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81 pages, 6368 KB  
Review
A Comprehensive Review on the Valorization of Bioactives from Marine Animal By-Products for Health-Promoting, Biofunctional Cosmetics
by Sofia Neonilli A. Papadopoulou, Theodora Adamantidi, Dimitrios Kranas, Paschalis Cholidis, Chryssa Anastasiadou and Alexandros Tsoupras
Mar. Drugs 2025, 23(8), 299; https://doi.org/10.3390/md23080299 - 26 Jul 2025
Viewed by 959
Abstract
In recent decades, there has been a marked surge in the development of marine-by-product-derived ingredients for cosmetic applications, driven by the increasing demand for natural, sustainable, and high-performance formulations. Marine animal by-products, particularly those from fish, crustaceans, and mollusks, represent an abundant yet [...] Read more.
In recent decades, there has been a marked surge in the development of marine-by-product-derived ingredients for cosmetic applications, driven by the increasing demand for natural, sustainable, and high-performance formulations. Marine animal by-products, particularly those from fish, crustaceans, and mollusks, represent an abundant yet underutilized source of bioactive compounds with notable potential in cosmeceutical innovation. Generated as waste from the fishery and seafood-processing industries, these materials are rich in valuable bioactives, such as chitosan, collagen, peptides, amino acids, fatty acids, polar lipids, lipid-soluble vitamins, carotenoids, pigments, phenolics, and mineral-based substrates like hydroxyapatite. Marine by-product bioactives can be isolated via several extraction methods, and most importantly, green ones. These compounds exhibit a broad spectrum of skin-health-promoting effects, including antioxidant, anti-aging, anti-inflammatory, antitumor, anti-wrinkle, anti-hyperpigmentation, and wound-healing properties. Moreover, applications extend beyond skincare to include hair, nail, and oral care. The present review provides a comprehensive analysis of bioactives obtained from marine mollusks, crustaceans, and fish by-products, emphasizing modern extraction technologies with a focus on green and sustainable approaches. It further explores their mechanisms of action and documented efficacy in cosmetic formulations. Finally, the review outlines current limitations and offers future perspectives for the industrial valorization of marine by-products in functional and environmentally-conscious cosmetic development. Full article
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17 pages, 1430 KB  
Article
Circular Animal Protein Hydrolysates: A Comparative Approach of Functional Properties
by Marta Monteiro, Luciano Rodrigues-dos-Santos, Andreia Filipa-Silva, Diana A. Marques, Manuela Pintado, André Almeida and Luisa M. P. Valente
Antioxidants 2025, 14(7), 782; https://doi.org/10.3390/antiox14070782 - 25 Jun 2025
Viewed by 854
Abstract
The growing demand for nutraceuticals has driven interest in upcycling low-value proteins from processed animal by-products and insect larvae into functional protein hydrolysates. This study evaluated five such hydrolysates in comparison to a high-value commercial reference (CPSP90), assessing the proximate composition, amino acid [...] Read more.
The growing demand for nutraceuticals has driven interest in upcycling low-value proteins from processed animal by-products and insect larvae into functional protein hydrolysates. This study evaluated five such hydrolysates in comparison to a high-value commercial reference (CPSP90), assessing the proximate composition, amino acid profile, molecular weight distribution, antioxidant activity, and bacterial growth dynamics. Results revealed a wide variability in the composition and bioactivity, driven by the raw material and processing conditions. All hydrolysates displayed a medium to high crude protein content (55.1–89.5% DM), with SHARK being the most protein-rich. SHARK and SWINE hydrolysates were particularly rich in collagenic amino acids, while FISH and CPSP90 contained higher levels of essential amino acids. FISH and INSECT demonstrated the strongest antioxidant activity, with INSECT also showing the highest protein solubility. INSECT and SWINE further displayed mild, selective antibacterial effects, indicating a potential for disease mitigation. Conversely, SHARK and FISH supported opportunistic bacteria growth, suggesting a potential use as nitrogen sources in microbial media. These findings highlight the nutritional and functional versatility of animal-derived protein hydrolysates and support their integration into sustainable feed strategies within a circular bioeconomy. Full article
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23 pages, 3484 KB  
Article
In Silico Design, Optimization, and Evaluation of a Multi-Epitope Vaccine Targeting the Clostridium perfringens Collagen Adhesin Protein
by Dhiraj Chundru, Shailes Bhattrai, Madhusudan Timilsina, Hyun Lillehoj, Zhifeng Sun, Mostafa Ghanem and Charles Li
Microorganisms 2025, 13(5), 1147; https://doi.org/10.3390/microorganisms13051147 - 16 May 2025
Viewed by 1005
Abstract
Necrotic enteritis (NE), caused by pathogenic Clostridium perfringens, poses a significant threat to global poultry health, with estimated annual losses exceeding USD 6 billion. The rising incidence of NE has been associated with the reduced use of antibiotic growth promoters, underscoring the [...] Read more.
Necrotic enteritis (NE), caused by pathogenic Clostridium perfringens, poses a significant threat to global poultry health, with estimated annual losses exceeding USD 6 billion. The rising incidence of NE has been associated with the reduced use of antibiotic growth promoters, underscoring the urgent need for alternative control measures such as vaccination. Collagen adhesin protein (CNA), a key virulence factor in NE pathogenesis, represents a promising vaccine target. The US Food and Drug Administration has begun phasing out animal testing requirements for biologics and monoclonal antibody drugs. In this study, a computational multi-epitope vaccine (MEV) targeting CNA was designed by integrating predicted Cluster of Differentiation (CD)4+ helper T lymphocyte (Th), CD8+ cytotoxic T lymphocyte (CTL), and B-cell epitopes. Bioinformatics tools were used to identify immunogenic, antigenic, and non-allergenic epitopes assembled into a 115-amino-acid peptide vaccine construct. The candidate demonstrated strong stability and solubility. In silico immune simulation predicted robust immune responses, including elevated IgG and IgM antibody levels, plasma cell proliferation, Th memory formation, and CTL activation, comparable to responses elicited by a full-length CNA. These findings support the potential of the designed peptide as one of the multiple effective NE vaccine components, offering a promising alternative to antibiotic-based approaches in poultry disease management. Full article
(This article belongs to the Special Issue Poultry Pathogens and Poultry Diseases, 2nd Edition)
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23 pages, 14210 KB  
Article
In Vivo Evaluation of the Anti-Skin-Ageing Bioactivity of a Recombinant Dual Humanised Collagen and Poly-L-Lactic Acid
by Mingjie Tong, Xin Zhou, Jiongni Zhong, Dengjian Qu, Wei Chen, Chun Chen, Yiting Wang, Yaoping Liu, Shaochuan Li, Yuan Xiao, Ning Wang, Chaowan Guo, Qiuling Xie and Sheng Xiong
Bioengineering 2025, 12(5), 510; https://doi.org/10.3390/bioengineering12050510 - 12 May 2025
Viewed by 1114
Abstract
This study introduces a novel recombinant humanised collagen (DuCol) developed through codon optimisation and prokaryotic soluble expression, exhibiting exceptional biocompatibility and bioactivity. Structural integrity was confirmed via RP-HPLC, SEM, and CD spectroscopy. In vitro evaluations revealed DuCol’s dose-dependent enhancement of NIH-3T3 fibroblast proliferation, [...] Read more.
This study introduces a novel recombinant humanised collagen (DuCol) developed through codon optimisation and prokaryotic soluble expression, exhibiting exceptional biocompatibility and bioactivity. Structural integrity was confirmed via RP-HPLC, SEM, and CD spectroscopy. In vitro evaluations revealed DuCol’s dose-dependent enhancement of NIH-3T3 fibroblast proliferation, adhesion, and migration. In a D-galactose-induced ageing rat model, subcutaneous implantation of DuCol showcased time-dependent anti-ageing effects. Early-stage intervention (30 days post-injection) markedly upregulated COL1A1 expression through the TGF-β/Smad3 pathway activation, outperforming poly-l-lactic acid (PLLA) in collagen deposition. Histological analysis revealed 23.4% greater dermal thickness in DuCol-treated groups compared to PLLA at 90 days. While PLLA exhibited sustained collagen stimulation beyond 90 days, DuCol exhibited superior early-phase efficacy (p < 0.001) with comparable safety profiles (no inflammatory response observed through 180-day monitoring). The combinatorial PLLA/DuCol (P&C) formulation synergistically enhanced dermal regeneration, achieving a 31.7% thicker collagen matrix than monotherapy groups. These results underscore the potential of DuCol as a novel implantable filler material for skin repair and regeneration. Full article
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38 pages, 10556 KB  
Article
Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer
by Sammar Fathy Elhabal, Ahmed Mohsen Faheem, Sandra Hababeh, Jakline Nelson, Nahla A. Elzohairy, Yasmine F. Ibrahim, Tassneim M. Ewedah, Ibrahim S. Mousa, Khaled M. Allam and Ahmed Mohsen Elsaid Hamdan
Pharmaceutics 2025, 17(5), 611; https://doi.org/10.3390/pharmaceutics17050611 - 5 May 2025
Cited by 3 | Viewed by 1172
Abstract
Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate [...] Read more.
Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate solid lipid nanoparticles (SLNs) that contained Althaea officinalis (marshmallow) (M.) extract with clove oil (CO.), subsequently integrated into a collagen sponge for enhancing stability, solubility, sustained release, antimicrobial efficacy, and healing power when targeting diabetic oral ulcers. Methods: A factorial design of 34 trials was established to evaluate the influence of lipid concentration (A), SAA concentration (B), lipid type (C), and SAA type (D). The optimized M-CO-SLNs was selected using Design Expert®, the based Poly dispersibility index (Y2), zeta potential (MV) (Y3), and encapsulation efficiency (%) (Y4). The optimized SLNs were integrated into a collagen sponge matrix and tested for their antibacterial and antifungal efficacy against Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively. Moreover, they were tested for their wound healing power in a diabetic mouth ulcer model. Results: The optimized formula (Run 16: 5% lipid concentration, 4% SAA concentration, capric acid) demonstrated P.S (110 ± 0.76 nm), ZP (−24 ± 0.32 mV), PDI (0.18 ± 0.05), and EE% (90 ± 0.65%.). The optimized M-CO-SLNs formula was incorporated into a cross-linked collagen sponge and showed superior antimicrobial efficacy, an increased swelling ratio, and was effective in an in vivo oral ulcer study, as evidenced by ELISA biomarkers, gene expression analysis, and histological analysis. Conclusions: M-CO-SLNs embedded in collagen sponges is a promising therapeutic formula for clinical application against diabetic mouth ulcers. Full article
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22 pages, 9280 KB  
Article
Properties of Emulsion Co-Precipitated Collagen/Bambara Groundnut Protein-Based Film as Influenced by Basil Essential Oil and Soy Lecithin
by Md. Shihabul Awal, Soottawat Benjakul, Thummanoon Prodpran and Krisana Nilsuwan
Polymers 2025, 17(9), 1139; https://doi.org/10.3390/polym17091139 - 22 Apr 2025
Viewed by 1095
Abstract
Protein-based films have gained attention due to their potential as biodegradable packaging. This study investigated the properties and characteristics of film-forming emulsions (FFEs) and their films based on co-precipitated protein (CPP) from Bambara groundnut protein isolate (BGPI) and acid-soluble collagen (ASC) emulsified with [...] Read more.
Protein-based films have gained attention due to their potential as biodegradable packaging. This study investigated the properties and characteristics of film-forming emulsions (FFEs) and their films based on co-precipitated protein (CPP) from Bambara groundnut protein isolate (BGPI) and acid-soluble collagen (ASC) emulsified with different levels of basil essential oil (BE) (50%, 75% and 100%) and soy lecithin (SL) (25% and 50%). The oil droplet size, stability, and distribution of FFEs were characterized. Larger oil droplet sizes, a higher flocculation factor, and a higher coalescence index were observed for FFEs emulsified with higher levels of BE and SL. All FFEs had uniform oil distribution. Films from different FFEs were formed and analyzed. Films containing BE and SL had higher thickness, elongation at break, b*-value, water vapor and UV-light barrier properties, but a lower tensile strength than the control film. Emulsion films exhibited smooth surface and rough cross-section and were heat-sealable. FTIR spectra indicated lower protein interactions in the emulsion film containing higher levels of BE and SL. The film containing 100% BE had the highest antioxidant activities, regardless of the SL level used. The emulsification of BE and SL at various levels thus influenced the properties and characteristics of the FFE and emulsion film. Full article
(This article belongs to the Section Biobased and Biodegradable Polymers)
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13 pages, 1406 KB  
Review
A Review of Classical and Rising Approaches the Extraction and Utilization of Marine Collagen
by Cesia Deyanira Gutierrez-Canul, Luis Alfonso Can-Herrera, Emmanuel de Jesús Ramírez-Rivera, Witoon Prinyawiwatkul, Enrique Sauri-Duch, Victor Manuel Moo-Huchin and Emanuel Hernández-Núñez
BioTech 2025, 14(2), 26; https://doi.org/10.3390/biotech14020026 - 3 Apr 2025
Cited by 2 | Viewed by 1624
Abstract
This comprehensive review explores the extraction and utilization of marine collagen, a sustainable alternative to traditional mammalian sources. The review covers conventional extraction methods like acid and pepsin solubilization, highlighting their limitations and contributing to the search for improved efficiency and sustainability. It [...] Read more.
This comprehensive review explores the extraction and utilization of marine collagen, a sustainable alternative to traditional mammalian sources. The review covers conventional extraction methods like acid and pepsin solubilization, highlighting their limitations and contributing to the search for improved efficiency and sustainability. It also delves into innovative extraction technologies, such as ultrasound-assisted extraction, deep eutectic solvents, and supercritical carbon dioxide, showing their potential to revolutionize the field. The significance of collagen hydrolysis in generating bioactive peptides with diverse functionalities is also discussed, emphasizing their potential applications in various sectors. By providing an analysis of marine collagen extraction and its implications, this review presents a perspective for leveraging this valuable bioresource, promoting a circular economy, and satisfying the increasing demand for high-quality collagen in diverse industries. Full article
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16 pages, 2496 KB  
Article
Properties and Characteristics of Film from Salmon Skin Acid-Soluble Collagen Solution as Influenced by Ultrasonication Process
by Krisana Nilsuwan, Sujinun Thongnoi, Thummanoon Prodpran and Soottawat Benjakul
Foods 2025, 14(7), 1088; https://doi.org/10.3390/foods14071088 - 21 Mar 2025
Cited by 1 | Viewed by 636
Abstract
Salmon skin is a byproduct from the fish processing industry that can be used as a potential source of collagen. Due to the presence of other constituents, pretreatment of the skin is required prior to the preparation of the acid-soluble collagen (ASC) solution [...] Read more.
Salmon skin is a byproduct from the fish processing industry that can be used as a potential source of collagen. Due to the presence of other constituents, pretreatment of the skin is required prior to the preparation of the acid-soluble collagen (ASC) solution and film. This study aimed to investigate the effects of ultrasonication amplitudes (50% and 70%) and times (5, 10, and 15 min) on the properties and characteristics of ASC solutions and films. The ASC solutions had higher elastic behavior when ultrasonication at a lower amplitude and a shorter time was used. Films from solutions ultrasonicated at 50% amplitude had a higher thickness, tensile strength, elongation at break, and water vapor barrier property than films from solutions ultrasonicated at 70% amplitude, regardless of the ultrasonication time used. A longer ultrasonication time decreased the L* value but increased the transparency value. The FTIR spectra indicated that structural modifications were affected by the ultrasonication conditions used. The SEM images showed a continuous surface for all the films. Higher amplitudes and longer times reduced the thermal stability and crystallinity, respectively, as determined by differential scanning calorimetry and thermogravimetric analysis as well as X-ray diffraction. Therefore, ultrasonication at 50% amplitude for 10 min was suitable for producing films with satisfactory mechanical and water vapor barrier properties. Full article
(This article belongs to the Section Foods of Marine Origin)
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20 pages, 3514 KB  
Article
Enhancing Thin Film Properties of Chitosan–Collagen Biocomposites Through Potassium Silicate and Tannic Acid Integration
by Beata Kaczmarek-Szczepańska, Ugo D’Amora, Lidia Zasada, Marta Michalska-Sionkowska, Oliwia Miłek, Krzysztof Łukowicz and Anna Maria Osyczka
Polymers 2025, 17(5), 608; https://doi.org/10.3390/polym17050608 - 25 Feb 2025
Cited by 3 | Viewed by 1249
Abstract
Chitosan and collagen are natural polymers widely used in biomaterials science; however, their inherent low stability and solubility present several challenges to obtain formulations suitable for potential clinical applications. In this study, tannic acid (TA) was employed as a cross-linker to improve the [...] Read more.
Chitosan and collagen are natural polymers widely used in biomaterials science; however, their inherent low stability and solubility present several challenges to obtain formulations suitable for potential clinical applications. In this study, tannic acid (TA) was employed as a cross-linker to improve the properties of thin films made from chitosan and collagen. In addition, potassium silicate (PS) was added as an inorganic filler, to produce innovative biocomposite films. The impact of TA and PS on physicochemical (i.e., material homogeneity, surface free energy, degradation, and stability roughness of surface), antioxidant, hemocompatibility, as well as cellular responses was evaluated. The results demonstrated that the incorporation of TA significantly enhanced the physicochemical properties of the chitosan/collagen-based films. The addition of 5% PS resulted in an increase in surface free energy and a decrease in roughness parameters. Furthermore, both surface free energy and cellular responses improved with the increased TA concentration in the biocomposite firms. Meanwhile, the hemolysis rate remained below 5%, indicating the potential suitability of these materials for medical applications, such as coatings or scaffolds for bone or skin wound healing. Full article
(This article belongs to the Special Issue Polymer Thin Films and Their Applications)
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16 pages, 1017 KB  
Article
Alpha-Lipoic Acid Treatment Reduces the Levels of Advanced End Glycation Products in Type 2 Diabetes Patients with Neuropathy
by Sára Csiha, Marcell Hernyák, Ágnes Molnár, Hajnalka Lőrincz, Mónika Katkó, György Paragh, Miklós Bodor, Mariann Harangi, Ferenc Sztanek and Eszter Berta
Biomedicines 2025, 13(2), 438; https://doi.org/10.3390/biomedicines13020438 - 11 Feb 2025
Cited by 3 | Viewed by 4939
Abstract
Background/Objectives: Type 2 diabetes mellitus (T2DM) and its macro- and microvascular complications are major health concerns with multiple factors, like advanced end glycation products (AGEs), in the background. AGEs induce long-lasting functional modification of the proteins and collagen in the vascular wall and [...] Read more.
Background/Objectives: Type 2 diabetes mellitus (T2DM) and its macro- and microvascular complications are major health concerns with multiple factors, like advanced end glycation products (AGEs), in the background. AGEs induce long-lasting functional modification of the proteins and collagen in the vascular wall and nerve tissue. We investigated the effect of alpha-lipoic acid (ALA) treatment on AGEs, soluble AGE receptor (sRAGE), the AGE/sRAGE ratio, and the parameters of endothelial dysfunction and their correlations. Methods: In our 6-month intervention study, 54 T2DM patients with neuropathy treated according to the actual therapeutic guidelines with unchanged oral antidiabetic drugs were included and treated by daily oral administration of 600 mg ALA. A total of 24 gender and age-matched T2DM patients without neuropathy served as controls. Results: In our work, we first demonstrated the attenuating effect of alpha lipoic acid therapy on AGEs in humans (11.89 (9.44–12.88) to 10.95 (9.81–12.82) AU/μg (p = 0.017)). sRAGE levels or the AGEs/sRAGE ratio were not affected by ALA treatment or by the presence of neuropathy. We found a correlation between the changes of AGEs and the improvement of current perception threshold and progranulin levels, and an inverse correlation with the change of asymmetric dimethylarginine. Conclusions: According to our results, ALA decreases AGEs, which may contribute to the clinically well-known beneficial effect in diabetic neuropathy and improvement of endothelial function. Full article
(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)
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15 pages, 3821 KB  
Article
Isolation and Characterisation of Acid Soluble Collagens and Pepsin Soluble Collagens from Eel (Anguilla japonica Temminck et Schlegel) Skin and Bone
by Ningning Zhang, Shaoli Guo, Yuting Zheng and Weili Li
Foods 2025, 14(3), 502; https://doi.org/10.3390/foods14030502 - 5 Feb 2025
Viewed by 1488
Abstract
Eel (Anguilla japonica) is an important and valuable food fish in East Asia and its by-products have been reported to include bioactive and profitable components. This study aimed to extract, characterise, and compare the structure and properties of acid-soluble collagens (ASCs) [...] Read more.
Eel (Anguilla japonica) is an important and valuable food fish in East Asia and its by-products have been reported to include bioactive and profitable components. This study aimed to extract, characterise, and compare the structure and properties of acid-soluble collagens (ASCs) and pepsin-soluble collagens (PSCs) from the skin and bone of eel (Anguilla japonica), providing insights into their composition, structure, and properties for various applications. The yields of ASC-S (from skin), PSC-S (from skin), ASC-B (from bone), and PSC-B (from bone) were 12.16%, 15.54%, 0.79%, and 1.34% on a dry weight basis, respectively. Glycine, the dominant amino acid, accounted for 16.66% to 22.67% of total amino acids in all samples. SDS-PAGE and FTIR analyses showed the typical triple-helical structure of type I collagen with slight variations in molecular order in extract and intermolecular cross-linking between skin and bone collagens. The denaturation temperature (Tmax1) measured by differential scanning calorimetry (DSC) is 81.39 °C and 74.34 °C, respectively, for ASC-B and ASC-S. Bone collagen has higher thermal resistance than skin collagen. Surface morphology imaged using a scanning electron microscope (SEM) showed that the bone collagen had a denser network structure, whilst the skin collagen was more fibrous and porous. The findings suggest that eel-derived collagens from skin and bone can serve as potential alternatives in the food, cosmetic, and healthcare industries. Full article
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13 pages, 4128 KB  
Article
Pharmacokinetic and Pharmacodynamic Study of Folic Acid-Modified Chitosan–Stearic Acid Nanomicelles Loaded with Tetrandrine for Rheumatoid Arthritis
by Shuai Ma, Fei Xue, Lan Yang, Long Chen, Pei Liu, Jinhua Chang and Ruxing Wang
Pharmaceutics 2025, 17(2), 169; https://doi.org/10.3390/pharmaceutics17020169 - 27 Jan 2025
Viewed by 1389
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, and it is currently incurable. Tetrandrine (TET) has an obvious curative effect with therapeutic efficacy on RA, but its use is limited due to its poor water-solubility and bioavailability. Therefore, TET-loaded nanomicelles modified with [...] Read more.
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, and it is currently incurable. Tetrandrine (TET) has an obvious curative effect with therapeutic efficacy on RA, but its use is limited due to its poor water-solubility and bioavailability. Therefore, TET-loaded nanomicelles modified with chitosan, stearic acid, and folic acid (FCST) was prepared in the study, and the pharmacokinetics and pharmacodynamics were studied. Methods: The plasma concentrations of FCST and TET were measured by the PLC-MS/MS method at different times, and the pharmacokinetic parameters were calculated. A collagen-induced arthritis (CIA) model was established with rats. On the 16th day after the first immunization, 50 rats were randomized into five groups with 10 rats in each group according to the arthritis score. The drugs were administered by intraperitoneal injection for 30 days. The swelling degree and joint score of the rats were tested during each administration. In addition, the pro-inflammatory factors IL-1β, IL-6, IL-17, and TNF-α in the serum of the rats were tested by an ELISA kit, and their joints were examined by histopathology. Results: Pharmacokinetic studies showed that the AUC0–72h of FCST was 1.93 times that of TET. FCST demonstrated higher bioavailability compared to TET (p < 0.05). Pharmacodynamic studies demonstrated that FCST had significant anti-inflammatory effects, and its anti-inflammatory activity was stronger compared to the same dose of TET, as evidenced by measuring toe thickness and observing toe appearance. It significantly reduced the expression of IL-1, IL-6, IL-17, and TNF-α in rats with rheumatoid arthritis (p < 0.05). Conclusions: FCST can significantly improve bioavailability and has a significant therapeutic effect on rheumatoid arthritis. Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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15 pages, 2401 KB  
Article
N-Oxalylglycine-Conjugated Hyaluronic Acid as a Macromolecular Prodrug for Therapeutic Angiogenesis
by Andrew H. DeMaria, Jeoung Soo Lee and Ken Webb
Gels 2025, 11(1), 27; https://doi.org/10.3390/gels11010027 - 2 Jan 2025
Cited by 1 | Viewed by 849
Abstract
Hypoxia-inducible factor-1α (HIF-1α) initiates the cellular response to low oxygen levels, making it an attractive target for stimulating therapeutic angiogenesis. Several small molecules have been identified that stabilize HIF-1α and activate the angiogenic signaling pathway. However, achieving therapeutic doses of bioactive small molecules [...] Read more.
Hypoxia-inducible factor-1α (HIF-1α) initiates the cellular response to low oxygen levels, making it an attractive target for stimulating therapeutic angiogenesis. Several small molecules have been identified that stabilize HIF-1α and activate the angiogenic signaling pathway. However, achieving therapeutic doses of bioactive small molecules in target tissues remains challenging. In this paper, we report the synthesis and characterization of a new macromolecular prodrug composed of the pro-angiogenic small molecule N-oxalylglycine conjugated to hyaluronic acid (HA-NOG). NOG was conjugated to HA by esterification, and release was significantly increased in the presence of degradative enzymes, esterase and hyaluronidase, compared to physiological buffer, confirming that the release of NOG is primarily enzymatically driven. Normal human dermal fibroblasts (NHDFs) cultured with HA-NOG exhibited HIF-1α accumulation in the cell nucleus and dose-dependent increases in mRNA expression levels of three direct HIF transcriptional targets. Conditioned medium from these cells stimulated endothelial cell tubulogenesis. As an initial evaluation of safety and possible side effects, HA-NOG was found not to significantly affect NHDF metabolic activity, proliferation, or collagen deposition. These studies demonstrate that HA-NOG releases NOG in response to cellular enzymatic activity, activating the HIF signaling pathway and culminating in the secretion of soluble factors that activate endothelial cells without adversely affecting other cellular metabolic pathways. Full article
(This article belongs to the Special Issue Functional Gels Applied in Tissue Engineering)
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Proceeding Paper
Unlocking the Potential of Fishery Waste: Acid-Soluble Ultrasound Extraction of Marine Collagen from Sardine Fish Scales
by Afaf Moufaddel, Khalid Bougrin, Hanae El Monfalouti and Badr Eddine Kartah
Chem. Proc. 2024, 16(1), 115; https://doi.org/10.3390/ecsoc-28-20194 - 14 Nov 2024
Viewed by 387
Abstract
Globally, fish consumption generates significant waste from fish markets and processing industries, including fish skin, scales, and bones. If not appropriately managed, this fishery waste can lead to environmental pollution. Collagen, the most abundant protein in animal bodies, has diverse medical, biomedical, and [...] Read more.
Globally, fish consumption generates significant waste from fish markets and processing industries, including fish skin, scales, and bones. If not appropriately managed, this fishery waste can lead to environmental pollution. Collagen, the most abundant protein in animal bodies, has diverse medical, biomedical, and pharmaceutical applications, but its high cost has constrained its usage. Collagen derived from marine sources, particularly from the by-products of fish processing, is seen as an alternative to collagens from land animals. There has been growing interest in utilizing fish scales as a cost-effective source of this valuable collagen-rich protein. Repurposing fish scales could alleviate environmental pressure and create additional commercial value. In a recent study, collagen was isolated from the scales of Moroccan Sardina pilchardus, a fish species renowned for its high collagen content. This marine collagen type I features a triple alpha-helical structure comprising one α2 chain and two α1 chains. The collagen extraction was accomplished using the acid-soluble collagen (ASC) method combined with an ultrasound technique after pretreating the fish scales, involving a demineralization step to remove a high amount of minerals. The ASC extracted from the sardine scales exhibited high solubility in the highly acidic pH range (pH 2). Various physicochemical techniques, such as FTIR, DRX, and SEM, confirmed the isolated protein as collagen. Hence, sardine scales could serve as an alternative source of collagen, and the characteristics of the collagens were minimally affected by the extraction process employed. Full article
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28 pages, 13740 KB  
Article
A Novel P-III Metalloproteinase from Bothrops barnetti Venom Degrades Extracellular Matrix Proteins, Inhibits Platelet Aggregation, and Disrupts Endothelial Cell Adhesion via α5β1 Integrin Receptors to Arginine–Glycine–Aspartic Acid (RGD)-Containing Molecules
by Pedro Henrique de Caires Schluga, Debora Larangote, Ana Maria de Melo, Guilherme Kamienski Lobermayer, Daniel Torrejón, Luciana Souza de Oliveira, Valeria Gonçalves Alvarenga, Dan Erick Vivas-Ruiz, Silvio Sanches Veiga, Eladio Flores Sanchez and Luiza Helena Gremski
Toxins 2024, 16(11), 486; https://doi.org/10.3390/toxins16110486 - 9 Nov 2024
Cited by 2 | Viewed by 2197
Abstract
Viperid snake venoms are notably abundant in metalloproteinases (proteins) (SVMPs), which are primarily responsible for inducing hemorrhage and disrupting the hemostatic process and tissue integrity in envenomed victims. In this study, barnettlysin-III (Bar-III), a hemorrhagic P-III SVMP, was purified from the venom of [...] Read more.
Viperid snake venoms are notably abundant in metalloproteinases (proteins) (SVMPs), which are primarily responsible for inducing hemorrhage and disrupting the hemostatic process and tissue integrity in envenomed victims. In this study, barnettlysin-III (Bar-III), a hemorrhagic P-III SVMP, was purified from the venom of the Peruvian snake Bothrops barnetti. Bar-III has a molecular mass of approximately 50 kDa and is a glycosylation-dependent functional metalloproteinase. Some biochemical properties of Bar-III, including the full amino acid sequence deduced from its cDNA, are reported. Its enzymatic activity is increased by Ca2+ ions and inhibited by an excess of Zn2+. Synthetic metalloproteinase inhibitors and EDTA also inhibit its proteolytic action. Bar-III degrades several plasma and ECM proteins, including fibrin(ogen), fibronectin, laminin, and nidogen. Platelets play a key role in hemostasis and thrombosis and in other biological process, such as inflammation and immunity, and platelet activation is driven by the platelet signaling receptors, glycoprotein (GP)Ib-IX-V, which binds vWF, and GPVI, which binds collagen. Moreover, Bar-III inhibits vWF- and convulxin-induced platelet aggregation in human washed platelets by cleaving the recombinant A1 domain of vWF and GPVI into a soluble ectodomain fraction of ~55 kDa (sGPVI). Bar-III does not reduce the viability of cultured endothelial cells; however, it interferes with the adhesion of these cells to fibronectin, vitronectin, and RGD peptides, as well as their migration profile. Bar-III binds specifically to the surface of these cells, and part of this interaction involves α5β1 integrin receptors. These results contribute to a better comprehension of the pathophysiology of snakebite accidents/incidents and could be used as a tool to explore novel and safer anti-venom therapeutics. Full article
(This article belongs to the Section Animal Venoms)
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