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33 pages, 4665 KiB  
Review
A Paradigm Shift in SSTI Management: The Multifunctional Role of Extracellular Vesicles
by Barathan Muttiah and Alfizah Hanafiah
Int. J. Mol. Sci. 2025, 26(13), 6481; https://doi.org/10.3390/ijms26136481 - 5 Jul 2025
Viewed by 837
Abstract
Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle [...] Read more.
Skin and soft tissue infections (SSTIs) are becoming an urgent public health issue worldwide. The globe is facing a growing problem with drug-resistant germs, and current treatments are not quite cutting it. There is a real need for new therapies that can tackle these challenges more effectively. This brings us to an interesting question: Can extracellular vesicles (EVs) from different sources, such as mesenchymal stem cells (MSCs), immune cells, or even plants and animals, help in treating SSTIs, especially given the rise in drug resistance? Studies have shown that MSC-derived EVs are particularly noteworthy because they carry components such as antimicrobial peptides (AMPs) that can work together to fight infections, boost the immune response, and aid in healing. These vesicles play a role in how our body interacts with infections, helping to clear bacteria, reduce inflammation, and promote tissue repair. We also see that EVs from plants and bacteria can directly fight off germs, while those from animals can support the healing process of skin. Although early studies have shown promise for EV therapies, there are still hurdles to overcome, such as ensuring consistent production and delivery. This review looks at the potential of EVs as powerful agents in managing infections and supporting healing, highlighting an exciting area of research in medicine. Full article
(This article belongs to the Special Issue Extracellular Vesicles: Advances in Multi-Omics)
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27 pages, 3061 KiB  
Review
Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense
by Siti Balqis Adnan, Manira Maarof, Mh Busra Fauzi and Nur Izzah Md Fadilah
Int. J. Mol. Sci. 2025, 26(13), 5920; https://doi.org/10.3390/ijms26135920 - 20 Jun 2025
Cited by 4 | Viewed by 1813
Abstract
Although penicillin transformed antibiotic therapy, rising antimicrobial resistance (AMR) has limited its effectiveness, creating a need for new approaches in wound healing. Antimicrobial peptides (AMPs) are promising candidates due to their rapid membrane-disrupting action, immunomodulatory effects, and ability to target drug-resistant pathogens, though [...] Read more.
Although penicillin transformed antibiotic therapy, rising antimicrobial resistance (AMR) has limited its effectiveness, creating a need for new approaches in wound healing. Antimicrobial peptides (AMPs) are promising candidates due to their rapid membrane-disrupting action, immunomodulatory effects, and ability to target drug-resistant pathogens, though their specific roles in promoting wound healing are still not fully understood. This review aims to provide a comprehensive synthesis of the current evidence on the dual role of AMPs as both antimicrobial and immunomodulatory agents in the context of wound healing. Recent studies published between 2020 and 2025 were comprehensively reviewed, focusing on the mechanisms by which AMPs contribute to pathogen elimination, immune regulation, tissue repair, and inflammation resolution. AMPs not only exhibit rapid membrane-disruptive activities against a wide range of pathogens but also influence immune cell behavior, particularly by promoting macrophage polarization toward a reparative M2 phenotype, modulating cytokine and chemokine network, and maintaining T-cell homeostasis. Their ability to simultaneously control infection and regulate inflammation positions AMPs as promising candidates for advanced wound care strategies. The dual antimicrobial and immunomodulatory functions of AMPs represent a synergistic mechanism essential for effective wound recovery. Understanding and harnessing these properties can drive the development of innovative therapies, such as AMP-integrated smart biomaterials and targeted peptide delivery systems, offering new solutions for both acute and chronic wound management. Full article
(This article belongs to the Special Issue Regenerative Medicine: Biomaterials and Stem Cell Research)
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15 pages, 1725 KiB  
Review
Marine-Derived Antioxidants: A Comprehensive Review of Their Therapeutic Potential in Oxidative Stress-Associated Diseases
by Ruiqiu Zhang, Yuke Ren, Tianqi Ren, Yue Yu, Bo Li and Xiaobing Zhou
Mar. Drugs 2025, 23(6), 223; https://doi.org/10.3390/md23060223 - 22 May 2025
Cited by 1 | Viewed by 1387
Abstract
Oxidative stress is a critical factor contributing to the pathogenesis of numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions. In recent years, marine-derived antioxidants have emerged as promising therapeutic agents due to their unique biological activities and diverse sources. This comprehensive review [...] Read more.
Oxidative stress is a critical factor contributing to the pathogenesis of numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions. In recent years, marine-derived antioxidants have emerged as promising therapeutic agents due to their unique biological activities and diverse sources. This comprehensive review explores the therapeutic potential of various marine antioxidants in mitigating oxidative stress-associated diseases. Marine organisms are rich in bioactive compounds, such as polysaccharides, polyphenols, carotenoids, peptides, and vitamins, which exhibit potent antioxidant and free radical scavenging abilities. These compounds have been shown to effectively inhibit oxidative reactions, repair oxidative damage, and enhance the body’s antioxidant defense mechanisms. For instance, marine polysaccharides and their derivatives can scavenge reactive oxygen species (ROS), protect neurons from oxidative damage, and alleviate inflammation in neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases. Similarly, marine unsaturated fatty acids, such as omega-3 polyunsaturated fatty acids (PUFAs), have been found to reduce cardiovascular risks by lowering serum triglyceride levels and improving vascular endothelial function. Additionally, marine-derived superoxide dismutase (SOD) plays a crucial role in neutralizing ROS, thereby offering protection against oxidative stress in various diseases. Despite these promising findings, challenges remain in the field, including the need for improved extraction and purification technologies, more comprehensive activity evaluation systems, and further research into the safety and bioavailability of these compounds. This review provides a detailed overview of the current research status, highlighting the types, structural characteristics, antioxidant activities, and mechanisms of action of marine antioxidants. It also identifies key areas for future research and development, aiming to harness the full potential of marine-derived antioxidants in the prevention and treatment of oxidative stress-related diseases. Full article
(This article belongs to the Special Issue Marine Anti-inflammatory Agents )
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14 pages, 2280 KiB  
Article
The Efficacy of Remineralizing Materials on Artificial Enamel Lesions: An In Vitro Study
by Gustė Klimaitė, Arūnas Vasiliauskas, Pranas Grinkevičius, Dominyka Grinkevičienė and Deivydas Šapalas
Medicina 2025, 61(3), 462; https://doi.org/10.3390/medicina61030462 - 6 Mar 2025
Viewed by 1120
Abstract
Background and Objectives: Contemporary caries treatment seeks to preserve hard dental tissues as well as to promote lesion remineralization and biological tissue regeneration. While fluoride-based treatments remain the gold standard, their effectiveness has limitations, prompting interest in innovative remineralization technologies. Nano-hydroxyapatite (nano-HA) varnish [...] Read more.
Background and Objectives: Contemporary caries treatment seeks to preserve hard dental tissues as well as to promote lesion remineralization and biological tissue regeneration. While fluoride-based treatments remain the gold standard, their effectiveness has limitations, prompting interest in innovative remineralization technologies. Nano-hydroxyapatite (nano-HA) varnish and self-assembling peptide (SAP) P11-4 are promising biomimetic materials that promote enamel repair, yet long-term data on their efficacy are limited. The objectives of this study were to evaluate the effectiveness of nano-HA varnish and peptide P11-4 in restoring enamel surface hardness after artificial lesions in vitro and to compare them to a control group and fluoride varnish. Materials and Methods: Artificial enamel lesions were created on the buccal surfaces of 36 extracted human molars, which were randomly divided into four groups (n = 9): control, peptide P11-4, fluoride varnish, and nano-hydroxyapatite varnish. After applying the materials as per manufacturer instructions, specimens were stored in artificial saliva for 14 days. Enamel surface hardness was measured using the Vickers hardness test (HV) at baseline, after demineralization, and after remineralization. Statistical analysis was performed with “IBM SPSS 27.0” using non-parametric Kolmogorov–Smirnov, Kruskal–Wallis, Dunn’s, and Wilcoxon tests. Results: The mean baseline enamel hardness value was 323.95 (SD 33.47) HV. After 14 days of demineralization, the mean surface hardness of artificial enamel lesions significantly plummeted to 172.17 (SD 35.96) HV (p = 0.000). After 14 days of remineralization, the mean value significantly increased to 213.21 (SD 50.58) HV (p = 0.001). The results of the study revealed statistically significant enamel remineralization of the peptide P11-4 group in regard to the demineralized enamel (p < 0.05). In contrast, there were no significant results in other treatment groups (p > 0.05). Remineralization of enamel was the highest in samples from the P11-4 group (54.1%), followed by the nano-HA group (35.4%), FV group (17.8%), and control group (11.2%). There was a significant difference (p < 0.05) in the remineralizing ability between the peptide P11-4 and all other treatment groups. Conclusions: Self-assembling peptide P11-4 effectively remineralized artificial enamel lesions and proved to be significantly more effective compared to fluoride varnish and nano-hydroxyapatite varnish, showcasing its superior performance as a remineralizing agent. Full article
(This article belongs to the Topic Advances in Dental Materials)
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67 pages, 2138 KiB  
Review
Antioxidants to Defend Healthy and Youthful Skin—Current Trends and Future Directions in Cosmetology
by Anna Budzianowska, Katarzyna Banaś, Jaromir Budzianowski and Małgorzata Kikowska
Appl. Sci. 2025, 15(5), 2571; https://doi.org/10.3390/app15052571 - 27 Feb 2025
Cited by 7 | Viewed by 5450
Abstract
Antioxidants are indispensable in protecting the skin from oxidative stress caused by environmental factors such as ultraviolet (UV) radiation, pollution, and lifestyle-related influences. This review examines the essential role of antioxidants in modern cosmetology, highlighting their dual functionality as protective agents and active [...] Read more.
Antioxidants are indispensable in protecting the skin from oxidative stress caused by environmental factors such as ultraviolet (UV) radiation, pollution, and lifestyle-related influences. This review examines the essential role of antioxidants in modern cosmetology, highlighting their dual functionality as protective agents and active components in skincare formulations. Oxidative stress, primarily driven by an imbalance between reactive oxygen species (ROS) production and the skin’s defense mechanisms, accelerates aging processes, damages cellular structures, and compromises skin integrity. Antioxidants, whether natural or synthetic, act by neutralizing ROS, reducing inflammation, and promoting cellular repair, effectively mitigating these harmful effects. This comprehensive analysis synthesizes findings from 280 studies accessed via key databases, including PubMed, Scopus, and ScienceDirect. It investigates the biochemical mechanisms of antioxidant activity, emphasizing compounds such as vitamins (C, E, A), carotenoids, polyphenols, peptides, and minerals, alongside bioactive extracts derived from algae, fungi, lichens, and plants. Carotenoids, including ꞵ-carotene, lutein, lycopene, and astaxanthin, demonstrate potent antioxidant activity, making them crucial for photoprotection and anti-aging. Phenolic compounds, such as ferulic acid, resveratrol, hesperidin, and xanthohumol, play a significant role in neutralizing oxidative stress and improving skin health. This review also highlights bioactives from algae, fungi, and lichens. Algae, particularly microalgae like Haematococcus pluvialis, known for astaxanthin production, are highlighted for their extraordinary photoprotective and anti-aging properties. Brown algae (Fucus vesiculosus) and red algae (Porphyra) provide polysaccharides and bioactive molecules that enhance hydration and barrier function. Fungi contribute a wealth of antioxidant and anti-inflammatory compounds, including polysaccharides, ꞵ-glucans, and enzymes, which support cellular repair and protect against oxidative damage. Lichens, through unique phenolic metabolites, offer potent free-radical-scavenging properties and serve as effective ingredients in formulations targeting environmental stress. Plant-derived antioxidants offer a diverse range of benefits. Plant-derived antioxidants, such as flavonoids, phenolic acids, and carotenoids, further amplify skin resilience, hydration, and repair mechanisms, aligning with the growing demand for nature-inspired solutions in cosmetics. The integration of these diverse natural sources into cosmetic formulations reflects the industry’s commitment to sustainability, innovation, and efficacy. By harnessing the synergistic potential of bioactives from algae, fungi, lichens, and plants, modern cosmetology is advancing toward multifunctional, health-conscious, and eco-friendly products. Future research directions include optimizing delivery systems for these bioactives, enhancing their stability and bioavailability, and expanding their applications to meet evolving dermatological challenges. Full article
(This article belongs to the Special Issue Cosmetics Ingredients Research - 2nd Edition)
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24 pages, 872 KiB  
Review
Peptides Used for Heavy Metal Remediation: A Promising Approach
by Yingyong Luo, Yunfeng Zhang, Zhuang Xiong, Xiaodie Chen, Ajia Sha, Wenqi Xiao, Lianxin Peng, Liang Zou, Jialiang Han and Qiang Li
Int. J. Mol. Sci. 2024, 25(12), 6717; https://doi.org/10.3390/ijms25126717 - 18 Jun 2024
Cited by 12 | Viewed by 3484
Abstract
In recent years, heavy metal pollution has become increasingly prominent, severely damaging ecosystems and biodiversity, and posing a serious threat to human health. However, the results of current methods for heavy metal restoration are not satisfactory, so it is urgent to find a [...] Read more.
In recent years, heavy metal pollution has become increasingly prominent, severely damaging ecosystems and biodiversity, and posing a serious threat to human health. However, the results of current methods for heavy metal restoration are not satisfactory, so it is urgent to find a new and effective method. Peptides are the units that make up proteins, with small molecular weights and strong biological activities. They can effectively repair proteins by forming complexes, reducing heavy metal ions, activating the plant’s antioxidant defense system, and promoting the growth and metabolism of microorganisms. Peptides show great potential for the remediation of heavy metal contamination due to their special structure and properties. This paper reviews the research progress in recent years on the use of peptides to remediate heavy metal pollution, describes the mechanisms and applications of remediation, and provides references for the remediation of heavy metal pollution. Full article
(This article belongs to the Special Issue Innovative Molecular Strategies in Biomedicine)
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17 pages, 1337 KiB  
Review
Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration
by Angela Angjelova, Elena Jovanova, Alessandro Polizzi, Marco Annunziata, Ludovica Laganà, Simona Santonocito and Gaetano Isola
Medicina 2024, 60(5), 773; https://doi.org/10.3390/medicina60050773 - 7 May 2024
Cited by 12 | Viewed by 5210
Abstract
The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of [...] Read more.
The regeneration of periodontal bone defects continues to be an essential therapeutic concern in dental biomaterials. Numerous biomaterials have been utilized in this sector so far. However, the immune response and vascularity in defect regions may be disregarded when evaluating the effectiveness of biomaterials for bone repair. Among several regenerative treatments, the most recent technique of in situ tissue engineering stands out for its ability to replicate endogenous restorative processes by combining scaffold with particular growth factors. Regenerative medicine solutions that combine biomaterials/scaffolds, cells, and bioactive substances have attracted significant interest, particularly for bone repair and regeneration. Dental stem cells (DSCs) share the same progenitor and immunomodulatory properties as other types of MSCs, and because they are easily isolable, they are regarded as desirable therapeutic agents in regenerative dentistry. Recent research has demonstrated that DSCs sown on newly designed synthetic bio-material scaffolds preserve their proliferative capacity while exhibiting increased differentiation and immuno-suppressive capabilities. As researchers discovered how short peptide sequences modify the adhesion and proliferative capacities of scaffolds by activating or inhibiting conventional osteogenic pathways, the scaffolds became more effective at priming MSCs. In this review, the many components of tissue engineering applied to bone engineering will be examined, and the impact of biomaterials on periodontal regeneration and bone cellular biology/molecular genetics will be addressed and updated. Full article
(This article belongs to the Section Dentistry and Oral Health)
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31 pages, 3629 KiB  
Review
Inflammasome Molecular Insights in Autoimmune Diseases
by Monica Neamțu, Veronica Bild, Alexandru Vasincu, Oana Dana Arcan, Delia Bulea, Daniela-Carmen Ababei, Răzvan-Nicolae Rusu, Ioana Macadan, Ana Maria Sciucă and Andrei Neamțu
Curr. Issues Mol. Biol. 2024, 46(4), 3502-3532; https://doi.org/10.3390/cimb46040220 - 18 Apr 2024
Cited by 14 | Viewed by 4850
Abstract
Autoimmune diseases (AIDs) emerge due to an irregular immune response towards self- and non-self-antigens. Inflammation commonly accompanies these conditions, with inflammatory factors and inflammasomes playing pivotal roles in their progression. Key concepts in molecular biology, inflammation, and molecular mimicry are crucial to understanding [...] Read more.
Autoimmune diseases (AIDs) emerge due to an irregular immune response towards self- and non-self-antigens. Inflammation commonly accompanies these conditions, with inflammatory factors and inflammasomes playing pivotal roles in their progression. Key concepts in molecular biology, inflammation, and molecular mimicry are crucial to understanding AID development. Exposure to foreign antigens can cause inflammation, potentially leading to AIDs through molecular mimicry triggered by cross-reactive epitopes. Molecular mimicry emerges as a key mechanism by which infectious or chemical agents trigger autoimmunity. In certain susceptible individuals, autoreactive T or B cells may be activated by a foreign antigen due to resemblances between foreign and self-peptides. Chronic inflammation, typically driven by abnormal immune responses, is strongly associated with AID pathogenesis. Inflammasomes, which are vital cytosolic multiprotein complexes assembled in response to infections and stress, are crucial to activating inflammatory processes in macrophages. Chronic inflammation, characterized by prolonged tissue injury and repair cycles, can significantly damage tissues, thereby increasing the risk of AIDs. Inhibiting inflammasomes, particularly in autoinflammatory disorders, has garnered significant interest, with pharmaceutical advancements targeting cytokines and inflammasomes showing promise in AID management. Full article
(This article belongs to the Special Issue Advances in Understanding Molecular Basis of Inflammatory Diseases)
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13 pages, 6212 KiB  
Article
AESIS-1, a Rheumatoid Arthritis Therapeutic Peptide, Accelerates Wound Healing by Promoting Fibroblast Migration in a CXCR2-Dependent Manner
by Seung Beom Park, Yoolhee Yang, Sa Ik Bang, Tae Sung Kim and Daeho Cho
Int. J. Mol. Sci. 2024, 25(7), 3937; https://doi.org/10.3390/ijms25073937 - 1 Apr 2024
Cited by 4 | Viewed by 3399
Abstract
In patients with autoimmune disorders such as rheumatoid arthritis (RA), delayed wound healing is often observed. Timely and effective wound healing is a crucial determinant of a patient’s quality of life, and novel materials for skin wound repair, such as bioactive peptides, are [...] Read more.
In patients with autoimmune disorders such as rheumatoid arthritis (RA), delayed wound healing is often observed. Timely and effective wound healing is a crucial determinant of a patient’s quality of life, and novel materials for skin wound repair, such as bioactive peptides, are continuously being studied and developed. One such bioactive peptide, AESIS-1, has been studied for its well-established anti-rheumatoid arthritis properties. In this study, we attempted to use the anti-RA material AESIS-1 as a therapeutic wound-healing agent based on disease-modifying antirheumatic drugs (DMARDs), which can help restore prompt wound healing. The efficacy of AESIS-1 in wound healing was assessed using a full-thickness excision model in diabetic mice; this is a well-established model for studying chronic wound repair. Initial observations revealed that mice treated with AESIS-1 exhibited significantly advanced wound repair compared with the control group. In vitro studies revealed that AESIS-1 increased the migration activity of human dermal fibroblasts (HDFs) without affecting proliferative activity. Moreover, increased HDF cell migration is mediated by upregulating chemokine receptor expression, such as that of CXC chemokine receptor 2 (CXCR2). The upregulation of CXCR2 through AESIS-1 treatment enhanced the chemotactic reactivity to CXCR2 ligands, including CXC motif ligand 8 (CXCL8). AESIS-1 directly activates the ERK and p38 mitogen-activated protein kinase (MAPK) signaling cascades, which regulate the migration and expression of CXCR2 in fibroblasts. Our results suggest that the AESIS-1 peptide is a strong wound-healing substance that increases the movement of fibroblasts and the expression of CXCR2 by turning on the ERK and p38 MAPK signaling cascades. Full article
(This article belongs to the Special Issue Recent Approaches for Wound Treatment—2nd Edition)
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20 pages, 3078 KiB  
Review
The Use of Small-Molecule Compounds for Cell Adhesion and Migration in Regenerative Medicine
by Juan Mitchell and Kevin W.-H. Lo
Biomedicines 2023, 11(9), 2507; https://doi.org/10.3390/biomedicines11092507 - 11 Sep 2023
Cited by 5 | Viewed by 2928
Abstract
Cell adhesion is essential for cell survival, communication, and regulation, and it is of fundamental importance in the development and maintenance of tissues. Cell adhesion has been widely explored due to its many important roles in the fields of tissue regenerative engineering and [...] Read more.
Cell adhesion is essential for cell survival, communication, and regulation, and it is of fundamental importance in the development and maintenance of tissues. Cell adhesion has been widely explored due to its many important roles in the fields of tissue regenerative engineering and cell biology. This is because the mechanical interactions between a cell and its extracellular matrix (ECM) can influence and control cell behavior and function. Currently, biomaterials for regenerative medicine have been heavily investigated as substrates for promoting a cells’ adhesive properties and subsequent proliferation, tissue differentiation, and maturation. Specifically, the manipulation of biomaterial surfaces using ECM coatings such as fibronectin extracted from animal-derived ECM have contributed significantly to tissue regenerative engineering as well as basic cell biology research. Additionally, synthetic and natural bioadhesive agents with pronounced abilities to enhance adhesion in numerous biological components and molecules have also been assessed in the field of tissue regeneration. Research into the use of facilitative bioadhesives has aimed to further optimize the biocompatibility, biodegradability, toxicity levels, and crosslinking duration of bioadhesive materials for improved targeted delivery and tissue repair. However, the restrictive drawbacks of some of these bioadhesive and animal-derived materials include the potential risk of disease transmission, immunogenicity, poor reproducibility, impurities, and instability. Therefore, it is necessary for alternative strategies to be sought out to improve the quality of cell adhesion to biomaterials. One promising strategy involves the use of cell-adhesive small molecules. Small molecules are relatively inexpensive, stable, and low-molecular-weight (<1000 Da) compounds with great potential to serve as efficient alternatives to conventional bioadhesives, ECM proteins, and other derived peptides. Over the past few years, a number of cell adhesive small molecules with the potential for tissue regeneration have been reported. In this review, we discuss the current progress using cell adhesive small molecules to regulate tissue regeneration. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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18 pages, 1229 KiB  
Review
Therapeutic Targeting of DNA Replication Stress in Cancer
by Long Gu, Robert J. Hickey and Linda H. Malkas
Genes 2023, 14(7), 1346; https://doi.org/10.3390/genes14071346 - 26 Jun 2023
Cited by 20 | Viewed by 7868
Abstract
This article reviews the currently used therapeutic strategies to target DNA replication stress for cancer treatment in the clinic, highlighting their effectiveness and limitations due to toxicity and drug resistance. Cancer cells experience enhanced spontaneous DNA damage due to compromised DNA replication machinery, [...] Read more.
This article reviews the currently used therapeutic strategies to target DNA replication stress for cancer treatment in the clinic, highlighting their effectiveness and limitations due to toxicity and drug resistance. Cancer cells experience enhanced spontaneous DNA damage due to compromised DNA replication machinery, elevated levels of reactive oxygen species, loss of tumor suppressor genes, and/or constitutive activation of oncogenes. Consequently, these cells are addicted to DNA damage response signaling pathways and repair machinery to maintain genome stability and support survival and proliferation. Chemotherapeutic drugs exploit this genetic instability by inducing additional DNA damage to overwhelm the repair system in cancer cells. However, the clinical use of DNA-damaging agents is limited by their toxicity and drug resistance often arises. To address these issues, the article discusses a potential strategy to target the cancer-associated isoform of proliferating cell nuclear antigen (caPCNA), which plays a central role in the DNA replication and damage response network. Small molecule and peptide agents that specifically target caPCNA can selectively target cancer cells without significant toxicity to normal cells or experimental animals. Full article
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14 pages, 2512 KiB  
Article
Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing
by Floriana Cappiello, Sudhir Verma, Xiao Lin, Isabel Y. Moreno, Bruno Casciaro, Debarun Dutta, Alison M. McDermott, Mark Willcox, Vivien J. Coulson-Thomas and Maria Luisa Mangoni
Biomolecules 2023, 13(7), 1028; https://doi.org/10.3390/biom13071028 - 23 Jun 2023
Cited by 7 | Viewed by 3588
Abstract
The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can [...] Read more.
The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range. Full article
(This article belongs to the Topic Natural Products and Drug Discovery)
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32 pages, 2197 KiB  
Review
Antimicrobial Peptides: Challenging Journey to the Pharmaceutical, Biomedical, and Cosmeceutical Use
by Anna Mazurkiewicz-Pisarek, Joanna Baran and Tomasz Ciach
Int. J. Mol. Sci. 2023, 24(10), 9031; https://doi.org/10.3390/ijms24109031 - 20 May 2023
Cited by 66 | Viewed by 8586
Abstract
Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. Here we discuss AMPs, which may become a promising substitute or adjuvant in pharmaceutical, biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and [...] Read more.
Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. Here we discuss AMPs, which may become a promising substitute or adjuvant in pharmaceutical, biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and antifungal drugs and as promising antiviral and anticancer agents. AMPs exhibit many properties, and some of these have attracted the attention of the cosmetic industry. AMPs are being developed as novel antibiotics to combat multidrug-resistant pathogens and as potential treatments for various diseases, including cancer, inflammatory disorders, and viral infections. In biomedicine, AMPs are being developed as wound-healing agents because they promote cell growth and tissue repair. The immunomodulatory effects of AMPs could be helpful in the treatment of autoimmune diseases. In the cosmeceutical industry, AMPs are being investigated as potential ingredients in skincare products due to their antioxidant properties (anti-ageing effects) and antibacterial activity, which allows the killing of bacteria that contribute to acne and other skin conditions. The promising benefits of AMPs make them a thrilling area of research, and studies are underway to overcome obstacles and fully harness their therapeutic potential. This review presents the structure, mechanisms of action, possible applications, production methods, and market for AMPs. Full article
(This article belongs to the Special Issue Peptide Antimicrobial Agents 3.0)
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20 pages, 3995 KiB  
Review
Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol
by Jose Manuel Quesada-Gomez, José Lopez-Miranda, Marta Entrenas-Castillo, Antonio Casado-Díaz, Xavier Nogues y Solans, José Luis Mansur and Roger Bouillon
Nutrients 2022, 14(13), 2716; https://doi.org/10.3390/nu14132716 - 29 Jun 2022
Cited by 28 | Viewed by 6862
Abstract
The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there [...] Read more.
The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin–angiotensin–bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents. Full article
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15 pages, 4601 KiB  
Article
BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents
by Zida Zhu, Taisuke Kitano, Masami Morimatsu, Arisa Tanaka, Ryo Morioka, Xianghui Lin, Koichi Orino and Yasunaga Yoshikawa
Int. J. Mol. Sci. 2022, 23(7), 4060; https://doi.org/10.3390/ijms23074060 - 6 Apr 2022
Cited by 1 | Viewed by 3359
Abstract
Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand crosslinking agents or X-ray irradiation, which induces DNA double-strand breaks. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51 oligomer-containing nucleofilaments. In [...] Read more.
Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand crosslinking agents or X-ray irradiation, which induces DNA double-strand breaks. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51 oligomer-containing nucleofilaments. In this study, we investigated CTRBD expression in cells exposed to X-ray irradiation and mitomycin C treatment. Surprisingly, BRCA2 CTRBD expression in HeLa cells increased their resistance to X-ray irradiation and mitomycin C. Under endogenous BRCA2 depletion using shRNA, the sensitivities of the BRCA2-depleted cells with and without the CTRBD did not significantly differ. Thus, the resistance to X-ray irradiation conferred by an exogenous CTRBD required endogenous BRCA2 expression. BRCA2 CTRBD-expressing cells demonstrated effective RAD51 foci formation and increased homologous recombination efficiency, but not nonhomologous end-joining efficiency. To the best of our knowledge, our study is the first to report the ability of the BRCA2 functional domain to confer resistance to X-ray irradiation and mitomycin C treatment by increased homologous recombination efficiency. Thus, this peptide may be useful for protecting cells against X-ray irradiation or chemotherapeutic agents. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Biology and Medicine)
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