeconomy. Establishing harmonized regulatory frameworks and integrating BAS management with Sustainable Development Goals (SDGs) 12 and 14 will be critical for enabling sustainable resource recovery and long-term coastal resilience. Full article
(This article belongs to the Special Issue Coastal Waste Recycling: From Beach Collection to Circular Economy)
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26 pages, 8022 KB  
Article
Genome-Wide Identification and Expression Analysis of the Thaumatin-like Protein Genes in Filipendula ulmaria under Bipolaris sorokiniana Infection
by Ekaterina A. Istomina, Marina P. Slezina and Tatyana I. Odintsova
Curr. Issues Mol. Biol. 2026, 48(6), 640; https://doi.org/10.3390/cimb48060640 - 20 Jun 2026
Viewed by 396
Abstract
Pathogenesis-related (PR) proteins are crucial for plant defense against pathogen infection. However, the specific role of thaumatin-like proteins (TLPs), which comprise the PR-5 family, in plant immune responses has not been thoroughly investigated. Filipendula ulmaria is a medicinal plant with valuable pharmacological properties, [...] Read more.
Pathogenesis-related (PR) proteins are crucial for plant defense against pathogen infection. However, the specific role of thaumatin-like proteins (TLPs), which comprise the PR-5 family, in plant immune responses has not been thoroughly investigated. Filipendula ulmaria is a medicinal plant with valuable pharmacological properties, including antimicrobial, anti-inflammatory, gastroprotective, immunomodulatory, and anticancer activities. The structure of the TLP family and its role in the immune system of meadowsweet have not been studied so far. The goal of this study was to analyze in detail the TLP gene family in meadowsweet and explore its response to fungal infection. In the meadowsweet genome, we identified 27 putative TLP genes, examined their structure and location on chromosomes, analyzed cis-regulatory elements in the promoter regions, predicted the structure and physicochemical characteristics of the encoded proteins, and performed a phylogenetic analysis. We also studied the differential expression of TLP genes under Bipolaris sorokiniana infection. Of six differentially expressed genes, three genes were up-regulated 48 h post-infection, suggesting their involvement in defense response to the fungus. The results obtained shed light on the role of the TLP gene family in the immune system of F. ulmaria and form the foundation for the creation of disease-resistant crops in agriculture and the development of bio-based antimicrobials in medicine. Full article
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32 pages, 2918 KB  
Review
Plant-Derived Peptide–Polymer Therapeutics for Cutaneous Infections and Inflammation: Mechanistic Basis, Delivery Design and Translational Considerations
by Adnan Amin, Mozaniel Santana de Oliveira, Touseef Nawaz and Oberdan Oliveira Ferreira
Pharmaceutics 2026, 18(6), 729; https://doi.org/10.3390/pharmaceutics18060729 - 12 Jun 2026
Viewed by 741
Abstract
Cutaneous infections and chronic inflammatory wounds remain difficult to treat because antimicrobial resistance, polymicrobial biofilms, excessive protease activity, oxidative stress, and impaired barrier repair collectively reduce the effectiveness of conventional topical therapies. Plant-derived antimicrobial peptides (AMPs) and peptide-associated bioactives offer antimicrobial, antibiofilm, immunomodulatory, [...] Read more.
Cutaneous infections and chronic inflammatory wounds remain difficult to treat because antimicrobial resistance, polymicrobial biofilms, excessive protease activity, oxidative stress, and impaired barrier repair collectively reduce the effectiveness of conventional topical therapies. Plant-derived antimicrobial peptides (AMPs) and peptide-associated bioactives offer antimicrobial, antibiofilm, immunomodulatory, and tissue reparative potential; however, their clinical translation is limited by proteolytic instability, poor stratum corneum penetration, short cutaneous residence time, formulation variability, cytotoxicity risks and limited human evidence. The key research gap is the lack of an integrated translational framework linking plant-derived peptide bioactivity with polymer engineering, advanced delivery systems, skin microenvironment biology, manufacturability, and regulatory feasibility. This review aims to critically evaluate the design principles, therapeutic mechanisms, delivery platforms, and translational barriers of plant-based peptide–polymer therapeutics for cutaneous infection and inflammation. We summarize major classes of plant-derived antimicrobial peptides, including defensins, cyclotides, thionins, hevein-like peptides, snakins, lipid transfer proteins, and knottin-type scaffolds, and examine engineering strategies such as self-assembly, aromatic N-capping, PEGylation, lipidation, dendritic architectures, and stimuli-responsive conjugation. We further discuss topical matrices, nanocarriers, liposomes, electrospun fibers, and surface-tethered biomaterials as delivery platforms for improving peptide stability, local retention, and controlled release. Finally, we identify key translational bottlenecks, including selectivity, toxicity, scalability, batch reproducibility, regulatory classification, and insufficient clinical validation. Mechanism-driven peptide optimization, quality-by-design manufacturing, standardized preclinical models, and controlled clinical trials will be essential for advancing these systems toward safe and effective dermatological therapies. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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17 pages, 838 KB  
Article
The Combined Use of Ozone and Negative Pressure Wound Therapy in the Management of Diabetes-Related Foot Disease: A Retrospective Exploratory Cohort Study
by Izabella Kuźmiuk-Glembin, Agnieszka Białomyzy, Michał Sadowski, Bogdan Biedunkiewicz, Leszek Tylicki and Tomasz Niewęgłowski
Medicina 2026, 62(5), 827; https://doi.org/10.3390/medicina62050827 - 27 Apr 2026
Viewed by 705
Abstract
Background and Objectives: Diabetes mellitus (DM) is a major global health concern, with diabetes-related foot disease (DFD) representing one of its most severe complications, often resulting in chronic infection, osteomyelitis, and limb amputation. Conventional therapies frequently fail in refractory cases, necessitating novel [...] Read more.
Background and Objectives: Diabetes mellitus (DM) is a major global health concern, with diabetes-related foot disease (DFD) representing one of its most severe complications, often resulting in chronic infection, osteomyelitis, and limb amputation. Conventional therapies frequently fail in refractory cases, necessitating novel adjunctive strategies. Ozone therapy (OT) possesses antimicrobial, immunomodulatory, and oxygen-enhancing properties, while negative pressure wound therapy (NPWT) facilitates granulation, exudate removal, and tissue perfusion. This study explored the combined efficacy of OT and NPWT in advanced DFD. Materials and Methods: An exploratory, retrospective, observational cohort study was conducted at a specialized wound care center in Gdańsk, Poland, between 2019 and 2022. The study included 30 patients (n = 30) with refractory DFD involving both soft tissue and bone infection who had not responded to previous conventional treatment. The analyzed treatment approach consisted of surgical debridement, application of topical ozonated preparations, and (NPWT) with instillation of ozonated saline administered over a six-week period. Clinical outcomes included wound healing assessed using the Wagner classification and wound volume reduction, pain intensity measured using the Numeric Rating Scale (NRS), inflammatory biomarkers (C-reactive protein [CRP] and procalcitonin [PCT]), and microbiological characteristics of wound cultures. Statistical analyses were performed using the Wilcoxon signed-rank test and the chi-square test, and regression modeling was applied to identify potential predictors of therapeutic response. Statistical significance was defined as p < 0.05. Results: By week six, 100% of ulcers improved to Wagner stage ≤1, with 26.7% achieving stage 0. Median wound volume decreased from 5.5 cm3 to 0 cm3 (p < 0.001). Pain scores declined from 7.2 ± 0.96 points to 0.2 ± 0.5 points (p < 0.001). CRP and PCT levels decreased significantly (p < 0.001), and microbiological clearance was observed in all cases. Higher body mass index (BMI) was associated with poorer pain reduction. Conclusions: The combination of standard wound care with OT and NPWT was associated with clinically relevant improvements in wound healing, infection control, systemic inflammation, and pain reduction in patients with refractory DFD. Although limited by a non-controlled design and small cohort size, these findings support further randomized controlled trials to define the role of this combined approach in integrated diabetic foot care. Full article
(This article belongs to the Special Issue New Insights into Diabetes Complications—Diabetic Foot)
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18 pages, 3783 KB  
Article
Dual Immunomodulatory and Anti-Virulence Mechanisms of Curcumin Against Salmonella enterica Infection in Broilers: An Integrated Network Pharmacology and Molecular Docking Study
by Muhammad Jabbar, Mohamed Tharwat, Muhammad Younus, Muhammad Tariq, Abdallah A. Mousa and Saleh Alkhedhairi
Vet. Sci. 2026, 13(4), 406; https://doi.org/10.3390/vetsci13040406 - 20 Apr 2026
Viewed by 1381
Abstract
Salmonella enterica infection remains a major threat to poultry health and food safety, largely due to its ability to invade the intestinal epithelium, modulate host immunity, and persist intracellularly. Curcumin, a bioactive phytochemical, has shown promising antimicrobial and immunomodulatory potential; however, its [...] Read more.
Salmonella enterica infection remains a major threat to poultry health and food safety, largely due to its ability to invade the intestinal epithelium, modulate host immunity, and persist intracellularly. Curcumin, a bioactive phytochemical, has shown promising antimicrobial and immunomodulatory potential; however, its precise molecular interplay with host and pathogen systems remains unclear. An integrated computational pipeline was applied, combining target prediction, host immune network construction, Salmonella virulence interaction analysis, STRING-based PPI mapping, KEGG/GO enrichment, and molecular docking validation. Host immune hub genes and Salmonella virulence regulators were identified, followed by docking of curcumin to key host (AKT1, STAT3, TNF) and pathogen proteins (invA, phoP, ssrB). Host network analysis revealed enrichment in the PI3K–AKT, NF-κB, FoxO, and IL-10 signaling pathways, indicating roles in epithelial protection, immune regulation, inflammation suppression, and antioxidant defense. Salmonella virulence hubs were primarily associated with epithelial invasion, Type III secretion, intracellular survival, and global virulence reg-ulation. Docking analysis demonstrated a strong binding affinity of curcumin toward AKT1 (−7.4 kcal/mol), STAT3 (−6.5 kcal/mol) and TNF (−5.8 kcal/mol), supporting host immunomodulation and epithelial protection. Simultaneously, curcumin showed notable affinity for phoP (−6.8 kcal/mol), invA (−6.3 kcal/mol), and ssrB (−5.8 kcal/mol), suggesting the potential suppression of virulence signaling, invasion machinery, and intracellular persistence. This integrated host–pathogen systems analysis demonstrates that curcumin exerts a dual regulatory effect by enhancing host immune protection while concurrently disrupting Salmonella virulence mechanisms. These findings provide mechanistic insight supporting curcumin as a promising natural therapeutic candidate for controlling Salmonella infection in broilers. Full article
(This article belongs to the Topic Advances in Infectious and Parasitic Diseases of Animals)
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38 pages, 10121 KB  
Review
Mushrooms as Sustainable Protein Alternatives: Nutritional–Functional Characterization and Innovative Applications in Meat Analogs, Functional Snacks, and Beverages
by Subhash V. Pawde, Samart Sai-Ut, Passakorn Kingwascharapong, Jaksuma Pongsetkul, Shusong Wu, Jia-Qiang Huang, Zhaoxian Huang, Young Hoon Jung and Saroat Rawdkuen
Foods 2026, 15(8), 1301; https://doi.org/10.3390/foods15081301 - 9 Apr 2026
Cited by 1 | Viewed by 2651
Abstract
Global demand for sustainable protein has intensified amid environmental, public health, and ethical concerns surrounding conventional animal agriculture. Edible mushrooms have emerged as promising next-generation protein sources, delivering 19–35% protein (dry weight) with complete essential amino acid profiles and digestibility rates of 60–80%. [...] Read more.
Global demand for sustainable protein has intensified amid environmental, public health, and ethical concerns surrounding conventional animal agriculture. Edible mushrooms have emerged as promising next-generation protein sources, delivering 19–35% protein (dry weight) with complete essential amino acid profiles and digestibility rates of 60–80%. Beyond protein, mushrooms provide bioactive compounds, including β-glucans, ergothioneine, phenolic acids, and vitamin D2, supporting immunomodulatory, antioxidant, and anti-inflammatory functions. Enzymatically derived bioactive peptides further demonstrate antihypertensive and antimicrobial activity. This review systematically examines mushroom protein properties, processing technologies, and product performance across three application categories: meat analogs, functional snacks, and beverages. Advanced processing technologies including high-moisture extrusion, ultrasonic-assisted extraction, and microencapsulation have improved bioactive preservation and digestibility. From an environmental perspective, mushroom cultivation requires 85–90% less water and land than animal agriculture, with 80% fewer greenhouse gas emissions. However, critical gaps remain: extraction efficiency varies 3-fold across studies, only 15–23% of commercial products are supported by clinical trials, and techno-economic analyses are largely absent. Standardized processing protocols, large-scale clinical validation, and harmonized quality standards are essential to establish mushrooms as viable, commercially scalable protein alternatives. Full article
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24 pages, 865 KB  
Review
Applied Advances in Whey Bioactive Peptides: Enzymatic Generation, Mechanisms of Action, and Health-Related Applications
by Génesis K. González-Quijano, José Roberto González-Reyes, Ilse Monroy-Rodríguez, Esmeralda Rangel-Vargas, Ciro Baruchs Muñoz-Llandes and Fabiola Araceli Guzmán-Ortiz
Appl. Biosci. 2026, 5(2), 30; https://doi.org/10.3390/applbiosci5020030 - 7 Apr 2026
Viewed by 1409
Abstract
Whey is a major by-product of the dairy industry and represents a valuable source of proteins that can be enzymatically converted into bioactive peptides with diverse health-related functions. In recent years, increasing attention has been given to whey-derived peptides due to their antioxidant, [...] Read more.
Whey is a major by-product of the dairy industry and represents a valuable source of proteins that can be enzymatically converted into bioactive peptides with diverse health-related functions. In recent years, increasing attention has been given to whey-derived peptides due to their antioxidant, antihypertensive, antimicrobial, anti-inflammatory, antithrombotic, immunomodulatory, and anticancer activities, highlighting their potential use as functional ingredients and nutraceutical compounds. The generation and biological functionality of these peptides are strongly influenced by the protein source, processing conditions, enzymatic or microbial hydrolysis strategies, and peptide structure. Unlike the existing literature, this review provides an analysis of individual peptide sequences, meticulously linking their specific chemical structures to their diverse biological activities, such as antioxidants, antihypertensive, and immunomodulatory effects. By moving beyond general protein hydrolysis, this work offers a unique comparative framework that evaluates how these distinct peptide fractions perform under industrial conditions. Furthermore, it bridges the gap between laboratory discovery and commercial implementation, focusing on critical parameters for large-scale production, stability in functional food matrices, and the regulatory pathways required for market-ready nutraceuticals. This integrated approach provides a strategic roadmap for translating molecular bioactivity into high-value industrial applications. This review provides an applied overview of recent advances in the production of whey bioactive peptides, emphasizing enzymatic generation methods, structure–activity relationships, and underlying mechanisms of action associated with their biological effects. In addition, current and emerging applications of whey-derived peptides in functional foods, nutraceuticals, and health-oriented formulations are critically discussed. Finally, key challenges related to peptide stability, bioavailability, industrial scalability, and regulatory aspects are addressed to identify future perspectives for the effective translation of whey bioactive peptides from research to practical applications. Full article
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14 pages, 1810 KB  
Article
Biological Functions of Silver Nanowires in Inhibiting Vibrio Pathogens and Modulating Shrimp Hemocyte Immunity
by Smruti R. Sahoo, Zhen-Hao Liao and Fan-Hua Nan
Life 2026, 16(4), 545; https://doi.org/10.3390/life16040545 - 26 Mar 2026
Viewed by 817
Abstract
Silver nanoparticle (AgNP)-based products have been increasingly applied in aquaculture due to their antimicrobial properties and capacity to modulate host immunity. This study investigated the biological activities of synthesized silver nanowires (AgNWs), with particular emphasis on their anti-Vibrio efficacy and immunomodulatory effects, [...] Read more.
Silver nanoparticle (AgNP)-based products have been increasingly applied in aquaculture due to their antimicrobial properties and capacity to modulate host immunity. This study investigated the biological activities of synthesized silver nanowires (AgNWs), with particular emphasis on their anti-Vibrio efficacy and immunomodulatory effects, to evaluate their potential application in shrimp aquaculture. Antibacterial activity was assessed using nonlinear regression analysis to determine minimum inhibitory concentrations (MICs) against three major Vibrio pathogens, while cytotoxicity and immune responses were evaluated using white shrimp hemocytes through cell viability assays and in vitro gene expression analysis, respectively. AgNWs exhibited antibacterial effects on Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi, with MIC values of 873.7, 58.78, and 672.1 μg/mL, respectively. Hemocyte viability remained above 90% at AgNW concentrations of up to 1000 mg/L, indicating good biocompatibility. AgNWs significantly upregulated immune-related lipopolysaccharide and β-1,3-glucan-binding protein (LGBP) and Toll gene expression at specific concentrations, indicating immunostimulation. These results suggest that AgNWs possess antibacterial activity and immunomodulatory potential with low cytotoxicity, supporting their promise as a novel functional agent for shrimp disease management. Full article
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Article
Design and Screening of the Peptide SAMP-12aa Derived from LL-37, Which Exhibits Anti-H. Pylori Activity and Immunomodulatory Effects
by Jianliang Lu, Qingyu Wang, Meisong Qin, Jinfeng Dou, Youyi Xiong and Xiaolin Zhang
Molecules 2026, 31(6), 1002; https://doi.org/10.3390/molecules31061002 - 17 Mar 2026
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Abstract
The appearance of antibiotic-resistant strains of Helicobacter pylori (H. pylori) is leading to a decreased eradication rate of H. pylori infection. There is an urgent need to find new agents with antimicrobial mechanisms different from those of antibiotics, with therapeutic potential [...] Read more.
The appearance of antibiotic-resistant strains of Helicobacter pylori (H. pylori) is leading to a decreased eradication rate of H. pylori infection. There is an urgent need to find new agents with antimicrobial mechanisms different from those of antibiotics, with therapeutic potential to clear colonization of H. pylori in the stomach. Some antimicrobial peptides (AMPs) possess bactericidal activity by enhancing the permeability of the outer membrane and damaging the integrity of the cell membrane. Bacteria are not susceptible to drug resistance through this antimicrobial mechanism. In this study, 28 short peptides containing 12 amino acid residues were designed based on nine amino acid fragments (KRIVQRIKD) from human cathelicidin LL-37, which is stable in gastric juice, and 3 amino acids were added at the C-terminus of the peptide. These designed peptides were not digested and degraded by pepsin at low pH values. The peptides were predicted using the online tool platform. Then, the strongest antimicrobial peptide, named SAMP-12aa (KRIVQRIKDVIR), was screened from 28 short peptides. Further studies found that SAMP-12aa retained anti-H. pylori activity after incubation in simulated gastric juice. The MIC and MBC of SAMP-12aa were 8 μg/mL and 32 μg/mL, respectively. SAMP-12aa showed good bactericidal kinetics. SAMP-12aa was found to have cell selectivity, penetrating and damaging bacterial cell membranes and exhibiting almost no toxicity to human cells at a relatively high concentration (128 μg/mL). Regulatory T (Treg) cells express CD25High with immunosuppressive activity that induces immune tolerance in response to H. pylori. Molecular docking prediction revealed that SAMP-12aa could target the active center of Foxp3. Flow cytometry analysis revealed that SAMP-12aa can inhibit Foxp3 activity and downregulate CD25 protein expression on CD4+ T cells, thereby reducing the development and differentiation of CD4+Foxp3+CD25High Treg cells with immunosuppressive effects. Further research revealed that the levels of the cytokine interferon-γ (IFN-γ), which activates CD8+ T-cell activity, were significantly elevated, and the levels of transforming growth factor-β (TGF-β), which inhibits CD8+ T-cell activity, were significantly reduced. The results of this study reveal that SAMP-12aa not only possesses antibacterial activity but also has immunomodulatory effects. Full article
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