Search Results (431)

This study proposes a high-contrast photoacoustic (PA) imaging methodology based on a dual-wavelength confocal metalens, designed to monitor the dissemination of cancer cells and to inform subsequent cancer treatment strategies. The metalens is composed of two metasurfaces that perform filtering and focusing functions, effectively reducing the cross-talk between the two wavelengths of light in space and achieving a confocal effect. Furthermore, to minimize process complexity, a uniform material system of silicon dioxide (SiO₂) and titanium dioxide (TiO₂) is employed across the different metasurfaces of the metalens. The designed metalens has a radius of 25 µm and an operational focal length of 98.5 µm. The results confirm that this dual-metasurface design achieves high focusing efficiency alongside precise focusing capability, with the deviations of the actual focal lengths for both beams from the design values being within 1.5 µm. Additionally, this study developed a skin tissue model and simulated multi-wavelength photoacoustic imaging of cancer cells within the human body by integrating theories of radiative transfer, photothermal conversion, and the wave equation. The results demonstrate that the enhancement trend of the reconstructed signal closely matches the original signal, confirming the model’s excellent fitting performance. The sound pressure values generated by cancer cells are significantly higher than those of normal cells, proving that this method can effectively distinguish cancerous tissue from healthy tissue. This research provides new theoretical support and methodological foundations for the clinical application of multi-wavelength photoacoustic imaging technology. Full article

Historically, clays have been widely used for the treatment of wounds and to stop hemorrhaging. The aim of this study was to combine four natural clay minerals (kaolinite, glauconite, montmorillonite, and bentonite) with magnetite (Fe₃O₄) nanoparticles to produce Fe₃O₄–clay complexes with enhanced antimicrobial properties and chemopreventive activity against melanoma. The magnetite–clay complexes were synthesized by the chemical co-precipitation method and characterized using XRD, TEM, STEM-EDS, SEM, and SQUID magnetometer. Antimicrobial properties were determined by evaluation of MIC values. The most promising materials were also subjected to direct contact antibacterial test according to the OECD standard for porous materials. Cytotoxicity of the complexes towards melanoma cells and normal human skin fibroblasts was assessed by MTT assay. We performed XRD, which confirmed the formation of Fe₃O₄–clay complex materials. It was also proven that complexes exhibited superparamagnetic properties. Microbiological experiments clearly revealed that modification of natural clays with magnetite significantly boosted their antimicrobial properties. Fe₃O₄–montmorillonite and Fe₃O₄–bentonite showed the strongest antimicrobial activity. Moreover, the mentioned complexes had the ability to reduce the viability of melanoma cells by 35–40%, while exhibiting no cytotoxicity against the normal human fibroblast (BJ) cell line, which is an extremely desirable feature. Thus, it may be concluded that Fe₃O₄–montmorillonite and Fe₃O₄–bentonite complexes hold promise for use in the management of infected wounds and wounds after melanoma excision. Full article

Background: Folic acid (FA), also known as vitamin B9, functions as a co-factor in many cellular processes. Ultraviolet radiation (UV) has been shown to cause the formation of free radicals, and chronic exposure of the skin to UV radiation has been demonstrated to result in many adverse effects. Skin protection against harmful environmental factors is one of the aims of cosmetic products. One such substance is folic acid. However, aqueous FA solutions decompose after exposure to UV radiation, and the decomposition products can exhibit variable pro/anti-oxidative roles depending on the cell type and its environment. Objectives: The objective of the present study was to demonstrate the effectiveness of folic acid as a UV-protective agent in vitro cell culture model. Methods: The experimental model comprised an in vitro culture of normal human fibroblasts derived from adult skin (NHDF-Ad). Paramagnetic electron resonance (EPR) was used to assess the interaction of folic acid with free radicals after exposure to UV radiation. RT-qPCR was utilized to evaluate the impact of ultraviolet (UV) radiation on the expression of selected cell cycle regulatory genes (CCND1, P53, BAX, and BCL-2) in vitro cultured fibroblasts that were protected by folic acid. Results: EPR studies revealed the antioxidant properties of folic acid. Free radical forms of folic acid are induced during UV irradiation. The strong effect of UV irradiation on interactions of folic acid with free radicals was observed. The interaction was found to be weaker for the irradiated samples. Molecular studies have demonstrated a decline in the BAX/BCL-2 ratio in cells that have been treated with folic acid and exposed to UV radiation in comparison to the BAX/BCL-2 ratio observed in cells that have been exposed exclusively to UV radiation and not treated with folic acid. Conclusions: Whilst molecular and EPR studies both confirm the effectiveness of folic acid as a UV-protective ingredient in cosmetics and pharmaceutical products, further research in this area is required. Full article

This study presents the development of an advanced three-dimensional (3D) bioprinted skin scaffold integrating sodium alginate (SA), gelatin (Gel), human skin-derived decellularized extracellular matrix (dECM), and microbiota-derived postbiotics. To ensure a biocompatible and functional ECM source, human skin samples collected during elective aesthetic surgical procedures were utilized. Following enzymatic treatment, the dermal layer was carefully separated from the epidermis and subjected to four different decellularization protocols. Among them, Protocol IV emerged as the most suitable, achieving significant DNA removal while maintaining the structural and biochemical integrity of the ECM, as confirmed by Fourier-transform infrared spectroscopy. Building on this optimized dECM-4, microbiota-derived postbiotics from Limosilactobacillus reuteri EIR/Spx-2 were incorporated to further enhance the scaffold’s bioactivity. Hybrid scaffolds were then fabricated using 7% Gel, 2% SA, 1% dECM-4, and 40 mg/mL postbiotics in five-layered grid structures via 3D bioprinting technology. Although this composition resulted in reduced mechanical strength, it exhibited improved hydrophilicity and biodegradability. Moreover, antimicrobial assays demonstrated inhibition zones of 16 mm and 13 mm against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) and Pseudomonas aeruginosa (ATCC 27853), respectively. Importantly, biocompatibility was confirmed through in vitro studies using human keratinocyte (HaCaT) cells, which adhered, proliferated, and maintained normal morphology over a 7-day culture period. Taken together, these findings suggest that the engineered hybrid scaffold provides both regenerative support and antimicrobial protection, making it a strong candidate for clinical applications, particularly in the management of chronic wounds. Full article

A fast-paced lifestyle contributes to heightened emotional stress, driving the demand for milder and safer cosmetic ingredients that can counteract stress-induced skin damage—a focus of cutting-edge research in the field. Aim: The aim was to elucidate the role and mechanistic basis of tea (Camellia sinensis) seed meal saponin (Sap) in regulating stress-induced sebum overproduction and inflammatory responses. Methods: The composition and chemical structure of Sap were analyzed using UV-vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In vitro models of cortisone-induced excessive lipid accumulation and the tumor necrosis factor-alpha (TNF-α)-stimulated inflammatory models were established on sebaceous gland cells (SZ95) and normal human epidermal keratinocytes (NHEKs), respectively. Cortisol and inflammatory cytokine secretion levels in cells were detected using ELISA. Additionally, the signaling pathways were revealed by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-PCR). Results: Five saponins were identified in the Sap extract, all belonging to the oleanolic-acid-type pentacyclic triterpenes. Sap treatment significantly attenuated cortisone-induced cortisol secretion and lipid accumulation in SZ95 sebocytes. Mechanistically, Sap inhibited the 11β-HSD1/SREBP-1 pathway, which mediates its sebosuppressive effects, while concurrently down-regulating the mRNA expression of key downstream transcription factors and enzymes, including SREBP-1, FAS, and ACC. Additionally, Sap treatment significantly attenuated TNF-α-stimulated cortisol secretion and inflammatory cytokine (IL-1β, IL-6, and IL-8) production in NHEK cells through the inhibition of the 11β-HSD1/TLR2/NF-κB signaling pathway. Conclusion: Sap demonstrated dual inhibitory effects, suppressing both emotional-stress-induced sebum overproduction and inflammatory cytokines secretion. Full article

In the present study, we synthesized nine new derivatives of 2-(cyclohexylamino)thiazol-4(5H)-one and evaluated their inhibitory activity against 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 11β-HSD2), an enzyme responsible for the progression of metabolic disorders and cancers. All obtained derivatives showed inhibitory potential against 11β-HSD1, and four of them highly inhibited 11β-HSD1 activity with IC₅₀ values in the low micromolar range. The most active compound, 3h with IC₅₀ = 0.04 µM, became a more potent and selective inhibitor than carbenoxolone. In addition to inhibition of 11β-HSD1, we investigated the antitumor potential and effects on intracellular redox homeostasis of all newly synthesized compounds on five cancer cell lines, namely human colon cancer (Caco-2), human pancreatic cancer (PANC-1), human glioma (U-118 MG), human breast cancer (MDA-MB-231), and skin melanoma (SK-MEL-30) and on healthy fibroblasts derived from the skin of a male neonate (BJ). Among the derivatives, all tested compounds were found to cause a decrease in cell viability for the MDA-MB-231 and Caco-2 lines and for compounds 3b–3i for SK-MEL-30. The redox-modulating activity was assessed by measuring the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), and reduced glutathione (GSH) using the same panel of cancer lines and normal cells. This study showed an increase in ROS levels for SK-MEL-30, Caco-2, and MDA-MB-231 lines, while in the case of GSH levels, its reduction was observed in most experimental sets. The presented data suggest that the tested compounds are promising therapeutic agents with dual action because they offer the possibility of simultaneous regulation of metabolic disorders by inhibiting 11β-HSD1 and play a key role in anticancer therapy, which makes them prospective candidates for further clinical studies. Full article

Tigecycline is an antibiotic belonging to the glycylcycline group of tetracyclines. Similar to other tetracycline derivatives, tigecycline is used in dermatology because of its bacteriostatic effect. Despite an overall favorable safety profile, tetracyclines are associated with a spectrum of cutaneous adverse effects, notably pigmentary disorders and phototoxic reactions. These dermatologic manifestations are presumed to result from tigecycline’s affinity for melanin biopolymer and its subsequent accumulation within the pigment-containing tissues. This study aimed to assess the impact of tigecycline on human normal skin cell homeostasis varied by melanin content. The study was conducted on HEMn-LP melanocytes and human dermal fibroblasts. The aim was achieved by determining the cell number, cell cycle, mitochondrial potential, and redox homeostasis and determining in silico the possibility of binding tigecycline to melanin biopolymers. In this study, it was shown that the cells more sensitive to tigecycline were HEMn-LP melanocytes. The obtained results showed that tigecycline decreased cell number in a dose-dependent manner. In addition, tigecycline was shown to reduce mitochondrial potential, increase the level of oxidized thiols, and increase ROS content in melanocytes, contributing to oxidative stress. In silico studies have shown that the binding of tigecycline to melanin may play a role in the induction of the toxic effects of tigecycline on the skin. Full article

Background/Objectives: This study presents the development and characterization of a novel thermoresponsive hydrogel composed of hyaluronic acid (HA), poloxamer 407, cannabidiol (CBD), and colloidal silver (Ag), designed for topical antimicrobial therapy. Methods: The Ag-CBD complex was first synthesized and subsequently incorporated into a HA–poloxamer gel matrix to produce a stable, sprayable formulation with suitable physicochemical properties for dermal applications. Results: The HA-Ag-CBD hybrid gel exhibited a physiological pH, a gelation temperature compatible with skin surface conditions, and favorable rheological behavior, including thixotropy and shear thinning—critical for uniform application and retention under dynamic conditions. Release studies confirmed a sustained delivery profile, supporting prolonged local activity of CBD and colloidal Ag. Antimicrobial assays demonstrated that the HA-Ag-CBD hybrid gel retained potent activity against Staphylococcus aureus and Candida albicans, with minimum inhibitory and bactericidal concentrations (MIC/MBC) statistically comparable to those of the unencapsulated Ag-CBD complex. Against E. coli, the HA-Ag-CBD hydrogel exhibited primarily bacteriostatic activity, with a low MIC (9.24 μg/mL) but a substantially higher MBC (387.35 μg/mL), consistent with the intrinsic structural resistance of Gram-negative bacteria. In contrast, bactericidal activity was more pronounced against Gram-positive strains, reflecting differential susceptibility related to bacterial envelope properties. CBD consistently demonstrated superior antimicrobial efficacy to colloidal Ag, while the Ag-CBD combination produced slightly enhanced, mainly additive effects, likely due to complementary membrane disruption and intracellular Ag⁺ ion activity. Cytotoxicity assays on normal human dermal fibroblasts confirmed that the HA-Ag-CBD hybrid gel maintained >70% cell viability at therapeutically relevant concentrations, in accordance with ISO 10993-5:2009 guidelines, and effectively mitigated the inherent cytotoxicity of the Ag-CBD complex. Conclusions: The HA-Ag-CBD hybrid gel demonstrates strong potential as a biocompatible, multifunctional topical formulation for the treatment of infected wounds and skin lesions. Future work will focus on in vivo evaluation, assessment of skin permeation, and further development to support translational applications. Full article

The skin protects the body from damaging external stressors. The function of its outermost compartment, the epidermis, depends on high rates of protein synthesis and the production of protective molecules, both requiring amino acids as precursors. Conversely, the degradation of the epidermal barrier protein filaggrin releases free amino acids. Here, we review the epidermal amino acid metabolism, focusing on the metabolism of histidine, arginine and tyrosine, which are subjected to epidermal cell-specific control mechanisms. Histidine and arginine are metabolized by enzymes that are transcriptionally upregulated during terminal differentiation of keratinocytes, while tyrosine is specifically metabolized in melanocytes. Arginase converts arginine into ornithine and urea. While ornithine is decarboxylated to putrescine, a regulator of cellular proliferation, urea contributes to the moisturization of the skin surface. Histidase, also known as histidine ammonia lyase, converts histidine into urocanic acid (UCA) and ammonia. UCA is the main ultraviolet-absorbing molecule of the cornified layer of the epidermis, serving as a natural sunscreen of human skin. In melanocytes, tyrosinase initiates the polymerization of tyrosine to melanin, the main skin pigment that absorbs both visible light and ultraviolet radiation. The current evidence indicates that the metabolism of histidine, arginine, tyrosine and other amino acids critically influences normal and diseased skin. Full article

Mycobacterial spindle cell pseudotumors (MSCPs) are rare lesions characterized by the proliferation of spindle-shaped histiocytes caused by mycobacterial infections. MSCPs have been reported in the lung, lymphatic system, and skin of immunodeficient patients. We present the case of a spindle cell pseudotumor of the pancreas in a 30-year-old male with advanced human immunodeficiency virus (HIV) infection, which led to biliary stricture, splenomegaly, chronic pancreatitis, portal hypertension, compression of the hepatic artery and portal vein, and ascites. This was the patient’s third mycobacterial infection diagnosis. The MSCP was diagnosed via endoscopic biopsy after two prior non-diagnostic biopsies of the pancreatic lesion. Following 18 months of tailored antimycobacterial therapy, the pancreatic mass resolved radiographically with normalization of liver tests and sustained clinical improvement, and there has been no relapse more than 8 months after treatment completion. This case highlights the presentation of an MSCP in a unique anatomic location not previously documented and the challenges encountered with diagnosis and management. Full article

Despite significant medical advancements, two major health challenges persist: antibiotic resistance in microbial pathogens and drug resistance in cancer cells. To address these issues, research has increasingly focused on discovering novel natural compounds with dual antimicrobial and anticancer activities. Among such candidates, antimicrobial peptides (AMPs) have attracted attention due to their ability to selectively target microbial and cancer cells while exhibiting minimal toxicity toward normal cells. Although Vietnam possesses rich biodiversity, including a wide range of Anura species, studies on AMPs from these organisms remain limited. In this study, a novel AMP, brevinin-1 E8.13, was identified from the skin secretion of Sylvirana guentheri, a frog species native to Vietnam. The brevinin-1 E8.13 peptide was successfully cloned, sequenced, and chemically synthesized. Functional assays revealed that brevinin-1 E8.13 possesses strong antibacterial activity against Staphylococcus aureus and exerts significant antiproliferative effects on various human cancer cell lines, including A549 (lung), AGS (gastric), Jurkat (leukemia), HCT116 (colorectal), HL60 (leukemia), and HepG2 (liver). The peptide demonstrated moderate to potent cytotoxic activity, with IC₅₀ values ranging from 7.5 to 14.8 μM, depending on the cell type. Notably, brevinin-1 E8.13 exhibited low cytotoxicity toward normal human dermal fibroblast (HDF) cells and even promoted cell proliferation at lower concentrations. Furthermore, Chemically Activated Fluorescent Expression (CAFLUX) bioassay results confirmed that the peptide significantly downregulated Cyp1a1 gene expression in HepG2 cells. Collectively, these findings highlight the therapeutic potential of brevinin-1 E8.13 as a dual-function antimicrobial and anticancer agent derived from the skin secretion of Sylvirana guentheri. Full article

This study aimed to evaluate the protective effects of Inula japonica leaf extract against PM₁₀-induced oxidative stress in normal human keratinocytes. Keratinocytes were pretreated with various concentrations of Inula japonica leaf extract and subsequently exposed to PM10. Cell viability, ROS production, gene and protein expression (qRT-PCR and Western blot), and UHPLC-MS profiling were assessed. Network pharmacology analysis was conducted using database-predicted compounds of Inulae Flos. The extract significantly reduced PM₁₀-induced ROS generation and restored the expression of epidermal barrier-related genes such as loricrin. It also inhibited phosphorylation of MAPKs (ERK, p38) and modulated apoptotic and inflammatory markers including Bax, p53, MMP-9, and COX-2. UHPLC-MS analysis identified eight compounds not previously reported in our earlier study, which may contribute to the extract’s protective effects. Inula japonica leaf extract exerts protective effects against PM₁₀-induced skin damage by reducing oxidative stress and inflammation in keratinocytes. These findings support its potential as a therapeutic candidate for pollution-related skin disorders. Full article

Two triterpene saponins, hederagenin glucosides, including a novel monodesmoside: 3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin (compound 1), were isolated from the fruits of Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh (Amaranthaceae). These compounds, together with hederagenin itself (compound 4) and a commercially available 28-O-β-D-glucopyranosyl hederagenin ester (compound 3), were evaluated for cytotoxicity and selectivity across a wide panel of human cancer cell lines (skin, prostate, gastrointestinal, thyroid, and lung). All four compounds exhibited dose- and time-dependent effects, with varying potency depending on the specific cancer type. The isolated bidesmosidic saponin (3-O-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin 28-O-β-D-glucopyranosyl ester—compound 2) showed the strongest activity and selectivity, with an IC₅₀ = 6.52 μg/mL after 48 h incubation against WM793 melanoma, and almost no effect on normal HaCaT skin cells (IC₅₀ = 39.94 μg/mL). Multivariate analysis of the obtained data using principal component analysis (PCA) and hierarchical cluster analysis (HCA) supported the assumption that cytotoxicity is influenced by the type of compound, its concentration, and the intrinsic sensitivity of the cell line. Structure-activity observations between closely related hederagenin derivatives are also briefly presented. Full article

Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique phenomenon of melanoma “dormancy” in some animals. To help close this gap in knowledge, melanoma tissue and intact skin collected from gray horses were subjected to transcriptome analysis using RNAseq. In the next step, cultured primary tumor cells and normal skin fibroblasts were established from gray horses, and their protein expression profiles were determined. The obtained data unambiguously identified gray-horse melanoma (ghM) as a malignant tumor, as reflected by the overrepresentation of pathways typically activated in human melanoma and other human cancers. These included the RAS/RAF/MAPK, the IRS/IGF1R, and the PI3K/AKT signaling networks. In addition, the obtained data suggest that the key molecules RAC1, RAS, and BRAF, which are frequently mutated in human melanoma, may also contain activating mutations in ghM, whilst PTEN may harbor loss-of-function mutations. This issue will be subject to downstream analyses determining the mutational status in ghM to further advance the understanding of this frequent disease in gray horses. Full article

Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects highlight the need for novel therapeutic agents. We previously observed that Morus alba extract (MAE) suppressed IL-17-induced CCL20 mRNA expression in normal human epidermal keratinocytes (NHEKs). In this study, we focused on the IL-17 signaling pathway and investigated the effects of pentacyclic triterpenoids, betulinic acid (BA), and ursolic acid (UA), which are present in MAE, on NHEK cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that both BA and UA suppressed CCL20 expression, while only UA alone inhibited CCL20 release. ELISA using specific inhibitors demonstrated that both the p38 and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways were crucial for IL-17-induced CCL20 release in NHEK. UA effectively suppressed ERK1/2 nuclear localization and moderately affected p38 phosphorylation. These results indicated that UA is a potential seed compound for psoriasis treatment through its targeting of the IL-17 pathway. Full article