Search Results (1,860)

Skin aging is closely related to mitochondrial dysfunction and cell cycle abnormalities, and developing intervention strategies targeting mitochondrial quality control is an important direction for anti-aging research. In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated β-galactosidase (SA-β-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control. Full article

Various biomaterials are currently employed for dermal biostimulation and filling purposes, with hyaluronic acid (HA)-based fillers among those with the most favorable safety profile, albeit exhibiting a limited biostimulatory effect. This study suggests that hyaluronic acid and succinic acid (SA) can significantly induce beneficial effects on skin cells by targeting key aging hallmarks. Human dermal senescent fibroblasts and aged adipocytes were treated with HA + SA, and various aging characteristics were examined through gene expression analysis and microscopy staining. HA was found to stimulate autophagy gene expression, while SA modulated senescence-gene expression, and the combination of these compounds induced mitophagy in senescent fibroblasts. Additionally, the HA + SA promoted adipogenesis, increased IGF1, and decreased TNFA gene expression in aged adipocytes. Furthermore, the conditioned medium from adipocytes treated with HA + SA upregulated key dermal genes such as COL3A1 and EGF. The findings of this study suggest that HA and SA compounds can be used for the biostimulation of aged skin through the regulation of senescence-associated gene expression and cell communication between dermal fibroblasts and subcutaneous adipocytes. Full article

Bassia scoparia (Syn. Kochia scoparia (L.) Schrad.) is a medicinal plant whose fruit, Kochiae Fructus, has been extensively studied for its dermatological applications. This study focused on extracts from the whole plant B. scoparia (WPBS), excluding fruits, to address the research gap regarding the medicinal properties of non-fruit parts. The diverse skin benefits of WPBS, including its anti-photoaging, moisturizing, wound healing, anti-inflammatory, and anti-angiogenic effects, were investigated. The WPBS extract enhanced the viability of keratinocytes (HaCaT) without inducing cytotoxic effects. WPBS significantly reduced matrix metalloproteinase-1 (MMP-1) levels and increased collagen type I alpha 1 (COL1A1) levels (p < 0.01) in fibroblasts exposed to ultraviolet B (UVB) radiation, indicating strong anti-photoaging effects. WPBS upregulated skin hydration markers such as aquaporin-3 (AQP3) and hyaluronan synthase-3 (HAS3) and effectively accelerated fibroblast wound closure compared to the positive control. Furthermore, WPBS substantially downregulated the expression of inflammatory (COX-2 and IL-1β) and angiogenic markers (VEGF). Transcriptome analysis (RNA-seq) confirmed that WPBS suppressed inflammation-related and UV-induced gene expression pathways. Overall, these findings expand the therapeutic scope of B. scoparia beyond its traditional fruit use and suggest that WPBS is a promising botanical ingredient for various skin applications. Full article

Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic cellular dysfunction. While autophagy and inflammation are key dysregulated pathways in HGPS, the role of microRNAs (miRNAs) in these processes remains poorly understood. Methods: We performed an extensive literature review to identify miRNAs involved in autophagy and inflammation. Through stem-loop RT-qPCR in aging HGPS and control fibroblast strains, we identified significant miRNAs and focused on the most prominent one, miR-181a-5p, for in-depth analysis. We validated our in vitro findings with miRNA expression studies in skin biopsies from an HGPS mouse model and conducted functional assays in human fibroblasts, including immunofluorescence staining, β-Galactosidase assay, qPCR, and Western blot analysis. Transfection studies were performed using an miR-181a-5p mimic and its inhibitor. Results: We identified miR-181a-5p as a critical regulator of premature senescence in HGPS. miR-181a-5p was significantly upregulated in HGPS fibroblasts and an HGPS mouse model, correlating with Sirtuin 1 (SIRT1) suppression and induction of senescence. Additionally, we demonstrated that TGFβ1 induced miR-181a-5p expression, linking inflammation to miRNA-mediated senescence. Inhibiting miR-181a-5p restored SIRT1 levels, increased proliferation, and alleviated senescence in HGPS fibroblasts, supporting its functional relevance in disease progression. Conclusions: These findings highlight the important role of miR-181a-5p in premature aging and suggest its potential as a therapeutic target for modulating senescence in progeroid syndromes. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Aloe vera gel is a valuable raw material used in the cosmetic industry for its skin care properties. The present study analyzed the effects of the fermentation of aloe vera gel with a tea fungus kombucha, which is a symbiotic consortium of bacteria and yeast, carried out for 10 and 20 days (samples F10 and F20, respectively). The resulting ferments and unfermented gel were subjected to chromatographic analysis to determine the content of biologically active compounds. The permeability and accumulation of these compounds in pig skin were evaluated. In addition, the methods of DPPH, ABTS and the determination of intracellular free radical levels in keratinocytes (HaCaT) and fibroblasts (HDF) cell lines were used to determine antioxidant potential. The results showed a higher content of phenolic acids and flavonoids and better antioxidant properties of the ferments, especially after 20 days of fermentation. Cytotoxicity tests against HaCaT and HDF cells confirmed the absence of toxic effects; moreover, samples at the concentrations tested (mainly 10 and 25 mg/mL) showed cytoprotective effects. The analysis of enzymatic activity (collagenase, elastase and hyaluronidase) by the ELISA technique showed higher levels of inhibition for F10 and F20. The kombucha ferments also exhibited better moisturizing properties and lower levels of transepidermal water loss (TEWL), confirming their cosmetic potential. Full article

Traditional wound and burn treatments often fall short in balancing antimicrobial efficacy, patient comfort, and ease of application. This study introduces a novel, transparent, thermoresponsive sol–gel formulation incorporating polyhexamethylene biguanide (PHMB) for advanced topical therapy. Utilizing Poloxamer 407 as a biocompatible carrier, the formulation remains a sprayable liquid at room temperature and instantly gels upon contact with body temperature, enabling painless, pressure-free application on sensitive, injured skin. Comprehensive in vitro and in vivo evaluations confirmed the formulation’s broad-spectrum antimicrobial efficacy (≥5 log₁₀ reduction in 30 s), high biocompatibility (viability > 70% in fibroblasts), non-irritancy (OECD 425-compliant), and physical stability across three months. Importantly, the formulation maintained fibroblast migration capacity—crucial for wound regeneration—while exhibiting rapid sol-to-gel transition at ~34 °C. These findings highlight the system’s potential as a next-generation wound dressing with enhanced user compliance, transparent monitoring capability, and rapid healing support, particularly in disaster or emergency scenarios. Full article

Background: Blackberry seed oil (BSO), obtained from Rubus spp. Xavante cultivar via supercritical CO₂ extraction, contains bioactive lipids and antioxidants, but its cosmetic application is limited by poor solubility and stability. Nanoencapsulation with poly(ε-caprolactone) (PCL) can overcome these limitations. Methods: BSO was characterized by Ultra-High-Performance Liquid Chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and incorporated into PCL nanocapsules (NCBSO) using the preformed polymer deposition method. Physicochemical properties, stability (at 4 °C, room temperature, and 37 °C for 90 days), cytotoxicity, and collagen production were assessed in human fibroblasts. Additionally, a predictive in silico analysis using PASS Online, Molinspiration, and SEA platforms was performed to identify the bioactivities of major BSO compounds related to collagen synthesis, antioxidant potential, and anti-aging effects. Results: NCBSO showed a nanometric size of ~267 nm, low polydispersity (PDI < 0.2), negative zeta potential (−28 mV), and spherical morphology confirmed by FE-SEM. The dispersion remained stable across all tested temperatures, preserving pH and colloidal properties. In particular, BSO and NCBSO at 100 µg.mL⁻¹ significantly enhanced in vitro collagen production by 170% and 200%, respectively, compared to untreated cells (p < 0.01). Superior bioactivity was observed for NCBSO. The in silico results support the role of key compounds in promoting collagen biosynthesis and protecting skin structure. No cytotoxic effects were achieved. Conclusions: The nanoencapsulation of BSO into PCL nanocapsules ensured formulation stability and potentiated collagen production. These findings support the potential of NCBSO as a promising candidate for future development as a collagen-boosting cosmeceutical. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article

Patients undergoing epidermal growth factor receptor inhibitor (EGFRI) therapy frequently experience dermatologic side effects, notably papulopustular rash, which impacts 50–90% of recipients. This rash typically appears on the face, chest, and back within weeks of treatment, resembling acne but stemming from distinct pathophysiological mechanisms, causing significant discomfort and reduced quality of life. Prophylactic measures and symptom-based treatment are recommended, emphasizing patient education, topical agents, and systemic therapies for severe cases. A 41-year-old female with advanced colonic mucinous adenocarcinoma developed severe acneiform rash and pruritus during EGFRI therapy with panitumumab. Initial standard treatment with oral doxycycline was discontinued after two days due to severe gastrointestinal intolerance characterized by intense nausea and dyspepsia. With limited access to dermatological consultation, treatment with rose stem cell-derived exosomes (RSCEs) provided rapid symptom relief. Significant improvement was observed within 24 h, with complete resolution of pruritus and substantial reduction in inflammatory lesions within 72 h. RSCEs demonstrate anti-inflammatory effects through the modulation of pro-inflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, while promoting fibroblast proliferation and collagen synthesis enhancement. They may represent a possible alternative to corticosteroids, avoiding associated side effects such as skin atrophy, delayed wound healing, and local immunosuppression. This case underscores the potential of innovative treatments like RSCEs in managing EGFRI-induced skin complications when standard therapies are not tolerated, particularly in healthcare systems with limited dermato-oncological resources. Full article

Tissue-resident macrophages are essential for skin homeostasis. This study investigated whether lipopolysaccharide (LPS)-activated macrophages affect senescence and rejuvenation in human dermal fibroblasts. Human monocytic THP-1 cells were stimulated with Pantoea agglomerans–derived LPS (1–1000 ng/mL), and culture supernatants were collected. These were applied to two NB1RGB fibroblast populations: young, actively dividing cells (Young cells) and senescent cells with high population doubling levels and reduced proliferation (Old cells). Senescence markers P16, P21, and Ki-67 were analyzed at gene and protein levels. Conditioned medium from Old cells induced senescence in Young cells, increasing P16 and P21 expression levels. This effect was suppressed by cotreatment with LPS-activated THP-1 supernatant. Old cells treated with the LPS-activated supernatant exhibited decreased P16 and P21 levels as well as increased Ki-67 expression, indicating partial rejuvenation. These effects were not observed following treatment with unstimulated THP-1 supernatants or LPS alone. Overall, these findings suggest that secretory factors from LPS-activated macrophages can suppress cellular senescence and promote human dermal fibroblast rejuvenation, highlighting the potential role of macrophage activation in regulating cellular aging and offering a promising strategy for skin aging intervention. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Background/Objectives. Chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis, require safe and effective topical treatments. This study aimed to develop and evaluate a novel anti-inflammatory emulsion enriched with menthol, capsaicin, amino acids (glycine, arginine, histidine), and boswellic acid. Methods. Three formulations were prepared: a control (E1), a partial (E2), and a comprehensive formulation (E3). Physicochemical analyses included texture profiling, rheological behavior, pH stability, moisture content, and particle size distribution. Results. E3 demonstrated superior colloidal stability, optimal pH (5.75–6.25), and homogenous droplet size (<1 µm), indicating favorable dermal delivery potential. Ex vivo permeation studies revealed effective skin penetration of menthol and amino acids, with boswellic acid remaining primarily in the epidermis, suggesting localized action. Under oxidative stress conditions, E3 significantly improved fibroblast viability, indicating synergistic cytoprotective effects of combined active ingredients. While individual compounds showed limited or dose-dependent efficacy, their combination restored cell viability to near-control levels. Conclusions. These findings support the potential of this multi-component emulsion as a promising candidate for the topical management of inflammatory skin conditions. Full article

Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. Magnetic sorting was applied to obtain pure exosomes. Morphology and size were characterized by transmission electron microscopy and nanoparticle tracking analysis. Validation of membrane exosomal markers (CD9, CD63) was performed via Western blotting. MiR-21, miR-31, and miR-133 levels were analyzed in exosomes and parent cells by qPCR. Biological effects of the exosomes were tested by adding them to fibroblast cultures and determining the expression of relevant carcinogenesis markers by qPCR. Exosomes appeared as cup-shaped nano-sized particles, and there was no difference regarding particle diameter and concentration between the three types of exosomes. The oncogenic miR-21 was significantly upregulated both in SCC and SCC-derived exosomes compared to DOK and HaCaT cells and their respective exosomes. However, miR-31 unexpectedly showed the highest expression in normal cells and the lowest in HaCaT exosomes. MiR-133, the tumor suppressor miRNA, was downregulated in both SCC and DOK cells compared to normal (HaCaT) cells, while the opposite situation was observed in exosomes, with HaCaT cells showing the lowest levels of miR-133. The differences in exosome content were reflected in signaling pathway activation in exosome-treated fibroblasts, with SCC exosomes exerting the most potent effect on several cancer-related pathways, notably PIK3/AKT, PTEN, and NOTCH signaling cascades. Full article