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Search Results (199)

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Keywords = human dermal fibroblast (HDF)

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27 pages, 21524 KiB  
Article
Synergistic Combinations of Native Australian Plants For Skin Inflammation and Wound Healing
by Rotina Kapini, Dennis Chang, Gerald Münch, Lisa Carroll and Xian Zhou
Biomedicines 2025, 13(7), 1754; https://doi.org/10.3390/biomedicines13071754 - 17 Jul 2025
Viewed by 468
Abstract
Background: Inflammation and oxidative stress are key mechanisms in underlying skin conditions like psoriasis and eczema. While many plants, including Australian native plants, are proposed to target these pathways due to their phytochemical content, studies on whole extracts and their synergistic effects remain [...] Read more.
Background: Inflammation and oxidative stress are key mechanisms in underlying skin conditions like psoriasis and eczema. While many plants, including Australian native plants, are proposed to target these pathways due to their phytochemical content, studies on whole extracts and their synergistic effects remain limited. Objectives: This study aimed to investigate individual and combined effects of whole plant extracts on skin protection and healing, focusing on their anti-inflammatory and antioxidant properties. Methods: The antioxidant potential of the individual and combined plant extracts were investigated on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reactive oxygen species (ROS) assay followed by luciferase assay in MCF-7 AREc32 cells for nuclear factor erythroid 2-related factor 2 (Nrf2) activation. The anti-inflammatory activities were investigated on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages for the inhibition of nitric oxide (NO), tumour necrosis factor (TNF)-α, and interleukin (IL)-6. Synergistic interaction was determined by the combination index model (CI < 1). Combination(s) showing synergistic and optimal activity were further investigated on LPS-induced human dermal fibroblasts (HDF) cells for IL-6 inhibition and wound healing activity. Results: Three of the tested Australian native plant extracts demonstrated prominent antioxidant and anti-inflammatory activities including bitter orange, mountain pepper berry and native river mint. In particular, their three-way combination (1:1:1, w/w) showed prominent synergistic (CI < 1) in reducing NO and IL-6, along with enhanced Nrf2 activation. In LPS-inflamed HDF cells, the combination maintained synergistic inhibition of IL-6 levels and promoted wound healing response. Conclusions: These findings highlight the therapeutic potential of Australian native plant as a whole extract for skin protection and repair attributed to antioxidant and anti-inflammatory activities. The observed synergistic anti-inflammatory and antioxidant effects support their use in the development of new cosmetic formulations for skin. Full article
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16 pages, 1884 KiB  
Article
The Mechanism of Protective Action of Plant-Derived Squalane (2,6,10,15,19,23-Hexamethyltetracosane) Against UVA Radiation-Induced Apoptosis in Human Dermal Fibroblasts
by Katarzyna Wolosik, Magda Chalecka, Gabriela Gasiewska, Jerzy Palka and Arkadiusz Surazynski
Antioxidants 2025, 14(7), 853; https://doi.org/10.3390/antiox14070853 - 11 Jul 2025
Viewed by 395
Abstract
Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced [...] Read more.
Ultraviolet A (UVA) radiation has been identified as a significant factor contributing to skin photoaging and skin diseases, operating through the excessive generation of reactive oxygen species (ROS) and the subsequent induction of DNA damage. Plant-derived antioxidants have demonstrated efficacy in mitigating UVA-induced damage; nevertheless, their instability limits their therapeutic potential. This study investigates the mechanisms of antioxidant and cytoprotective effects of squalane (Sq), a stable, plant-derived triterpene, in human dermal fibroblasts (HDFs) exposed to UVA radiation. Sq was administered at concentrations ranging from 0.005% to 0.015% prior to UVA exposure (10 J/cm2). It has been found that Sq counteracted UVA-induced ROS formation, decreased the level of reduced thiol groups, activated apoptosis, and inhibited DNA biosynthesis. Immunofluorescence analysis revealed that Sq suppressed the UVA-induced expression of p53, caspase-3, caspase-9, and PARP, while restoring the activity of the pro-survival p-Akt/mTOR pathway. The findings indicate that Sq exerts protective effects on UVA-induced fibroblast damage through a combination of antioxidant and anti-apoptotic mechanisms. Full article
(This article belongs to the Special Issue Antioxidant Phytochemicals for Promoting Human Health and Well-Being)
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16 pages, 2791 KiB  
Article
Low-Molecular-Weight Collagen Peptide Improves Skin Dehydration and Barrier Dysfunction in Human Dermal Fibrosis Cells and UVB-Exposed SKH-1 Hairless Mice
by Eunjung Choi, Heeyeon Joo, Myunghee Kim, Do-Un Kim, Hee-Chul Chung and Jae Gon Kim
Int. J. Mol. Sci. 2025, 26(13), 6427; https://doi.org/10.3390/ijms26136427 - 3 Jul 2025
Viewed by 690
Abstract
Ultraviolet B (UVB), a component of solar ultraviolet light, is a major contributor to skin photodamage. UVB exposure primarily affects the epidermis, which leads to wrinkle formation, loss of skin elasticity, oxidative stress, and inflammation. Prolonged or intense UVB exposure can increase the [...] Read more.
Ultraviolet B (UVB), a component of solar ultraviolet light, is a major contributor to skin photodamage. UVB exposure primarily affects the epidermis, which leads to wrinkle formation, loss of skin elasticity, oxidative stress, and inflammation. Prolonged or intense UVB exposure can increase the risk of skin cancer. Collagen peptides are known as functional foods that improve skin dryness and wound healing. In this study, we aimed to investigate the protective and ameliorative effects of a low-molecular-weight collagen peptide (LMWCP) with a high absorption rate and photodamage. In vitro analysis using human dermal fibroblasts (HDFs) demonstrated that LMWCP promoted skin protection by increasing procollagen type I production, enhancing cell proliferation and migration, and inhibiting MMP-1 activity. Furthermore, LMWCP intake was indicated by improved skin hydration, reduced trans-epidermal water loss (TEWL), and changes in the clinical parameters, including skin elasticity, erythema, and scaling scores in UVB-exposed hairless mice. In the UVB-damaged tissues, an increase in skin elasticity-related enzymes was observed along with a decrease in aging-related and pro-inflammatory gene expression. Histological analysis revealed an increase in collagen content and restoration of dermal thickness. These findings suggested that LMWCP has significant benefits in preventing and improving UVB-induced skin damage. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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30 pages, 7589 KiB  
Article
Plant-Based ZnO Nanoparticles for Green Nanobiocontrol of a Highly Virulent Bacterial Leaf Blight Pathogen: Mechanistic Insights and Biocompatibility Evaluation
by Preeda Chanthapong, Duangkamol Maensiri, Paweena Rangsrisak, Thanee Jaiyan, Kanchit Rahaeng, Atcha Oraintara, Kunthaya Ratchaphonsaenwong, Jirawat Sanitchon, Piyada Theerakulpisut and Wuttipong Mahakham
Nanomaterials 2025, 15(13), 1011; https://doi.org/10.3390/nano15131011 - 30 Jun 2025
Viewed by 1182
Abstract
Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a serious threat to rice cultivation. This study presents the green synthesis of zinc oxide nanoparticles (ZnO NPs) using an aqueous leaf extract of the medicinal plant Centella asiatica [...] Read more.
Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv. oryzae (Xoo), poses a serious threat to rice cultivation. This study presents the green synthesis of zinc oxide nanoparticles (ZnO NPs) using an aqueous leaf extract of the medicinal plant Centella asiatica (L.) Urban and evaluates their potential as dual-function nanopesticides. The synthesized CA-ZnO NPs exhibited high crystallinity, a hexagonal to quasi-spherical morphology, and nanoscale dimensions (~22.5 nm), as confirmed by UV–Vis spectroscopy, XRD, FTIR, SEM, TEM, and SAED analyses. These nanoparticles demonstrated potent antibacterial activity against a highly virulent, field-derived Thai Xoo strain, with a minimum inhibitory concentration (MIC) of 8 µg/mL. Mechanistic investigations revealed substantial membrane disruption, intracellular nanoparticle penetration, and elevated reactive oxygen species (ROS) generation in treated cells. Cytotoxicity testing using human dermal fibroblasts (HDFs) revealed excellent biocompatibility, with no statistically significant reduction in cell viability at concentrations up to 500 µg/mL. In contrast, viability markedly declined at 1000 µg/mL. These findings underscore the selective antibacterial efficacy and minimal mammalian cytotoxicity of CA-ZnO NPs. Overall, CA-ZnO NPs offer a promising green nanopesticide platform that integrates potent antibacterial activity with biocompatibility, supporting future applications in sustainable crop protection and biomedical nanotechnology. Full article
(This article belongs to the Topic Nano-Enabled Innovations in Agriculture)
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13 pages, 5576 KiB  
Article
Ribosome Incorporation Transdifferentiates Chick Primary Cells and Induces Their Proliferation by Secreting Growth Factors
by Shota Inoue, Arif Istiaq, Anamika Datta, Mengxue Lu, Shintaro Nakayama, Kousei Takashi, Nobushige Nakajo, Shigehiko Tamura, Ikko Kawashima and Kunimasa Ohta
J. Dev. Biol. 2025, 13(2), 19; https://doi.org/10.3390/jdb13020019 - 1 Jun 2025
Viewed by 3614
Abstract
Previously, we reported that mammalian cells, specifically human dermal fibroblasts (HDFs), could be transdifferentiated by lactic acid bacteria (LAB). Later, we observed that HDFs incorporated LAB-derived ribosomes, forming the ribosome-induced cell clusters (RICs) and transdifferentiating into cells derived from all three germ layers. [...] Read more.
Previously, we reported that mammalian cells, specifically human dermal fibroblasts (HDFs), could be transdifferentiated by lactic acid bacteria (LAB). Later, we observed that HDFs incorporated LAB-derived ribosomes, forming the ribosome-induced cell clusters (RICs) and transdifferentiating into cells derived from all three germ layers. Based on this insight, we hypothesized that incorporating ribosomes into non-mammalian cells could reveal the universality of this mechanism and open the door to commercial applications. Our current study demonstrates that ribosome incorporation can transdifferentiate chick primary muscle-derived cells (CMCs) into adipocytes, osteoblasts, and chondrocytes. Furthermore, the culture medium supernatant from ribosome-incorporated CMCs was found to significantly enhance CMC’s proliferation. RNA-seq analysis revealed that RICs-CMC exhibit increased expression of genes related to multi-lineage cell growth. In addition, we developed a novel technological shift in meat production—the “CulNet System”—which replicates organ interactions within mechanical systems for cell-cultured meat production. While significant efforts are still required to implement this technology in a cost-effective manner, we believe that combining the “CulNet System” with ribosome-incorporated multipotent cells that have prolonged culture capability could substantially improve the scalability and cost-effectiveness of cultured chicken meat production. This report highlights a promising approach for cell-culture-based meat production, offering a sustainable alternative to traditional methods. Full article
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21 pages, 5231 KiB  
Article
Clarithromycin-Loaded Albumin-Based Nanoparticles for Improved Antibacterial and Anticancer Performance
by Walhan Alshaer, Shrouq Alsotari, Nour Aladaileh, Alaa Rifai, Aya Khalaf, Baidaa AlQuaissi, Bushra Sabbah, Hamdi Nsairat and Fadwa Odeh
Pharmaceutics 2025, 17(6), 729; https://doi.org/10.3390/pharmaceutics17060729 - 31 May 2025
Viewed by 1516
Abstract
Background/Objectives: Clarithromycin (CLA) is a widely used antibiotic effective against a variety of bacterial strains, making it a common treatment for respiratory, skin, and soft tissue infections. Moreover, extensive studies have confirmed the anticancer activity of CLA against different cancers, particularly when combined [...] Read more.
Background/Objectives: Clarithromycin (CLA) is a widely used antibiotic effective against a variety of bacterial strains, making it a common treatment for respiratory, skin, and soft tissue infections. Moreover, extensive studies have confirmed the anticancer activity of CLA against different cancers, particularly when combined with conventional therapies. This study investigates the potential anticancer and antibacterial activities of developed CLA-loaded bovine serum albumin nanoparticles (CLA-BSA NPs), designed with optimized physicochemical properties to enhance drug delivery. Methods: The CLA-BSA NPs were synthesized using the desolvation method, followed by drug loading. Characterization techniques, including Dynamic Light Scattering (DLS), Fourier-Transform Infrared (FTIR) Spectroscopy, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Thermogravimetric Analysis (TGA). Results: The results confirmed that CLA interacts with BSA NPs through van der Waals forces. The performance of drug–nanocarrier interaction was further assessed through in vitro drug release studies. The release studies demonstrated that CLA had a robust release profile in reductive media, with a cumulative release of 50.9% in acetate buffer (pH 5.0) supplemented with 10 mM glutathione (GSH). Further biological activity assays were also conducted, including cell viability assays (MTT) and antibacterial activity tests. CLA-BSA NPs demonstrated anticancer activity against the lung cancer (A549) cell line, while showing minimal cytotoxicity on normal human dermal fibroblast (HDF) cells. The antibacterial activity was assessed against Streptococcus pyogenes, Bacillus cereus, and Staphylococcus aureus. Among the tested strains, Bacillus cereus exhibited the highest sensitivity, with a minimum inhibitory concentration (MIC) of 0.032 µg/mL, compared to 0.12 µg/mL for Staphylococcus aureus and >32 µg/mL for Streptococcus pyogenes. Conclusions: In conclusion, these findings highlight CLA-BSA NPs as a promising drug delivery system that enhances the anticancer and antibacterial efficacy of CLA. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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13 pages, 1467 KiB  
Article
Flavonoids Identified in Terminalia spp. Inhibit Gastrointestinal Pathogens and Potentiate Conventional Antibiotics via Efflux Pump Inhibition
by Muhammad Jawad Zai, Matthew James Cheesman and Ian Edwin Cock
Molecules 2025, 30(11), 2300; https://doi.org/10.3390/molecules30112300 - 23 May 2025
Viewed by 520
Abstract
The genus Terminalia has a long history of use in traditional medicine to treat various diseases, including bacterial infections. We previously reported a metabolomic analysis using liquid chromatography–mass spectrometry of selected Australian Terminalia spp. and highlighted numerous flavonoids that may contribute to the [...] Read more.
The genus Terminalia has a long history of use in traditional medicine to treat various diseases, including bacterial infections. We previously reported a metabolomic analysis using liquid chromatography–mass spectrometry of selected Australian Terminalia spp. and highlighted numerous flavonoids that may contribute to the antimicrobial activities of those plants. This study examines the antibacterial activities of fifteen flavonoids found in Terminalia spp. against a range of gastrointestinal pathogens using broth dilution assays. Flavonoids were also combined with six different classes of conventional antibiotics to investigate interactions. The efflux pump inhibitory activity of the flavonoid was evaluated using ethidium bromide accumulation and efflux assays. Toxicities were assessed via human dermal fibroblast cell line assays. Fisetin, hispidulin, isoorientin, orientin, rutin, and vitexin showed noteworthy growth inhibitory activity (MIC values 62.5–250 µg/mL). Isoorientin and orientin were most potent against Bacillus cereus and Alcaligenes faecalis, displaying MIC values of 62.5 µg/mL against both bacteria. All flavonoids except genistein, isorhamnetin, kaempferol, luteolin, taxifolin, and vitexin were nontoxic in human dermal fibroblast (HDF) cell proliferation assays. When individual flavonoids were combined with selected antibiotics, some potentiated the activity of these antibiotics. Two synergistic, eighteen additive and thirty-one non-interactive interactions were observed. The synergistic interactions were all observed in combination with orientin. Notably, orientin exhibited efflux pump inhibitory effects at concentrations from 15.26 µg/mL to 125 µg/mL. The findings reported herein indicate that the selected flavonoids have the potential for addressing bacterial antibiotic resistance and highlight the need for further study. Full article
(This article belongs to the Special Issue Natural Products and Microbiology in Human Health)
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14 pages, 1241 KiB  
Article
Inhibition of TNF-α-Induced Collagen Degradation and Oxidative Damage by Centipeda minima and Brevilin A in Human Dermal Fibroblasts
by Sullim Lee, Byoung Ha Kim, Yea Jung Choi, Dong-Wook Kim, Eunsu Cho, Moonseok Kang, Doeun Kim, Jaesung Pyo and Ki Sung Kang
Curr. Issues Mol. Biol. 2025, 47(5), 376; https://doi.org/10.3390/cimb47050376 - 20 May 2025
Viewed by 583
Abstract
Skin aging and inflammatory skin lesions are exacerbated by reactive oxygen species (ROS) generated in the mitochondria of human dermal fibroblasts (HDFs). These oxidative stressors degrade the extracellular matrix (ECM), promote inflammation, and accelerate skin aging. Antioxidants that suppress reactive oxygen species (ROS) [...] Read more.
Skin aging and inflammatory skin lesions are exacerbated by reactive oxygen species (ROS) generated in the mitochondria of human dermal fibroblasts (HDFs). These oxidative stressors degrade the extracellular matrix (ECM), promote inflammation, and accelerate skin aging. Antioxidants that suppress reactive oxygen species (ROS) production play a crucial role in mitigating these effects. This study investigated the protective effects of Centipeda minima (CMX) and its active constituent, brevilin A, against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and ECM degradation in normal human dermal fibroblasts (NHDFs). Both CMX and brevilin A significantly inhibited TNF-α-induced elevations in ROS, nitric oxide (NO), and prostaglandin E2 (PGE2) levels, thereby reducing oxidative stress and inflammatory responses. Additionally, they effectively suppressed matrix metalloproteinase-1 (MMP-1) expression and restored the procollagen I α1 (COLIA1) levels, indicating their potential to preserve ECM integrity. Mechanistically, brevilin A selectively inhibited ERK phosphorylation in the mitogen-activated protein kinase (MAPK) pathway, suggesting its role in regulating collagen degradation and inflammation. These findings highlight that CMX and brevilin A are promising natural agents for protection against skin aging and inflammation. However, further in vivo studies are necessary to validate their efficacy and explore their potential applications in dermatological formulations. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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21 pages, 4025 KiB  
Article
Proliferation of Human Cervical Cancer Cells Responds to Surface Properties of Bicomponent Polymer Coatings
by Emil Rosqvist, Erik Niemelä, Shujun Liang, John E. Eriksson, Xiaoju Wang and Jouko Peltonen
Nanomaterials 2025, 15(10), 716; https://doi.org/10.3390/nano15100716 - 9 May 2025
Viewed by 536
Abstract
The proliferation of human cervical cancer (Hela) cells was investigated on a series of nanostructured polymer latex surfaces. The physico-chemical properties of the surfaces, composed of mixtures of polystyrene and acrylonitrile butadiene styrene dispersions, were precisely controlled in the nanoscale range by adjusting [...] Read more.
The proliferation of human cervical cancer (Hela) cells was investigated on a series of nanostructured polymer latex surfaces. The physico-chemical properties of the surfaces, composed of mixtures of polystyrene and acrylonitrile butadiene styrene dispersions, were precisely controlled in the nanoscale range by adjusting the mixing ratio of the components and thermal treatment. In addition, the proliferation response of HeLa cells was compared to that of human dermal fibroblast (HDF) cells. A low dispersive surface energy and peak or valley dominance (Spk/Svk) were observed to increase the proliferation yield of the Hela cells. The HDF cells were less influenced by the surface chemistry and showed improved proliferation on surfaces without dominant peak or valley features (Spk and Svk). The observed changes in Hela cell behaviour underscored the critical role of material surface properties in influencing cellular responses, with more significant accumulation of nuclear patterning of filamentous actin (F-actin) on stiffer and smoother surfaces (e.g., borosilicate glass) due to higher mechanical stress. A more dynamic reorganisation of the cytoskeleton was observed for cells grown on polymer surfaces with moderate roughness and surface energy. These results emphasise the importance of characterising and tuning surface properties to accommodate the specific behaviours of different cell types. Full article
(This article belongs to the Section Synthesis, Interfaces and Nanostructures)
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17 pages, 4185 KiB  
Article
Squalane as a Promising Agent Protecting UV-Induced Inhibition of Collagen Biosynthesis and Wound Healing in Human Dermal Fibroblast
by Katarzyna Wolosik, Magda Chalecka, Gabriela Gasiewska, Jerzy Palka and Arkadiusz Surazynski
Molecules 2025, 30(9), 1964; https://doi.org/10.3390/molecules30091964 - 29 Apr 2025
Cited by 1 | Viewed by 1806
Abstract
Squalane, a highly stable derivative of squalene, has received attention for its potential application in dermatology and cosmetics due to its biocompatibility, moisturizing properties, and antioxidant activity. This study investigates the effects of squalane on UVA-induced oxidative stress, inflammation, deregulation of collagen metabolism, [...] Read more.
Squalane, a highly stable derivative of squalene, has received attention for its potential application in dermatology and cosmetics due to its biocompatibility, moisturizing properties, and antioxidant activity. This study investigates the effects of squalane on UVA-induced oxidative stress, inflammation, deregulation of collagen metabolism, and some growth signaling pathways in human dermal fibroblasts (HDFs). It has been found that squalane at concentrations of 0.005–0.015% counteracted the UVA-induced inhibition of oxidative stress, collagen biosynthesis, prolidase activity, expression of the β1-integrin receptor, insulin-like growth factor-I receptor (IGFR), transforming growth factor-β (TGF-β), phosphorylated kinases ERK1/2, and increase in the expression of p38 kinase in HDFs. Moreover, squalane at the studied concentrations counteracted UVA-induced increase in the expression of NF-κB and COX-2 in HDFs, suggesting its anti-inflammatory activity. Interestingly, squalane augmented the UVA-induced expression of nuclear factor erythroid 2-related factor 2 (Nrf2). The functional significance of squalane activities was found in a model of wound healing in HDFs. Squalane at the studied concentrations stimulated fibroblast migration, facilitating the repair process following exposure of the cells to UVA radiation. These results demonstrate the ability of squalane to counteract UVA-induced cell damage and suggest its potential to support skin regeneration, highlighting its application in anti-aging, post-sun repair, and regenerative care formulations. Full article
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17 pages, 5837 KiB  
Article
Therapeutic Effects of Sigesbeckia pubescens Makino Against Atopic Dermatitis-Like Skin Inflammation Through the JAK2/STAT Signaling Pathway
by Hyun-Kyung Song, Hye Jin Kim, Seong Cheol Kim and Taesoo Kim
Int. J. Mol. Sci. 2025, 26(9), 4191; https://doi.org/10.3390/ijms26094191 - 28 Apr 2025
Cited by 2 | Viewed by 493
Abstract
Atopic dermatitis (AD), a chronic inflammatory skin condition, is a common allergic disorder. The human skin, the largest organ, serves as the first barrier in protecting the body against various external threats. Human epidermal keratinocytes (HEKs) in the epidermal layer and human dermal [...] Read more.
Atopic dermatitis (AD), a chronic inflammatory skin condition, is a common allergic disorder. The human skin, the largest organ, serves as the first barrier in protecting the body against various external threats. Human epidermal keratinocytes (HEKs) in the epidermal layer and human dermal fibroblasts (HDFs) in the dermis of the skin are implicated in AD-associated skin inflammation through the secretion of diverse inflammatory mediators, including chemokines. Sigesbeckia pubescens Makino (SP), a traditional Korean and Chinese herbal remedy, is used for treating inflammatory conditions. While several pharmacological effects of SP extract (SPE) have been documented, its specific inhibitory effect on AD-related skin inflammation remains unexplored. Hence, oral administration of SPE to NC/Nga mice reduced the severity of house dust mite extract-induced dermatitis, accompanied by lowered levels of serum inflammatory mediators, decreased epidermal thickness, reduced mast cell infiltration, and restoration of skin barrier function within skin lesions. In conclusion, SPE has demonstrated the ability to alleviate skin inflammation and protect the skin barrier and shows potential as a therapeutic option for AD. SPE inhibited proinflammatory chemokine production by modulating the Janus kinase (JAK) 2/signal transducer and activator of transcription proteins (STAT) 1/STAT3 signaling pathway in IFN-γ- and TNF-α-stimulated skin cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Targets in Skin Diseases)
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12 pages, 2025 KiB  
Article
3D Spheroid Cultures for Salivary Gland Tissue Engineering: Effects of Fibroblast on Epithelial Cell Function
by Lan Thi Phuong Nguyen, Joo Hyun Kim, Jiwon Son, Sung Sik Hur, Minyong Lee, Hyung Kwon Byeon, Jin-Young Kim, Myung Jin Ban, Joo Hyun Kim, Man Ryul Lee, Jae Hong Park and Yongsung Hwang
Life 2025, 15(4), 607; https://doi.org/10.3390/life15040607 - 5 Apr 2025
Viewed by 1206
Abstract
Three-dimensional (3D) spheroid cultures are crucial for modeling salivary gland (SG) morphogenesis and advancing regenerative medicine. This study evaluated the effects of varying ratios of mouse SG-derived epithelial cells co-cultured with human dermal fibroblasts (hDFs), identifying a 2:1 ratio (spheroids containing 67% EpCAM [...] Read more.
Three-dimensional (3D) spheroid cultures are crucial for modeling salivary gland (SG) morphogenesis and advancing regenerative medicine. This study evaluated the effects of varying ratios of mouse SG-derived epithelial cells co-cultured with human dermal fibroblasts (hDFs), identifying a 2:1 ratio (spheroids containing 67% EpCAMpos cells with 33% hDFs) as optimal for preserving native SG-derived epithelial cell phenotypes. At this ratio, 67% EpCAMpos spheroids maintained structural integrity and demonstrated a significant reduction in apoptosis and senescence markers, specifically, cleaved caspase-3 (Cc3) and Serpine1, alongside an enhanced expression of the progenitor marker Keratin 5 (KRT5). This highlights the pivotal role of fibroblasts in supporting epithelial cell function in 3D cultures. These spheroids provide a useful model for developing SG tissues that closely mimic physiological properties. Despite promising results, these findings are preliminary and require further validation under diverse conditions and across different SG models. Full article
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20 pages, 6144 KiB  
Article
Remote Co-Loading of Doxorubicin and Hydralazine into PEGylated Liposomes: In Vitro Anti-Proliferative Effect Against Breast Cancer
by Walhan Alshaer, Zainab Lafi, Hamdi Nsairat, Baidaa AlQuaissi, Dana A. Alqudah, Hadil Zureigat and Islam Hamad
Molecules 2025, 30(7), 1549; https://doi.org/10.3390/molecules30071549 - 31 Mar 2025
Cited by 1 | Viewed by 1250
Abstract
Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for the use of a reduced DOX dose. The current study describes the remote [...] Read more.
Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for the use of a reduced DOX dose. The current study describes the remote co-loading of DOX and HDZ into PEGylated liposomes using, for the first time, a simultaneous pH gradient technique. First, PEGylated liposomes were prepared using an ethanol injection method and remotely loaded with DOX and HDZ. Then, DOX- and HDZ-loaded liposomes (Lip-DOX-HDZ) were characterized using DLS, TEM, FTIR, thermal analysis, drug leakage, and stability. Furthermore, the cellular uptake and cytotoxicity were evaluated in two human breast cancer cell lines (MCF7 and MDA-MB-231) and two normal cell lines (human dermal fibroblasts (HDFs) and rat cardiac cells (H9C2)). The results revealed that Lip-DOX-HDZ had a particle size of 158 ± 18 nm, PDI of 0.22 ± 0.08, and zeta potential of −22 ± 5 mV. The encapsulation efficiency of DOX and HDZ was 90% and 30%, respectively. Moreover, the IC50 values of Lip-DOX-HDZ showed higher cytotoxicity against the MDA-MB-231 (5.5 ± 0.4 µM) and MCF7 (6.25 ± 0.9 µM) breast cancer cell lines compared to normal cells: HDF cells (20 ± 3.0 µM) and H9C2 cardiac cells (19.37 ± 2.0 µM). Our study found that remotely loaded Lip-DOX-HDZ showed a ~4-fold lower toxicity and selectivity for normal cells (HDFs and H9C2), compared to breast cancer cells. This suggests that Lip-DOX-HDZ is a promising nanocarrier for both DOX and HDZ, clinically potent molecules. Full article
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19 pages, 3588 KiB  
Article
A Proprietary Punica granatum pericarp Extract, Its Antioxidant Properties Using Multi-Radical Assays and Protection Against UVA-Induced Damages in a Reconstructed Human Skin Model
by Steve Thomas Pannakal, Steven Durand, Julie Gizard, Peggy Sextius, Emilie Planel, Emilie Warrick, Damien Lelievre, Celine Lelievre, Joan Eilstein, Floriane Beaumard, Arpita Prasad, Sanketh Shetty, Arun Duraisamy, Kumar Gaurav, Sherluck John, Adrien Benazzouz, Xavier Fastinger, Dhimoy Roy and Vishal Sharma
Antioxidants 2025, 14(3), 301; https://doi.org/10.3390/antiox14030301 - 28 Feb 2025
Viewed by 1763
Abstract
Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with [...] Read more.
Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with both epidermal and dermal damage resulting from the generation of reactive oxygen species (ROS). Among them, the longest UVA wavelengths (UVA1, 340–400 nm) can represent up to 75% of the total UV energy. Therefore, UVA radiation is linked to various acute and chronic conditions, including increased skin pigmentation and photoaging. Despite many advances in the skin photoprotection category, there is still a growing demand for natural daily photoprotection active ingredients that offer broad protection against skin damage caused by UVA exposure. In our quest to discover new, disruptive, next generation of photoprotective ingredients, we were drawn to pomegranate, based on its diverse polyphenolic profile. We investigated the pericarp of the fruit, so far considered as byproducts of the pomegranate supply chain, to design a novel patented extract “POMAOX” with a desired spectrum of phenolic components comprising of αβ-punicalagins, αβ-punicalins and ellagic acid. Methods: Antioxidant properties of POMAOX were measured using in-tubo standard tests capable of revealing a battery of radical oxygen species (ROS): peroxyl radical (ORAC), singlet oxygen (SOAC), superoxide anion (SORAC), peroxynitrite (NORAC), and hydroxyl radical (HORAC). In vitro, confirmation of antioxidant properties was first performed by evaluating protection against UVA-induced lipid peroxidation in human dermal fibroblasts (HDF), via the release of 8 iso-prostanes. The protection offered by POMAOX was further validated in a 3D in vitro reconstructed T-SkinTM model, by analyzing tissue viability/morphology and measuring the release of Matrix Metallopeptidase 1 (MMP-1) & pro-inflammatory mediators (IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNF-α) after UVA1 exposure. Results: POMAOX displayed strong antioxidant activity against peroxynitrite (NORAC) at 1.0–3.0 ppm, comparable to the reference vitaminC, as well as singlet oxygen (SOAC) at 220 ppm, and superoxide radicals with a SORAC value of 500 ppm. Additionally, POMAOX demonstrated strong photoprotection benefit at 0.001% concentration, offering up to 74% protection against UVA-induced lipid peroxidation on HDF, in a similar range as the positive reference, Vitamin E at 0.002% (50 µM), and with higher efficacy than ellagic acid alone at 5 µM. Moreover, our pomegranate-derived extract delivered photoprotection at 0.001%, mitigating dermal damages induced by UVA1, through inhibition of MMP-1 and significant inhibition of pro-inflammatory mediators release (including IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNFα) on an in vitro reconstructed full-thickness human skin model with a similar level of protection to that of Vitamin C tested at 0.035% (200 µM). Conclusions: Overall, the novel pomegranate-derived extract “POMAOX” significantly reduced the impact of UVA on human skin, due to its broad-spectrum antioxidant profile. These findings suggest that POMAOX could offer enhanced protection against the detrimental effects of UV exposure, addressing the growing consumer demand for strong photoprotection with skincare benefits. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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14 pages, 4662 KiB  
Article
Enhanced Antioxidant and Protective Effects of Fermented Solanum melongena L. Peel Extracts Against Ultraviolet B-Induced Skin Damage
by Joo Hwa Lee, Jinsick Kim, Yu Chang Jo, Yun Hoo Jo, Yeong Hwan Jeong, Soo Ah Jeong, Beong Ou Lim and Dong Wook Shin
Nutrients 2025, 17(5), 847; https://doi.org/10.3390/nu17050847 - 28 Feb 2025
Viewed by 962
Abstract
Background/Objectives: The skin, being the body’s outermost organ, plays a vital role in protecting against various external stimuli. Ultraviolet generates reactive oxygen species (ROS), promoting the secretion of matrix metalloproteinases (MMPs) and inducing collagen degradation. Many studies have been conducted to identify [...] Read more.
Background/Objectives: The skin, being the body’s outermost organ, plays a vital role in protecting against various external stimuli. Ultraviolet generates reactive oxygen species (ROS), promoting the secretion of matrix metalloproteinases (MMPs) and inducing collagen degradation. Many studies have been conducted to identify natural substances that can prevent or delay the harmful effects of UV. Methods: A wound healing assay, DCF-DA reactive oxygen species (ROS) assay, and JC-1 assay were performed to assess the effects of bio-converted eggplant peels (BEPs) on human dermal fibroblasts (HDFs). Western blot analysis was also conducted to understand the underlying mechanisms for their effects. Finally, hematoxylin–eosin staining and immunohistochemistry were also performed in animal studies. Results: Our study evaluated the antioxidant efficacy of BEPs fermented with Lactobacillus plantarum in hydrogen peroxide (H2O2)-HDFs and UVB-induced skin damage in hairless mice. We demonstrated that BEPs exhibited enhanced antioxidant properties compared to non-fermented eggplant peels (EPs). BEPs facilitated wound healing in H2O2-damaged HDFs, reduced ROS levels, and restored mitochondrial membrane potential. BEPs suppressed the phosphorylation of ERK, p38, and JNK as their underlying mechanism. We further demonstrated that dietary supplementation of BEPs also downregulated matrix metalloproteinase 1 (MMP1) expression and upregulated collagen I (COL1) in UVB-damaged hairless mice, indicating that BEPs were more effective compared to EPs. Conclusions: Our studies suggest that BEPs fermented with Lactobacillus plantarum hold significant potential as a protective agent for mitigating UVB-induced damage and promoting skin health. Full article
(This article belongs to the Special Issue Relationships between Dietary Factors and Inflammatory Skin Diseases)
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