Search Results (442)

Background/Objectives: Studying the role of UV-induced metabolic changes in skin physiology, and especially skin diseases, has gained importance in both medicine and cosmetics. With the development of new technologies, a variety of approaches have been implemented to model these metabolic effects. In this study, we explore the reproducibility of the UVA1-induced metabolic changes observed in different in vitro, ex vivo, and in vivo systems with escalating complexity. Our aim is to elaborate on the role of experimental setups in the reliable representation of in vivo data in other systems. Methods: Metabolic profiles post UVA1 treatment were assessed in skin cell culture, skin explants, and intact skin. For cell culture and explants, the metabolites from the culture medium were assessed via 1D-CPMG NMR. Intact skin samples were collected via microdialysis and the resulting dialysate was measured with GC–TOF-MS. Results: Data show that, despite great metabolic variations between the systems, several metabolites, such as glutamic acid, succinic acid, and threonine, change in a similar manner across multiple systems after UVA1 irradiation, including in vivo settings. Some metabolites, like phenylalanine, citric acid, and pyruvic acid, show similar UVA-mediated metabolic patterns between corresponding in vitro and ex vivo systems, but do not overlap well with in vivo data. Conclusions: Our findings emphasize the need for a metabolite-by-metabolite approach when deciding on the proper experimental system to perform UV irradiation experiments with regard to cutaneous physiology. Full article

The human skin microbiome has gained considerable attention as a resource for the development of innovative probiotics for cosmetic purposes or promoting skin health. However, the evaluation of new probiotic strains to ensure their “generally recognized as safe” (GRAS) status remains challenging. Here, we have subjected the annotated draft genome sequences of four human skin-derived bacterial strains, namely Bacillus subtilis MBF10-19J, Micrococcus luteus MBF05-19J, Staphylococcus hominis MBF12-19J, and Staphylococcus warneri MBF02-19J, to bioinformatic analyses to detect the genes associated with important probiotic traits, as well as undesirable characteristics such as antibiotic resistance, virulence factors, and toxic metabolites. Each bacterium harbors at least one type of adhesin-encoding gene, while only S. hominis MBF12-19J and S. warneri MBF02-19J contain the putative genes encoding enzymes for metabolism improvement. In vitro assays, including antibiotic susceptibility and antimicrobial activity testing, revealed strain-specific safety characteristics that complement the genomic findings. With regard to antibiotic resistance determinants, S. hominis MBF12-19J showed the most favorable profile, S. warneri MBF02-19J and M. luteus MBF05-19J appeared suitable when used with appropriate caution, and B. subtilis MBF10-19J exhibited amoxicillin resistance, i.e., warrants careful evaluation. Further in vivo validation is needed to determine whether these strains do indeed comply with GRAS evaluation frameworks. Full article

Lignans are naturally occurring compounds found in a wide variety of plant species, including flaxseed, soybean, pumpkin seed, broccoli, sesame seed, and some berries. Lignans have been used for centuries in both food and traditional herbal medicine. Recently, numerous new lignans and lignan derivatives with diverse biological properties have been identified. Lignans are considered promising for human health due to their hydrogen-donating antioxidant activity together with their ability to complex divalent transition metal cations. They have demonstrated beneficial effects for cardiovascular disease, as well as in maintaining blood glucose levels, supporting cardiac health, promoting anti-obesity effects, decreasing the risk of renal diseases, enhancing brain function, improving skin and gut health, among others. This review explores the biosynthesis and biological effects of lignans, with a particular focus on their antihypertensive and anti-obesity properties, as well as the molecular mechanisms involved. It also highlights recent advances in sustainable lignan extraction techniques that are suitable for human use. The mechanisms underlying these bioactivities are thought to involve hormonal metabolism and availability, antioxidant action, modulation of angiogenesis, and more. However, further research is needed to fully elucidate the molecular pathways through which lignans exert their therapeutic effects. Overall, lignans from various plant sources hold significant potential for application in functional foods, dietary supplements, and pharmaceutical products aimed at preventing and managing a range of health conditions, including hypertension and obesity. Full article

Engineered skin (ES) can serve as an advanced therapy for treatment of large full-thickness wounds, but delayed vascularization can cause ischemia, necrosis, and graft failure. To accelerate ES vascularization, this study assessed incorporation of polydopamine (PDA) microparticles loaded with different concentrations of basic fibroblast growth factor (bFGF) into collagen scaffolds, which were subsequently seeded with human fibroblasts to create dermal templates (DTs), and then keratinocytes to create ES. DTs and ES were evaluated in vitro and following grafting to full-thickness wounds in immunodeficient mice. In vitro, metabolic activity of DTs was enhanced with PDA+bFGF, though this increase was not observed following seeding with keratinocytes to generate ES. After grafting, ES with bFGF-loaded PDA microparticles displayed dose-dependent increases in CD31-positive vessel formation vs. PDA-only controls (p < 0.001 at day 7; p < 0.05 at day 14). Interestingly, ES containing PDA+bFGF microparticles exhibited an almost 3-fold increase in water loss through the skin and a less-organized basal keratinocyte layer at day 14 post-grafting vs. controls. This was associated with significantly increased inflammatory cell infiltrate vs. controls at day 7 in vivo (p < 0.001). The results demonstrate that PDA microparticles are a viable method for delivery of growth factors in ES. However, further investigation of bFGF concentrations, and/or investigation of alternative growth factors, will be required to promote vascularization while reducing inflammation and maintaining epidermal health. Full article

Opophytum forskahlii has a well-established ethnopharmacological significance. This study aimed to assess the skin anti-aging and hair growth-promoting activities of O. forskahlii seed oil (OFSO) and the underlying mechanism. GC-MS profiling revealed high levels of unsaturated fatty acids, linoleic acid (55.46%), and oleic acid (38.54%). The skin anti-aging activity of OFSO (3.125–100 µg/mL) was evaluated in normal human dermal fibroblasts (NHDFs) using MTT and enzyme inhibition assays. OFSO was non-cytotoxic and enhanced fibroblast proliferation in a dose-dependent manner, reaching 145.5% of control at 100 µg/mL (p < 0.05). OFSO significantly (p < 0.05) inhibited collagenase (48%), hyaluronidase (53%), elastase (57%), and tyrosinase (55%). The oil showed anti-inflammatory activity by inhibiting COX-1 and COX-2 (0.01–100 µg/mL) with IC₅₀ = 0.125 and 0.014 µg/mL, respectively. The hair growth promoting efficacy was assessed using adult male Wistar rats, randomly divided into control, OFSO-treated, and 2% minoxidil-treated groups (5 rats/group). Hair growth was assessed through visual scoring over 14 days of topical application and confirmed by histological examination and hair follicle counting. On day 14, the OFSO-treated group displayed almost complete hair coverage (score about 5.0), exceeding minoxidil (about 4.0), and significantly increased hair follicle number (14.0 ± 1 vs. 9.2 ± 0.8, p < 0.05). Histology confirmed that OFSO promoted hair follicle growth, differentiation, and transition from the telogen to the anagen phase. Network pharmacology analysis, integrating targets predicted via SwissTargetPrediction and disease-associated genes from GeneCards, identified PPARG, ESR1, and IL6 as key hub genes underlying OFSO’s effects. PPARG enhances antioxidant defenses, anti-inflammatory responses, and sebaceous gland function; ESR1 supports collagen production, skin elasticity, and follicle vascularization; and IL6 modulates inflammation and triggers the anagen phase of hair growth. Functional enrichment revealed modulation of PPAR, estrogen, prolactin, and arachidonic acid metabolism pathways, suggesting that OFSO may regulate lipid metabolism, inflammation, hormonal signaling, and tissue regeneration. OFSO demonstrated promising anti-aging and hair growth activities, supporting further development and testing of cosmetic formulations. Full article

This review elucidates the foundational principles of nicotinamide adenine dinucleotide (NAD⁺) homeostasis in humans, emphasizing its depletion during aging and in age-associated disorders. Subsequently, the discussion extends to NAD⁺ precursors and their potential therapeutic applications, with insights from research using zebrafish as a disease model. This information sheds light on the growing interest in NAD and its metabolism in the medical field and sparks curiosity among researchers focused on fish studies. The review further explores the role of nicotinamide in fish, encompassing core NAD⁺ metabolism, its participation in oxidative stress, environmental challenges, and the mitigation of pollutant-induced toxicity. Additionally, the implications of NAD⁺ in fish neurobiology, immune regulation, host–pathogen interactions, skin, eggs, and post mortem muscle were considered. Dietary modulation of NAD⁺ pathways to enhance growth, immunity, and product quality in aquaculture has also been highlighted. This review highlights the significance of NAD⁺ metabolism in fish biology, covering cellular energy production, physiological processes, and environmental adaptation, and proposes targeting NAD⁺-related pathways as a strategy for aquaculture and fish health management. Full article

Haloarchaea are moderate and extreme halophilic microorganisms inhabiting hypersaline environments characterised by high ionic and oxidative stress due to extremely high salt concentrations and high incidence of UV radiation (mainly in spring and summer). To be alive and metabolically active under these harsh conditions, haloarchaeal strains have developed molecular adaptations, like hyperpigmentation. Among the carotenoids produced by haloarchaeal species, the C₅₀ carotenoid called bacterioruberin (BR) and its derivatives, monoanhydrobacterioruberin and bisanhydrobacterioruberin, are the predominant natural pigments produced. This review aims to highlight the most significant characteristics of BR and their derivatives, as well as a description of the biological activities already reported that could provide benefits for human health, including antitumoral, immunomodulatory, antioxidant, skin protectant, antilipidemic, antiglycemic, and anti-atrophic effects, in addition to showing potential positive effects on sperm cells cryopreservation. Overall, C₅₀ carotenoids are fascinating natural biomolecules that could be utilised in processed food and nutraceuticals or as tools in the context of new strategies and/or pharmaceutical formulations to combat various human diseases or metabolic disorders. Full article

Chronic low-grade inflammation and oxidative stress induced by the exposome represent key drivers of skin aging and related imperfections. The development of experimental models suitable for studying these metabolic processes is therefore of primary importance for the cosmetic industry. In recent years, the role of specialized pro-resolving mediators (SPMs) in the resolution of inflammation has been highlighted; however, in vitro skin models to investigate them are still lacking. In this work, we developed an ex vivo human skin culture model that allows the quantification of maresin 1 (MaR1) production by measuring its concentration in the conditioned culture medium using an ELISA-based assay. The presence and survival of MaR1-synthesizing immune cells, namely Langerhans cells and leukocytes, were quantified during the first days of culture. The model’s ability to modulate MaR1 production was assessed in response to treatment with its precursor, docosahexaenoic acid (DHA), and with a DHA-rich cosmetic ingredient named Isochrysis Galbana Extract. Results demonstrated that the model produces MaR1 even in the absence of stimulation and responds to treatments with a further increase in MaR1 production. Furthermore, the tissue-to-medium ratio required to obtain MaR1 concentrations suitable for effective ELISA quantification was optimized. This model establishes a reproducible and scalable experimental platform for quantifying SPMs and evaluating DHA-based formulations, supporting both cosmetic research and mechanistic investigations. Full article

Polyethylene terephthalate-derived fluorescent carbon quantum dots (PET-CQDs) are promising nanomaterials for sensing and biomedical uses, yet their biological interactions after metal doping require careful evaluation. Here, we report an in silico assessment of pristine and dual-site (via graphitic [G] and carbonyl [O]) metal-doped PET-CQDs (Ca, Mg, Fe, Zn) using molecular docking against eight human proteins: HSA (distribution), CYP3A4 (metabolism), hemoglobin (systemic biocompatibility), transferrin (uptake), GST (detoxification), ERα (endocrine regulation), IL-6 (inflammation), and caspase-3 (cytotoxic signaling) together with ADMET profiling and DFT–docking correlation analysis. Docking affinities were compared with controls and ranged from −7.8 to −10.4 kcal·mol⁻¹ across systems, with binding stabilized by π–π stacking, hydrogen bonding and metal–ligand coordination involving residues such as arginine, tyrosine and serine. Importantly, top-performing CQD variants differed by target: PET-CQDs, MgG_PET-CQDs and FeG_PET-CQDs were best for GST; ERα interacted favorably with all doped variants; IL-6 bound best to CaO_PET-CQDs and FeO_PET-CQDs (≈−7.1 kcal·mol⁻¹); HSA favored CaG_PET-CQDs (−10.0 kcal·mol⁻¹) and FeO_PET-CQDs (−9.9 kcal·mol⁻¹); CYP3A4 bound most strongly to pristine PET-CQDs; hemoglobin favored MgG_PET-CQDs (−9.6 kcal·mol⁻¹) and FeO_PET-CQDs (−9.3 kcal·mol⁻¹); transferrin favored FeG_PET-CQDs; caspase-3 showed favored binding overall (pristine −6.8 kcal·mol⁻¹; doped −7.4 to −7.6 kcal·mol⁻¹). ADMET predictions indicated high GI absorption, improved aqueous solubility for some dopants (~18.6 mg·mL⁻¹ for Ca-O/Mg-O), low skin permeability and no mutagenic/carcinogenic flags. Regression analysis showed frontier orbital descriptors (HOMO/LUMO) partially explain selective affinities for ERα and IL-6. These results support a target-guided selection of PET-CQDs for biomedical applications, and they call for experimental validation of selected dopant–target pairs. Full article

Chronic inflammatory skin diseases and neurodegenerative disorders share overlapping genetic, immunologic, and metabolic pathways that may predispose individuals to cognitive decline. This review synthesizes current human genomic, transcriptomic, and bioinformatic evidence linking psoriasis, rosacea, atopic dermatitis, and bullous pemphigoid with Alzheimer’s and Parkinson’s disease. Literature from PubMed, IEEE Xplore, and Google Scholar was examined, prioritizing studies integrating genomic, transcriptomic, and proteomic analyses. Among inflammatory dermatoses, psoriasis exhibits the strongest overlap with dementia genetics, with shared susceptibility loci including APOE, IL12B, and HLA-DRB5, and transcriptional regulators such as ZNF384 that converge on IL-17/TNF signaling. Rare-variant and pleiotropy analyses further implicate SETD1A and BC070367 in psoriasis–Parkinson’s comorbidity. Rosacea demonstrates upregulation of neurodegeneration-related proteins SNCA, GSK3B, and HSPA8, together with shared regulatory hubs (PPARG, STAT4, RORA) driving NF-κB/IL-17/TNF-dependent inflammation. In atopic dermatitis, rare FLG variants interacting with BACE1 suggest a mechanistic bridge between barrier dysfunction and amyloidogenic processing. Bullous pemphigoid reveals an HLA-DQB1*03:01-mediated immunogenetic link hypothesis and cross-reactive autoantibodies targeting BP180 (collagen XVII) and BP230, highlighting an autoimmune route of neurocutaneous interaction. Other inflammatory and neurodegenerative diseases with currently weak or limited genetic evidence are also discussed, as they may represent emerging biological pathways or potential therapeutic targets within the skin–brain connection in the future. The aim of this work is to help clarify these genetic links and to advocate for the routine cognitive assessment of affected patients, enabling early detection, improved long-term quality of life, and the potential for timely therapeutic intervention. Full article

A novel bacterial strain, Lysinibacillus sp. JNUCC 51, was isolated from volcanic soil collected at Baengnokdam Crater Lake, Mt. Halla, Jeju Island, Republic of Korea. Phylogenetic, ANI (88.76%), and dDDH (70.4%) analyses indicated that the strain represents a distinct genomic lineage closely related to L. xylanilyticus. The complete genome (5.12 Mb; 37% G+C) encoded 4912 genes, including ten biosynthetic gene clusters (NRPS, β-lactone, RiPP, terpene, and T3PKS types), suggesting strong metabolic versatility. Cells were Gram-positive rods (1.5–3.0 × 0.5–0.7 µm) growing at pH 4.0–9.0 and up to 5% NaCl. Chemotaxonomic profiles revealed iso-C₁₅:₀, iso-C₁₇:₀, and iso-C₁₆:₀ as dominant fatty acids; MK-6/MK-7 as major quinones; and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and phosphatidylcholine as main polar lipids. Bioactivity-guided fractionation of the culture extract led to the isolation of Diolmycin A2 (phenolic polyketide) and maculosin (diketopiperazine), both exhibiting anti-inflammatory and melanogenesis-inhibitory effects consistent with their PKS/NRPS gene clusters. The culture broth suppressed nitric oxide production in LPS-stimulated RAW 264.7 macrophages and reduced melanin synthesis in α-MSH–induced B16F10 melanocytes. A human patch test (5% extract) confirmed dermatological safety. Overall, Lysinibacillus sp. JNUCC 51 is a volcanic-origin bacterium producing structurally diverse bioactive metabolites with promising postbiotic and cosmeceutical potential, particularly for skin inflammation and pigmentation control. Full article

Objectives: Pseudomonas aeruginosa is an opportunistic pathogen of high clinical relevance due to its ability to form biofilms, its inherent virulence regulated by quorum-sensing systems, and its multidrug resistance. In the present study, we evaluated the inhibitory potential of nine extracts from Inula species (chloroform and methanolic fractions, including a sesquiterpene lactone-enriched fraction) against biofilm formation and virulence-associated traits of P. aeruginosa PAO1 and three multidrug-resistant clinical isolates, as well as their cytotoxicity, biocompatibility, and ability to affect cytokine and nitric oxide production in infected skin explants. Methods: The following methods were applied: fractionation and extraction of plant extracts; cytotoxicity assessment on HFF cells; crystal violet assay for determining antibiofilm activity; fluorescence microscopy for evaluating biofilm viability; electron microscopy for assessing the 3D structure of biofilms and morphological alterations; inhibition assays of pyocyanin pigment, protease activity, bacterial motility, interleukin-17, and nitric oxide production; histological analysis of mouse skin explants. Results: Quantitative analyses of antibiofilm activity revealed that five of the tested extracts inhibited biofilm formation by more than 50%. Structural and functional analyses using confocal laser scanning microscopy and scanning electron microscopy demonstrated a substantial reduction in biofilm thickness, exfoliation of biofilm biomass, the presence of isolated bacterial clusters, metabolically inactive cell populations, and morphological abnormalities associated with cell elongation, invaginations, and polar deformations as a consequence of treatment. In addition, the plant extracts strongly affected virulence factors regulated by quorum sensing. The methanolic fractions from I. britannica and I. bifrons significantly suppressed pyocyanin synthesis. In contrast, the chloroform fractions from I. helenium and I. spiraeifolia produced the largest inhibition zones in assays for extracellular protease activity. Furthermore, all chloroform extracts suppressed bacterial motility, with the lowest swarming diameter observed for the chloroform and lactone-enriched fractions from I. britannica. The chloroform extracts of I. helenium and I. bifrons, methanolic extracts of I. britannica, and chloroform and methanolic extracts of I. spiraeifolia showed relatively low toxicity to normal diploid human fibroblasts. Methanolic and chloroform fractions from I. britannica disrupted biofilm integrity and reduced IL-17A and nitric oxide production in infected skin explants. Conclusions: All these findings indicate a possible synergistic action of the chemical constituents within the fractions on quorum-sensing regulation, biofilm formation, cellular viability, and modulation of host inflammatory responses. Full article

Thyrostimulin is a heterodimeric glycoprotein hormone composed of two subunits, GPA2 and GPB5, first identified in 2002. It is considered an ancestral member of the glycoprotein hormone family and is highly conserved across species, including vertebrates and invertebrates. Unlike classical pituitary glycoprotein hormones such as TSH, LH, and FSH, thyrostimulin appears to function predominantly through paracrine and autocrine mechanisms, with its expression reported in diverse tissues such as the pituitary, ovary, skin, and brain. In humans, thyrostimulin has been implicated in ovarian cancer cell proliferation, stem cell quiescence in the pituitary, and metabolic regulation. However, its role in metabolism remains unclear, with studies showing both beneficial and adverse effects such as weight loss in some models and elevated levels in polycystic ovary syndrome and metabolic syndrome patients. In Caenorhabditis elegans, orthologs of GPA2 and GPB5 have been shown to influence growth and intestinal function via a neuroendocrine pathway involving thyrotropin hormone-like peptides. These findings suggest that thyrostimulin has conserved multifunctional roles in development, metabolism, and endocrine signaling. The aim of this review is to summarize the structure–function relationships and the currently known roles of thyrostimulin and its subunits, GPA2/GPB5, particularly in the reproductive system, metabolic syndrome, skeletal development, and obesity. Full article

UVB radiation present in sunlight is the main pro-oxidative and pro-inflammatory factor that reaches human skin cells, including keratinocytes. Therefore, protective compounds eliminating the negative impact of UVB radiation are constantly being sought. This study aimed to estimate the effect of the lipid extract of microalgae Nannochloropsis oceanica (N.o.) on UVB-irradiated keratinocytes. A proteomic approach was used to estimate the proteomic profile of in vitro-treated keratinocytes. The results indicated 270 proteins had significantly altered expression in UVB-irradiated keratinocytes, while the treatment of cells with N.o. extract partially restored the levels of these proteins. Moreover, changes in protein structure resulting from the binding of glutathione (GSH) and thioredoxin (Trx) were also observed. Most of the GSH-modified proteins were involved in GSH or prostaglandin metabolism, while Trx-modified proteins were molecules related to Trx metabolism, as well as antioxidant and anti-inflammatory signaling. The treatment of cells with N.o. extract contributed to reversing the changes in the level of modification in individual proteins. It can be suggested that the lipid components of the microalgae N.o. extract protect keratinocytes against changes in metabolism induced by UVB radiation, modulating the antioxidant and pro-inflammatory responses of cells at the GSH and Trx-based signaling levels. Full article

Rosacea is a chronic inflammatory skin disorder of multifactorial pathogenesis, in which dysregulated innate immunity, neurovascular dysfunction, oxidative stress, and microbiome imbalance are central contributors. Recent molecular studies have revealed altered cytokine expression (e.g., IL-1β, IL-6, IL-36 family), aberrant activation of signaling pathways (STAT3, NF-κB, MAPKs), and enhanced expression of innate immune receptors such as TLR2,b TLR4, and TLR7, all of which promote chronic inflammation, angiogenesis, and barrier dysfunction. This systematic review was performed according to PRISMA guidelines. A total of 1425 records were retrieved from PubMed, Scopus, and Web of Science, and 14 studies met the inclusion criteria. The included studies comprised both clinical cohorts and translational experimental investigations using human samples. Reported findings consistently confirmed systemic and tissue-specific inflammatory activity, with elevated circulating monocytes, indoleamine 2,3-dioxygenase, and inflammatory indices, as well as tissue expression of STAT3, NF-κB, MAPKs, and cathelicidin fragments. Oxidative stress markers (TOS, OSI, AOPP, MMP-9) and hypoxia-related molecules (HIF-1α) were significantly increased in patients, correlating with disease severity and vascular manifestations. Taken together, these results highlight that rosacea involves both cutaneous and systemic molecular alterations. The evidence identifies multiple biomarkers with diagnostic potential and provides mechanistic insights into immune, vascular, and metabolic dysregulation. Future research should aim to validate these findings in larger cohorts, establish standardized biomarker panels, and explore novel therapeutic strategies targeting key molecular pathways. Full article