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Keywords = peptide synergy

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27 pages, 6274 KiB  
Article
Synergistic Antimicrobial Activity of BrSPR20-P1 Peptide and Silver Nanoparticles Against Pathogenic Bacteria
by Thanyamai Thongin, Somchai Sawatdee, Nuttapon Songnaka, Jumpei Uchiyama, Theanchai Wiwasuku, Teerapol Srichana, Titpawan Nakpheng and Apichart Atipairin
Int. J. Mol. Sci. 2025, 26(16), 7832; https://doi.org/10.3390/ijms26167832 - 13 Aug 2025
Viewed by 382
Abstract
Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, [...] Read more.
Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 µg/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 µg/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10× MIC, with killing rates during the first 3 h ranging from 4.04 ± 0.01 to 4.31 ± 0.03 h−1. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 µg/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 µg/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. Full article
(This article belongs to the Special Issue Antimicrobial Nanomaterials: Approaches, Strategies and Applications)
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14 pages, 3410 KiB  
Article
Gut Hormones and Postprandial Metabolic Effects of Isomaltulose vs. Saccharose Consumption in People with Metabolic Syndrome
by Jiudan Zhang, Dominik Sonnenburg, Stefan Kabisch, Stephan Theis, Margrit Kemper, Olga Pivovarova-Ramich, Domenico Tricò, Sascha Rohn and Andreas F. H. Pfeiffer
Nutrients 2025, 17(15), 2539; https://doi.org/10.3390/nu17152539 - 1 Aug 2025
Viewed by 338
Abstract
Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). [...] Read more.
Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). This study aimed to assess the most effective preprandial interval of ISO- or saccharose (SUC) snacks (1 h vs. 3 h preload) to enhance prandial incretin responses to a subsequent meal. Methods: In a randomized crossover design, 15 participants with MetS completed four experimental conditions on four non-consecutive days, combining two preload types (ISO or SUC) and two preload timings (Intervention A: 3 h preload; Intervention B: 1 h preload). Specifically, the four conditions were (1) ISO + Intervention A, (2) SUC + Intervention A, (3) ISO + Intervention B, and (4) SUC + Intervention B. The order of conditions was randomized and separated by a 3–7-day washout period to minimize carryover effects. On each study day, participants consumed two mixed meal tests (MMT-1 and MMT-2) with a standardized preload (50 g ISO or SUC) administered either 3 h or 1 h prior to MMT-2. Blood samples were collected over 9 h at 15 predefined time points for analysis of glucose, insulin, C-peptide, and incretin hormones (GLP-1, GIP, and PYY). Results: The unique digestion profile of ISO resulted in a blunted glucose ascent rate (ΔG/Δt: 0.28 vs. 0.53 mmol/L/min for SUC, p < 0.01), paralleled by synonyms PYY elevation over 540 min monitoring, compared with SUC. ISO also led to higher and more sustained GLP-1 and PYY levels, while SUC induced a stronger GIP response. Notably, the timing of ISO consumption significantly influenced PYY secretion, with the 3 h preload showing enhanced PYY responses and a more favorable SME compared to the 1 h preload. Conclusions: ISO, particularly when consumed 3 h before a meal (vs. 1 h), offers significant advantages over SUC by elevating PYY levels, blunting the glucose ascent rate, and sustaining GLP-1 release. This synergy enhances the second meal effect, suggesting ISO’s potential for managing postprandial glycemic excursions in MetS. Full article
(This article belongs to the Section Nutrition and Metabolism)
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30 pages, 1661 KiB  
Review
Gut Hormones and Inflammatory Bowel Disease
by Jonathan Weng and Chunmin C. Lo
Biomolecules 2025, 15(7), 1013; https://doi.org/10.3390/biom15071013 - 14 Jul 2025
Viewed by 809
Abstract
Obesity-driven inflammation disrupts gut barrier integrity and promotes inflammatory bowel disease (IBD). Emerging evidence highlights gut hormones—including glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), and apolipoprotein A4 (APOA4)—as key regulators of metabolism and mucosal immunity. [...] Read more.
Obesity-driven inflammation disrupts gut barrier integrity and promotes inflammatory bowel disease (IBD). Emerging evidence highlights gut hormones—including glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), and apolipoprotein A4 (APOA4)—as key regulators of metabolism and mucosal immunity. This review outlines known mechanisms and explores therapeutic prospects in IBD. GLP-1 improves glycemic control, induces weight loss, and preserves intestinal barrier function, while GLP-2 enhances epithelial repair and reduces pro-inflammatory cytokine expression in animal models of colitis. GIP facilitates lipid clearance, enhances insulin sensitivity, and limits systemic inflammation. PYY and CCK slow gastric emptying, suppress appetite, and attenuate colonic inflammation via neural pathways. APOA4 regulates lipid transport, increases energy expenditure, and exerts antioxidant and anti-inflammatory effects that alleviate experimental colitis. Synergistic interactions—such as GLP-1/PYY co-administration, PYY-stimulated APOA4 production, and APOA4-enhanced CCK activity—suggest that multi-hormone combinations may offer amplified therapeutic benefits. While preclinical data are promising, clinical evidence supporting gut hormone therapies in IBD remains limited. Dual GIP/GLP-1 receptor agonists improve metabolic and inflammatory parameters, but in clinical use, they are associated with gastrointestinal side effects that warrant further investigation. Future research should evaluate combination therapies in preclinical IBD models, elucidate shared neural and receptor-mediated pathways, and define optimal strategies for applying gut hormone synergy in human IBD. These efforts may uncover safer, metabolically tailored treatments for IBD, particularly in patients with coexisting obesity or metabolic dysfunction. Full article
(This article belongs to the Special Issue Metabolic Inflammation and Insulin Resistance in Obesity)
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17 pages, 572 KiB  
Article
Synthetic Human Lactoferrin Peptide hLF(1-11) Shows Antifungal Activity and Synergism with Fluconazole and Anidulafungin Towards Candida albicans and Various Non-Albicans Candida Species, Including Candidozyma auris
by Carlo Brouwer, Youp van der Linden, Maria Rios Carrasco, Saleh Alwasel, Tarad Abalkhail, Fatimah O. Al-Otibi, Teun Boekhout and Mick M. Welling
Antibiotics 2025, 14(7), 671; https://doi.org/10.3390/antibiotics14070671 - 2 Jul 2025
Viewed by 691
Abstract
Introduction: Candidozyma auris (Cz. auris) has emerged globally, and diseases caused by it are associated with a mortality rate of 30–72%. This yeast is often multidrug-resistant and challenging to treat. A synthetic peptide, consisting of 11 amino acids of human lactoferrin [...] Read more.
Introduction: Candidozyma auris (Cz. auris) has emerged globally, and diseases caused by it are associated with a mortality rate of 30–72%. This yeast is often multidrug-resistant and challenging to treat. A synthetic peptide, consisting of 11 amino acids of human lactoferrin (hLF1-11), offers a new therapy that is active against Candida albicans, non-albicans Candida yeasts, as well as Cz. auris. The current study examined the susceptibility of clinically relevant Candida species to hLF(1-11) in vitro and investigated the synergistic interaction of this peptide with fluconazole (FLU) and anidulafungin (ANI). Methods: Susceptibility of the yeasts to hLF(1-11) was tested with a microdilution method to determine minimum inhibitory concentrations (MICs). A total of 59 strains belonging to 16 species of Candida or Candidozyma were tested. The treatment cohort included 20 strains of Cz. auris originating from six different countries. Results: Mean MIC values of all susceptible strains ranged from 16.66 ± 6.46 μg/mL to 45.83 ± 10.21 μg/mL. There were no statistical differences in the susceptibility of hLF(1-11) for Cz. auris across geographic origins. In the combinatory tests, drugs acting together, the fractional inhibitory concentration indexes [FIC] < 1.0, showed a synergistic or additive effect on the efficacy of FLU and ANI when used in combination with hLF(1-11). [FIC] indexes 1–2 were interpreted as intermediate. MIC values in combinatory use were 1–2 titer steps lower than when used alone. Conclusions: hLF(1-11) inhibits the growth of yeasts that belong to the genus Candida, including Cz. auris. The combinatory use may be further investigated to treat infections caused by resistant yeasts. Full article
(This article belongs to the Special Issue Bioactive Peptides and Their Antibiotic Activity)
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29 pages, 366 KiB  
Article
Video-Driven Artificial Intelligence for Predictive Modelling of Antimicrobial Peptide Generation: Literature Review on Advances and Challenges
by Jielu Yan, Zhengli Chen, Jianxiu Cai, Weizhi Xian, Xuekai Wei, Yi Qin and Yifan Li
Appl. Sci. 2025, 15(13), 7363; https://doi.org/10.3390/app15137363 - 30 Jun 2025
Viewed by 696
Abstract
How video-based methodologies and advanced computer vision algorithms can facilitate the development of antimicrobial peptide (AMP) generation models should be further reviewed, structural and functional patterns should be elucidated, and the generative power of in silico pipelines should be enhanced. AMPs have drawn [...] Read more.
How video-based methodologies and advanced computer vision algorithms can facilitate the development of antimicrobial peptide (AMP) generation models should be further reviewed, structural and functional patterns should be elucidated, and the generative power of in silico pipelines should be enhanced. AMPs have drawn significant interest as promising therapeutic agents because of their broad-spectrum efficacy, low resistance profile, and membrane-disrupting mechanisms. However, traditional discovery methods are hindered by high costs, lengthy synthesis processes, and difficulty in accessing the extensive chemical space involved in AMP research. Recent advances in artificial intelligence—especially machine learning (ML), deep learning (DL), and pattern recognition—offer game-changing opportunities to accelerate AMP design and validation. By integrating video analysis with computational modelling, researchers can visualise and quantify AMP–microbe interactions at unprecedented levels of detail, thereby informing both experimental design and the refinement of predictive algorithms. This review provides a comprehensive overview of these emerging techniques, highlights major breakthroughs, addresses critical challenges, and ultimately emphasises the powerful synergy between video-driven pattern recognition, AI-based modelling, and experimental validation in the pursuit of next-generation antimicrobial strategies. Full article
(This article belongs to the Section Computing and Artificial Intelligence)
19 pages, 6683 KiB  
Article
Bioinspired Co-Assembled Hydrogels Constructed from Marine Self-Assembling Peptides and Polyphenol Network: Antioxidant and Infected Wound Healing
by Chuhan Wang, Dingyi Yu, Wen Liu, Xiang Zhu, Hanzhe Zhang, Shuang Zheng and Jingdi Chen
Antioxidants 2025, 14(7), 785; https://doi.org/10.3390/antiox14070785 - 26 Jun 2025
Viewed by 590
Abstract
Infectious wounds pose formidable clinical challenges due to hypoxia, exacerbated inflammation, and persistent microbial colonization. To address this, we developed a bioinspired multifunctional hydrogel (PTDPs) through the in situ freeze-thaw co-assembly of polyvinyl alcohol (PVA), tea polyphenols (TP), polydopamine (PDA), and marine-derived self-assembling [...] Read more.
Infectious wounds pose formidable clinical challenges due to hypoxia, exacerbated inflammation, and persistent microbial colonization. To address this, we developed a bioinspired multifunctional hydrogel (PTDPs) through the in situ freeze-thaw co-assembly of polyvinyl alcohol (PVA), tea polyphenols (TP), polydopamine (PDA), and marine-derived self-assembling peptides (AAPs). The resultant PTDP hydrogel formed an intricate hydrogen-bonded network that enhanced mechanical robustness and substrate adhesion. TP and PDA synergistically confer potent antioxidant properties: TP scavenges radicals via phenolic hydroxyl groups while PDA enhances responsiveness to diverse radicals in hypoxic environments. Integrated with AAPs’ pro-regenerative functions and PDA’s broad-spectrum antimicrobial efficacy, this system generates therapeutic synergy. Characterization revealed outstanding physicochemical properties including tunable plasticity, high swelling ratios, and sustained hydration retention. In vitro studies demonstrated potent antioxidant activity, efficient inhibition of Staphylococcus aureus and Escherichia coli proliferation, and cytocompatibility facilitating endothelial cell migration/proliferation. In murine full-thickness infected wound models, the PTDP hydrogel significantly accelerated wound closure, enhanced neovascularization, and improved collagen deposition, underscoring its potential as an innovative therapeutic platform for infected and chronic wounds with strong translational prospects. Full article
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14 pages, 2719 KiB  
Article
Combinatorial Effects of CPP-Modified Antimicrobial Peptides: Synergistic and Additive Interactions Against Pathogenic Bacteria
by Oxana V. Galzitskaya, Sergey V. Kravchenko, Sergei Y. Grishin, Alena P. Zakhareva, Leila G. Mustaeva, Elena Y. Gorbunova, Alexey K. Surin and Viacheslav N. Azev
Int. J. Mol. Sci. 2025, 26(13), 5968; https://doi.org/10.3390/ijms26135968 - 21 Jun 2025
Viewed by 527
Abstract
The development of novel antimicrobial peptides (AMPs) with broad-spectrum activity represents a promising strategy to overcome multidrug resistance in pathogenic bacteria. In this study, we investigated the antimicrobial activity of three designed peptides—R44KS*, V31KS*, and R23FS*—engineered to [...] Read more.
The development of novel antimicrobial peptides (AMPs) with broad-spectrum activity represents a promising strategy to overcome multidrug resistance in pathogenic bacteria. In this study, we investigated the antimicrobial activity of three designed peptides—R44KS*, V31KS*, and R23FS*—engineered to incorporate an amyloidogenic fragment from the S1 protein of Staphylococcus aureus and one or two cell-penetrating peptide (CPP) fragments to enhance cellular uptake. The antimicrobial efficacy of these peptides and their combinations was assessed against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Bacillus cereus. The results demonstrated that all three peptides exhibited significant antibacterial activity in a concentration-dependent manner, with R44KS* being the most potent. Peptide combinations, particularly V31KS*/R23FS* and R44KS*/V31KS*, showed enhanced inhibitory effects and reduced minimum inhibitory concentrations (MICs), suggesting synergistic or additive interactions. Fractional inhibitory concentration index (FICI) analysis confirmed that most combinations exhibited synergy or additive effects. These findings highlight the potential of CPP-modified peptides as antimicrobial agents and underscore the importance of optimizing peptide combinations for therapeutic applications. Full article
(This article belongs to the Section Molecular Microbiology)
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23 pages, 4235 KiB  
Review
Recent Advances in the Development of Functional Nucleic Acid Biosensors Based on Aptamer-Rolling Circle Amplification
by Ce Liu and Wanchong He
Molecules 2025, 30(11), 2375; https://doi.org/10.3390/molecules30112375 - 29 May 2025
Viewed by 1146
Abstract
Aptamers are synthetic nucleic acids or peptides that exhibit high specificity and affinity for target molecules such as small molecules, proteins, or cells. Due to their ability to bind precisely to these targets, aptamers have found widespread use in bioanalytical and diagnostic applications. [...] Read more.
Aptamers are synthetic nucleic acids or peptides that exhibit high specificity and affinity for target molecules such as small molecules, proteins, or cells. Due to their ability to bind precisely to these targets, aptamers have found widespread use in bioanalytical and diagnostic applications. Rolling circle amplification (RCA) is an amplification technique that utilizes DNA or RNA templates, where circular primers are extended by polymerases to generate multiple repeated sequences, enabling highly sensitive detection of target molecules. The integration of aptamers with RCA offers significant advantages, enhancing both the specificity and sensitivity of detection while ensuring a fast and straightforward process. This synergy has already been widely applied across various fields, including fluorescence, microfluidics, visualization, and electrochemical technologies. Examples include molecular probe development, rapid detection of disease biomarkers, and environmental monitoring. Looking ahead, the aptamer-RCA platform holds great promise for advancing early disease diagnosis, precision medicine, and the development of nanosensors, driving innovation and new applications in these fields. Full article
(This article belongs to the Special Issue Functional Nanomaterials for Biosensors and Biomedicine Application)
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28 pages, 5232 KiB  
Article
Evaluation of the Synergistic Activity of Antimicrobial Peptidomimetics or Colistin Sulphate with Conventional Antifungals Against Yeasts of Medical Importance
by Shyam Kumar Mishra, Rajesh Kuppusamy, Christina Nguyen, Jennifer Doeur, Harleen Atwal, Samuel Attard, Kristian Sørensen, Jennifer S. Lin, Edgar H. H. Wong, Alex Hui, Annelise E. Barron, Naresh Kumar and Mark Willcox
J. Fungi 2025, 11(5), 370; https://doi.org/10.3390/jof11050370 - 12 May 2025
Viewed by 1510
Abstract
With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals [...] Read more.
With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals against Candida albicans, C. tropicalis, C. parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii and Kluyveromyces marxianus, and Candidozyma auris using the checkerboard microdilution test. RK758 was synergistic with fluconazole in 78% of isolates, with the remaining 22% of isolates still showing partial synergy; it showed synergy with amphotericin B in 56% of isolates, and with caspofungin, 78% of isolates exhibited either synergy or partial synergy. TM8 showed synergy with fluconazole in 44% (with partial synergy in another 44%) of isolates, with amphotericin B in 67% of isolates, and with caspofungin in 44% (with partial synergy in another 44%) of isolates. Colistin with fluconazole or caspofungin exhibited synergy or partial synergy in 56% of the isolates. No antagonism was observed in any of the combinations. Additionally, a time-kill assay further demonstrated synergistic activity between fluconazole and TM8 or RK758. The effects of these peptidomimetics on cell membrane integrity were demonstrated in an ergosterol binding assay, supported by SYTOX Green and cellular leakage assays, both indicating a lytic effect. These results suggest that peptidomimetics can synergise with conventional antifungals, offering a potential strategy for combination therapy against yeast infections. The membrane lytic activity of the peptidomimetics likely plays a role in their synergistic interaction with antifungals, thereby enhancing the antimicrobial activities of both compounds at sub-MIC levels. Full article
(This article belongs to the Special Issue Alternative Therapeutic Approaches of Candida Infections, 4th Edition)
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17 pages, 1593 KiB  
Article
Ethanolic Extract of Rosa rugosa Roots and Its Bioactive Compound, Oleamide, Prevented Amyloid β-Induced Oxidative Stress and Improved Behavioral Tests in Mice
by Chan Kyu Park, Soo Jung Choi, Cho Rong Kim, Hyo Ri Shin, Eui-Cheol Shin, Young Jun Kim, Tae Jin Cho, Dong-Hoon Shin and Jae Kyeom Kim
Int. J. Mol. Sci. 2025, 26(9), 4214; https://doi.org/10.3390/ijms26094214 - 29 Apr 2025
Viewed by 660
Abstract
Researchers have long focused on the accumulation of amyloid beta (Aβ) peptides in the brain as a primary pathological hallmark driving cognitive decline. This study investigated the neuroprotective effects of Rosa rugosa (RR) root extract and its key bioactive constituent, oleamide, against amyloid [...] Read more.
Researchers have long focused on the accumulation of amyloid beta (Aβ) peptides in the brain as a primary pathological hallmark driving cognitive decline. This study investigated the neuroprotective effects of Rosa rugosa (RR) root extract and its key bioactive constituent, oleamide, against amyloid beta (Aβ)-induced neurotoxicity. Initially, an ethanolic extract of RR root was screened via in vitro assays to assess antioxidant and cytoprotective potential in rat pheochromocytoma cells. Subsequent fractionation, open-column chromatography, and preparatory thin-layer chromatography led to the isolation of oleamide, confirmed by gas chromatography–mass spectrometry and 1H/13C nuclear magnetic resonance analyses. In vivo experiments using intracerebroventricularly injected Aβ in male mice demonstrated that both RR root extract and oleamide significantly improved cognitive performance in the Y-maze and passive avoidance tests. Additionally, oleamide restored acetylcholine levels and reduced malondialdehyde concentrations in brain tissue, indicating mitigation of oxidative stress and support of cholinergic function. No significant toxicity was observed, as evidenced by stable serum transaminase levels and unaltered body or brain weights. These findings highlight oleamide’s potential to protect against Aβ-driven pathology through multiple mechanisms, including reduced lipid peroxidation and improved neurotransmission. Further investigations into oleamide’s molecular targets and synergy with existing therapies may advance its development as a novel candidate for Alzheimer’s disease prevention or adjunct treatment. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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16 pages, 14665 KiB  
Article
The Membrane-Targeting Synergistic Antifungal Effects of Walnut-Derived Peptide and Salicylic Acid on Prickly Pear Spoilage Fungus
by Yue Hu, Na Liu, Caiqing Ma, Difeng Ren, Dujun Wang, Yueling Shang, Fengwei Li, Yongmei Lyu, Chen Cai, Long Chen, Wenjing Liu and Xiaohong Yu
Foods 2025, 14(6), 951; https://doi.org/10.3390/foods14060951 - 11 Mar 2025
Viewed by 868
Abstract
Fermented walnut (FW) meal exhibits antifungal activity against Penicillium victoriae (the fungus responsible for prickly pear spoilage), which is mainly attributed to the synergistic effect of antimicrobial peptides and salicylic acid (SA). This study aimed to investigate the synergistic mechanism between YVVPW (YW-5, [...] Read more.
Fermented walnut (FW) meal exhibits antifungal activity against Penicillium victoriae (the fungus responsible for prickly pear spoilage), which is mainly attributed to the synergistic effect of antimicrobial peptides and salicylic acid (SA). This study aimed to investigate the synergistic mechanism between YVVPW (YW-5, the peptide with the highest antifungal activity) and SA against the cell membrane of P. victoriae. Treatment enhanced prickly pear’s rot rate, polyphenol concentration, and superoxide dismutase (SOD) activity by 38.11%, 8.11%, and 48.53%, respectively, while reducing the microbial count by 19.17%. Structural analyses revealed β-sheets as YW-5′s predominant structure (41.18%), which increased to 49.0% during SA interaction. Molecular docking demonstrated YW-5′s stronger binding to β-(1,3)-glucan synthase and membrane protein amino acids via hydrogen bonds, hydrophobic forces, and π-π conjugate interactions. Spectroscopic analyses demonstrated SA’s major role in YW-5 synergy at the interface and polar head region of phospholipids, enhancing lipid chain disorder and the leakage of cell components. Malondialdehyde and SOD levels increased nearly two-fold and six-fold when treated with YW-5/SA, and YW-5 showed a more pronounced effect. Scanning electron and transmission electron microscopy confirmed that SA caused greater damage to spore morphology and cell ultrastructure. These findings support this formulation’s functions as an efficient antifungal substance in fruit storage. Full article
(This article belongs to the Section Food Quality and Safety)
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14 pages, 603 KiB  
Review
Functional Interactions Between Recombinant Serum Amyloid A1 (SAA1) and Chemokines in Leukocyte Recruitment
by Jo Van Damme, Sofie Struyf, Paul Proost, Ghislain Opdenakker and Mieke Gouwy
Int. J. Mol. Sci. 2025, 26(5), 2258; https://doi.org/10.3390/ijms26052258 - 3 Mar 2025
Cited by 1 | Viewed by 996
Abstract
The acute phase response is a hallmark of all inflammatory reactions and acute phase reactants, such as C-reactive protein (CRP) and serum amyloid A (SAA) proteins, are among the most useful plasma and serum markers of inflammation in clinical medicine. Although it is [...] Read more.
The acute phase response is a hallmark of all inflammatory reactions and acute phase reactants, such as C-reactive protein (CRP) and serum amyloid A (SAA) proteins, are among the most useful plasma and serum markers of inflammation in clinical medicine. Although it is well established that inflammatory cytokines, mainly interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) induce SAA in the liver, the biological functions of elicited SAA remain an enigma. By the classical multi-step protein purification studies of chemotactic factors present in plasma or serum, we discovered novel chemokines and SAA1 fragments, which are induced during inflammatory reactions. In contrast to earlier literature, pure SAA1 fails to induce chemokines, an ascribed function that most probably originates from contaminating lipopolysaccharide (LPS). However, intact SAA1 and fragments thereof synergize with CXC and CC chemokines to enhance chemotaxis. Natural SAA1 fragments are generated by inflammatory proteinases such as matrix metalloproteinase-9 (MMP-9). They mediate synergy with chemokines by the interaction with cognate G protein-coupled receptors (GPCRs), formyl peptide receptor 2 (FPR2) and (CC and CXC) chemokine receptors. In conclusion, SAA1 enforces the action of many chemokines and assists in local leukocyte recruitment, in particular, when the concentrations of specifically-induced chemokines are still low. Full article
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16 pages, 2387 KiB  
Article
In Vitro and In Vivo Evaluation of the De Novo Designed Antimicrobial Peptide P6.2 Against a KPC-Producing P. aeruginosa Clinical Isolate
by Melina M. B. Martinez, Merlina Corleto, Melanie Weschenfeller, Santiago Urrea Montes, Camila N. Salomón, Natalia Gonzalez, Matías Garavaglia, Diego Faccone and Paulo C. Maffía
Biomolecules 2025, 15(3), 339; https://doi.org/10.3390/biom15030339 - 27 Feb 2025
Cited by 1 | Viewed by 899
Abstract
The antimicrobial peptide P6.2 was previously de novo designed as an alpha helix cationic amphipathic molecule. In previous work, we have shown that this peptide displayed significant antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria. [...] Read more.
The antimicrobial peptide P6.2 was previously de novo designed as an alpha helix cationic amphipathic molecule. In previous work, we have shown that this peptide displayed significant antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria. However, while P6.2 lacked biofilm-inhibiting properties against the P. aeruginosa strain PA01, it displayed anti-inflammatory effects in a murine acute lung infection model challenged with this pathogen. In this work, the peptide P6.2 antimicrobial activity and its possible synergy with meropenem were evaluated both in vitro and in vivo using a Galleria mellonella infection model against a carbapenem-resistant KPC-producing clinical isolate of P. aeruginosa. Firstly, the cytotoxic effect of the peptide on A549 and RAW264.7 cell lines was assayed, showing no cytotoxicity at 64 µg/mL and below. Then, the MIC (minimal inhibitory concentration) and bactericidal effect against the carbapenemase-producing strain P. aeruginosa M13513 strain were determined. P6.2 showed a MIC between 32 and 64 µg/mL, and a rapid bactericidal activity against this strain (less than 45 min). The peptide stability at different temperatures and in bovine serum at 37 °C was also analyzed, showing good stability and almost no degradation after 15 min of incubation at 100 °C or 24 h at 37 °C in serum, respectively. The antibiofilm activity was also evaluated, and although the peptide did not show biofilm inhibitory activity, it did demonstrate biofilm disruptive activity, together with bactericidal activity inside the pre-formed biofilm. The possible synergistic effect with the carbapenem meropenem was then analyzed in vitro by killing kinetics, revealing a synergistic interaction between P6.2 and the antibiotic against this strain. Finally, P6.2 was evaluated in vivo in the Galleria mellonella larvae infection model. Interestingly, in G. mellonella, P6.2 alone did not completely clear the infection caused by P. aeruginosa M13513. However, when combined with meropenem, P6.2 demonstrated a synergistic effect, leading to increased survival rates in infected larvae. The results presented here highlight the potential that this peptide displays when used in combination with carbapenems against a clinically relevant KPC-producing P. aeruginosa. Full article
(This article belongs to the Special Issue State of the Art and Perspectives in Antimicrobial Peptides)
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12 pages, 5103 KiB  
Review
Recent Advances in Peptide Inhibitors Targeting Wild-Type Ras Protein Interactions in Cancer Therapy
by Weirong Qin, Zijian Liu, Mingyu Huang, Lin Liang, Yuxin Gan, Zubei Huang, Jin Huang and Xiangzan Wei
Int. J. Mol. Sci. 2025, 26(4), 1425; https://doi.org/10.3390/ijms26041425 - 8 Feb 2025
Cited by 2 | Viewed by 1451
Abstract
Ras proteins are pivotal in the regulation of cell proliferation signals, and their dysregulation is intricately linked to the pathogenesis of various malignancies. Peptide inhibitors hold distinct advantages in targeting Ras proteins, attributable to their extensive binding domains, which result from the smooth [...] Read more.
Ras proteins are pivotal in the regulation of cell proliferation signals, and their dysregulation is intricately linked to the pathogenesis of various malignancies. Peptide inhibitors hold distinct advantages in targeting Ras proteins, attributable to their extensive binding domains, which result from the smooth surfaces of the proteins. The array of specific strategies includes the employment of full hydrocarbon chains, cyclic peptides, linear peptides, and N-terminal nucleation polypeptides. These methods effectively suppress the Ras signaling pathway through distinct mechanisms, highlighting their potential as anti-neoplastic agents. Moreover, cutting-edge methodologies, including the N-terminal aspartate nucleation strategy and the utilization of hydrocarbon-stapled peptides, are transforming the landscape of therapeutics aimed at Ras proteins. These innovations highlight the promise of peptide libraries and combinatorial chemistry in augmenting binding affinity, specificity, and cellular permeability, which are pivotal for the development of potent anti-cancer agents. The incorporation of dual therapeutic strategies, such as the synergy between peptide inhibitors and conventional chemotherapy or the use of radiotherapy enhancers, emerges as a compelling strategy to bolster the efficacy of cancer treatments targeting the Ras-MAPK pathway. Furthermore, recent studies have demonstrated that Ras-targeting stabilized peptides can amplify the radio-sensitivity of cancer cells, offering an innovative approach to enhance the efficacy of radiation therapy within cancer management. Full article
(This article belongs to the Special Issue Anti-cancer Effects of Natural Products)
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13 pages, 628 KiB  
Article
Evaluation of the Synergistic Antimicrobial Activity of Essential Oils and Cecropin A Natural Peptide on Gram-Negative Bacteria
by Filippo Fratini, Chiara Pecorini, Ilaria Resci, Emma Copelotti, Francesca Paola Nocera, Basma Najar and Simone Mancini
Animals 2025, 15(2), 282; https://doi.org/10.3390/ani15020282 - 20 Jan 2025
Cited by 5 | Viewed by 1918
Abstract
In an era dominated by the phenomenon of antibiotic resistance, it is increasingly important to look for alternatives to synthetic antibiotics. In light of these considerations, the synergistic use of essential oils and Antimicrobial Peptides (AMPs) seems a viable strategy. In this study, [...] Read more.
In an era dominated by the phenomenon of antibiotic resistance, it is increasingly important to look for alternatives to synthetic antibiotics. In light of these considerations, the synergistic use of essential oils and Antimicrobial Peptides (AMPs) seems a viable strategy. In this study, we assessed the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Fractional Inhibitory Concentration (FIC) of three Essential Oils (EOs): winter savory (Satureja montana), bergamot (Citrus bergamia) and cinnamon (Cinnamomum zeylanicum) and of the insect antimicrobial peptide Cecropin A (CecA), alone and in combination with EOs, against two Gram-negative ATCC bacterial strains: Escherichia coli and Salmonella enterica serovar Typhimurium. The MIC results showed that winter savory EO (SmEO) and cinnamon EO (CzEO) exhibited the strongest antibacterial activity against both bacterial strains, whereas bergamot EO (CbEO) and CecA demonstrated comparatively lower antibacterial efficacy. These results were also confirmed by the MBC values. The FIC Indices (FICI) revealed that the most effective synergies were observed with the combinations SmEO/CzEO and SmEO/CbEO against E. coli, while against S. enterica Typhimurium the best combinations were CbEO/CzEO and SmEO/CzEO. Regarding CecA, although it was not the most efficient agent either individually or in combination, it is noteworthy that, when combined, it exhibited antibacterial activity even at a 1:64 dilution. Full article
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