Search Results (11,356)

Background/Objectives: The aim of the present study was to conduct a systematic in vitro assessment of the biofunctionalities of newly synthesized lignin (LNPs) and lignin–chitosan nanoparticles (LCNPs) via a comparative in vitro estimation of their cytotoxicity, cytocompatability potential, radical-scavenging activity, and antimicrobial performance, thereby establishing a benchmark for their sustainable design and biomedical applications. Methods: LNPs and LCNPs were synthesized via “green” self-assembly and co-assembly methods. Results: In vitro cytotoxicity studies on L929 fibroblasts and HaCaT keratinocytes demonstrated higher long-term viability for LCNPs (half-maximal inhibitory concentration IC₅₀ = 3.05 mg/mL at 72 h) compared with LNPs (IC₅₀ = 1.37 mg/mL), while both formulations maintained >76% viability at a concentration of 0.5 mg/mL. Electron Paramagnetic Resonance (EPR) and spectrophotometric antioxidant assays displayed strong radical scavenging activity, with LNPs excelling in ^●OH, NO, and ABTS scavenging and LCNPs exhibiting enhanced lipid peroxidation and superoxide inhibition potential. Antimicrobial testing revealed minimal inhibitory concentration (MIC) reductions of the nanoparticles up to 8–13-fold compared to lignin solutions, with LCNPs showing higher activity against Gram-positive and Gram-negative microbial strains. Conclusions: These results highlight LCNPs as biocompatible, antioxidant, and antimicrobial nanoplatforms with potential for regenerative medicine, oxidative stress mitigation, and infection control. Full article

DNA polymerase beta (Polβ) is a 39 kDa, single polypeptide enzyme that possesses both gap tailoring and nucleotidyl transferase activity and is the key polymerase involved in base excision repair (BER) and the final steps of active gene demethylation. We demonstrated that residues in the mouse Polβ protein, L301 and V303, are critical for Polβ’s interaction with the BER scaffolding protein X-ray repair cross-complementing 1 (XRCC1), and mutation of these residues impairs Polβ’s ability to bind to XRCC1, negatively impacting BER complex assembly. We developed Polβ^{L301R-V303R/L301R-V303R} knock-in mice to explore how defects with this essential protein complex impact genome stability in the mouse. We found these mice to be viable and fertile yet exhibited a modest reduction in body weight. Here, we examined the protein and mRNA levels in tissues from wild-type (WT), heterozygous (HET), and homozygous (HOM) Polβ^{L301R-V303R/L301R-V303R} mice and the derived fibroblast cell lines. We show that HOM mice have significantly diminished Polβ protein levels, as compared to WT mice, in several tissues, yet Polβ mRNA levels were not significantly different, suggesting the decreased levels of Polβ protein could not be attributed to lower gene expression. Upon examination of Polβ stability in mouse ear fibroblasts derived from WT and HOM mice, results are consistent with human cell studies that the Polβ^L301R-V303R protein is unstable and undergoes proteasome-mediated degradation. Finally, we evaluated WT, and HOM, liver and brain genomic DNA samples for 5-methylcytosine/5-hydroxymethylcytosine (5mC/5hmC) levels by nanopore sequencing to investigate the impact of suppressed Polβ protein levels on active gene demethylation. As expected, we found tissue-specific trends in methylation, when comparing the brain and liver. However, we were unable to discern substantial differences in methylation levels between WT and HOM mice, suggesting that in the absence of external stressors, low Polβ levels do not impact methylation patterns. Full article

Currently, there is no curative medication for idiopathic pulmonary fibrosis (IPF), and therapeutic interventions for IPF are hindered by limited efficacy and severe adverse side effects. Far Infrared Radiation (FIR), an invisible form of electromagnetic energy, has garnered increasing attention for its multiple biological effects. However, its therapeutic benefits and the underlying mechanisms of IPF have not been investigated. In the present study, we established a mouse model of bleomycin-induced pulmonary fibrosis (BIPF) to assess the efficacy of FIR in attenuating BIPF. The results showed that FIR therapy significantly improved the general condition of the mice and protected pulmonary function by ameliorating lung fibrosis, collagen deposition and excessive inflammation. Moreover, FIR could alleviate fibroblast-to-myofibroblast differentiation (FMD), the epithelial–mesenchymal transition (EMT) and angiogenesis in BIPF mice. These beneficial effects were notable both in the pro-fibrotic inflammatory stage and the following fibrotic stage. Mechanistically, FIR exerted anti-inflammatory and anti-fibrotic effects through modulating the p53/TGF-β signaling pathway. Overall, this study elucidates the anti-fibrotic activity and the potential molecular mechanisms of FIR in treating BIPF, providing a therapeutic strategy of convenient, non-invasive physical therapy for alleviating IPF. Of greater significance, the findings of this study display the promising future applications of FIR in managing the physiopathology of various chronic diseases. Full article

Brucella infection is frequently acquired by inhalation, but the pathogen disseminates systemically from the lungs. However, little is known about the interaction of Brucella spp. with the airways. Using a 3D air-exposed organotypic human bronchial tissue model (polarized 16HBE14o- bronchial epithelial cells grown over a collagen matrix containing MRC-5 lung fibroblasts), we analyzed Brucella abortus replication, translocation and cytokine responses over prolonged post-infection times. Apically inoculated B. abortus invaded, replicated and persisted during the whole follow-up (16 days) within the bronchial tissue without inducing cytotoxicity. Viable bacteria were also detected in the conditioned medium (CM) since day five post-infection, indicating release from the basolateral side. In parallel experiments, no invasion or bacterial release was detected for Escherichia coli. The levels of IL-6, IL-8 and MCP-1 were increased in CM from Brucella-infected 3D cultures and in monocultures of polarized bronchial epithelial cells or lung fibroblasts. Collagenase/gelatinase activity was increased in 3D cultures and MRC-5 monocultures. Infection transference from bronchial cells to lung fibroblasts was documented using monocultures. An immune cross-talk was detected, as cytokine levels were increased in fibroblasts stimulated with bronchial CM, and vice versa. These results suggest that the bronchial mucosa can sustain B. abortus persistence, replication and dissemination, and that it induces a proinflammatory response to which both epithelial cells and fibroblasts contribute. Full article

Ensuring efficient nutrient delivery and waste removal within the interior of three-dimensional (3D) cultures remains a major challenge in tissue engineering. Here, we demonstrate a proof-of-concept methodology that creates internally distributed driving sources to enhance diffusion and perfusion within 3D constructs. Iron microparticles or iron-containing microtubes were incorporated into collagen gels used for the 3D culture of dermal or cardiac fibroblasts, and cyclic dynamic magnetic fields were applied to the constructs. Oscillatory motion of the iron particles enhanced diffusion within the gels, as evidenced by increases in the fast diffusion coefficient of more than threefold and the slow diffusion coefficient of more than tenfold under conditions suitable for cell culture. In cardiac fibroblast cultures, this enhancement significantly increased proliferation by approximately twofold and reduced cytotoxicity by half compared with controls. In contrast, no significant effects were observed in dermal fibroblast cultures. Cyclic compression of microtubes within the collagen gels induced by dynamic magnetic fields primarily resulted in cellular morphological changes, including a reduction in cell area to approximately 0.8-fold of the control values, increased cell polarization with the cellular aspect ratio rising from 1.4 to 1.9, and preferred cell orientations either parallel or perpendicular to the microtube axis. Together, these results suggest that this methodology has the potential to be developed as an effective strategy for improving diffusivity in 3D metabolic environments and for promoting angiogenesis in hydrogel-based cultures. Full article

The aim of the study was to define radiobiological effects of single and fractionated low doses in normal fibroblasts in 40 patients with squamous cell carcinoma of the head and neck (HNSCC) treated with induction chemotherapy combined with low-dose fractionated radiation (LDFR) and to answer the question regarding the role of low-dose hyper-radiosensitivity (HRS) in these effects. HRS status was determined using flow cytometry-based clonogenic survival assay (cells were irradiated with doses 0.1–4 Gy of 6 MV X-rays). Radiobiological effects (cell kill, kinetics of DSB recognition and repair, chemopotentiation) of LDFR 4x0.5 Gy and a single dose of 2, 0.5 and 0.2 Gy were estimated by clonogenic, pATM and γH2AX foci assays. HRS response was demonstrated for normal fibroblasts in 6 of the 40 HNSCC patients. For all assessed biological parameters, significant interindividual differences were observed. The presence of HRS had no effect on the chemopotentiating effects of LDFR 4x0.5 Gy, which were similar to that after 2 Gy. There was also no association between HRS and the maximum number of pATM and γH2AX foci induced by single (0.2, 0.5, 2 Gy) or fractionated low doses 4x0.5 Gy. Significantly higher percentages of residual pATM and γH2AX foci observed after LDFR 4x0.5 Gy than after 2 Gy were independent of HRS. HRS is a rare finding (15%) in normal fibroblasts from HNSCC patients; therefore, it is of rather little importance in healthy late-reacting connective tissues. Moreover, the fibroblast response to single and fractionated low doses (alone or in combination with carboplatin and paclitaxel) appeared more dependent on individual radiosensitivity than on HRS. Full article

Thin, dry skin is characterized by impaired barrier integrity, loss of dermal density, and accelerated aging driven by intrinsic and extrinsic factors. Biomimetic collagen peptides mimic native collagen sequences, stimulating fibroblasts to enhance synthesis while limiting matrix metalloproteinase-mediated degradation. This study evaluated the clinical efficacy and safety of a multi-ingredient cosmetic product for thin, dry, aging skin, formulated as a dual-purpose body and face serum lotion containing 0.1% biomimetic collagen tripeptide (Tripeptide-29) along with Niacinamide, Citrullus lanatus fruit extract, and Selaginella lepidophylla extract. In this prospective, single-center study, 47 healthy women, aged 36–65 years with Fitzpatrick skin types I–IV, applied the formula twice daily to the face and body over four weeks. Objective measurements—including elasticity, wrinkle depth and volume, hydration, trans-epidermal water loss (TEWL), and texture—were collected weekly alongside clinical grading and self-assessments. Significant improvements were observed across all parameters, with facial dryness decreasing immediately (−74.6%) and continuing to week 4 (−93.7%), hydration increasing up to 72.5%, softness improving up to 37.7%, roughness decreasing up to 37.9%, and TEWL reductions indicating strengthened barrier function. Desquamation improved by 75.5% by week 3, and no adverse effects occurred. The serum lotion demonstrated robust, well-tolerated benefits for enhancing multiple markers of thin, dry, aging skin. Full article

Background: Abnormal activation of the NRF2-cGAS-STING-NF-κB pathway can trigger an inflammatory cascade in rheumatoid arthritis (RA). Curcumin (CUR), a polyphenolic compound extracted from turmeric, possesses anti-inflammatory activity, but whether it can modulate this pathway to ameliorate RA remains unclear. This study aims to elucidate whether CUR inhibits the inflammatory response in synovial fibroblasts (MH7A) by suppressing the NRF2-cGAS-STING-NF-κB signaling cascade. Methods: An RA inflammatory model was constructed by stimulating MH7A cells with 20 ng/mL tumor necrosis factor (TNF). Groups included a control group, a model group, a methotrexate positive control group [MTX(methotrexate), 10 μmol/L], and curcumin treatment groups at varying concentrations (10–100 μmol/L). Cell viability was assessed using the CCK-8(Cell Counting Kit-8) assay. Cell migration and invasion capabilities were evaluated via scratch wound healing and Transwell assays, respectively. Apoptosis was detected by flow cytometry. mRNA and protein expression levels of NRF2(Nuclear factor erythroid 2-related factor 2), cGAS(cyclic GMP-AMP synthase), STING(stimulator of interferon genes), and NF-κB(nuclear factor kappa-light-chain-enhancer of activated B cells) were measured using qRT-PCR and Western blot, respectively. Protein localization was determined by immunofluorescence. Results: Compared to the model group (TNF-induced), the cell migration rate in the curcumin (CUR) groups was significantly decreased (p < 0.001), with a particularly marked reduction observed at a concentration of 50 μmol/L. Furthermore, as the concentration of curcumin increased, cell invasion capacity showed a significant dose-dependent decline. The apoptosis rate also significantly decreased with increasing curcumin concentrations, demonstrating a clear concentration-dependent effect. Mechanistically, curcumin treatment significantly upregulated the expression of NRF2 and inhibited the activation of its downstream cGAS-STING-NF-κB signaling pathway. Specifically, both mRNA and protein expression levels of NRF2 were markedly elevated (p < 0.001), while the mRNA and protein levels of cGAS, STING, and NF-κB were all significantly reduced (p < 0.001). Conclusions: Curcumin (CUR) can effectively inhibit the inflammatory response of synovial fibroblasts by activating the expression of NRF2 and subsequently suppressing the cGAS-STING-NF-κB signaling pathway. This study provides a new molecular mechanism target for curcumin in the treatment of RA and offers a theoretical basis for the intervention of autoimmune diseases with natural products. Full article

Cell-free protein synthesis has become a powerful tool for producing functional proteins, circumventing many limitations of live-cell systems. Platforms based on wheat germ extract are favored for their high efficiency in translating and folding complex eukaryotic proteins. To overcome the energy limitation common in such systems, we engineered an Escherichia coli strain to function as a self-renewing ATP source. This strain co-expresses a three-enzyme cascade—adenosine kinase, adenylate kinase, and acetate kinase—that efficiently converts adenosine and acetyl phosphate into ATP. Using the lysate from this biocatalyst to energize an optimized wheat germ extract, we established a high-performance cell-free synthesis platform. This integrated system supported the robust production of multiple recombinant proteins. As a key demonstration, we synthesized human vascular endothelial growth factor 165, which exhibited full biological activity. The cell-free-produced VEGF₁₆₅ significantly stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs). It also potently induced angiogenic responses, including the formation of extensive, interconnected capillary-like networks by HUVECs in vitro and accelerated cell migration in scratch-wound assays. Our work establishes a scalable and efficient platform for on-demand production of bioactive eukaryotic proteins, highlighting its considerable potential for advancing regenerative medicine and related therapeutic applications. Full article

Zirconium is a widely used material in the field of dentistry, employed for implants and their components as well as for the creation of crowns and veneers. Given that its biocompatibility has been studied and demonstrated in various fields of application, it is necessary to analyze how surface modification of this material influences its properties. The purpose of this study was to analyze the biocompatibility, initial adhesion (48 h), and morphology of periodontal ligament stem cells (PDLSCs) seeded on different zirconium surfaces treated with laser micropatterning, as well as plastic coverslips as a control. The Neubauer chamber was used to count the cells adhered to each of the sets, and confocal and scanning electron microscopy were employed to examine the adhesion and morphology of periodontal ligament stem cells on each of the zirconium surfaces studied. Results: Statistically significant differences were found in terms of primary cell adhesion, with sets 3 (grid topography) and 4 (channel topography) showing the most favorable characteristics for fibroblast adhesion. It was concluded that regular and moderately rough surfaces promoted better cell proliferation and development. Full article

Background/Objectives: Current clinical evidence suggests that cannabidiol (CBD) demonstrates therapeutic potential in the management of chronic pain, particularly in conditions involving inflammation. However, its therapeutic potential is severely limited by poor oral bioavailability, extensive first-pass metabolism, and the need for frequent high-dose administration, which compromises patient adherence and tolerability. Long-acting injectable (LAI) delivery systems offer a strategy to overcome these limitations by providing sustained plasma concentrations and reducing dosing frequency. This study aimed to develop and optimise CBD-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for LAI delivery and to evaluate poly(2-ethyl-2-oxazoline) (POx) as a functional and biocompatible alternative to the conventionally used poly (ethylene glycol) (PEG). Methods: CBD-loaded microspheres were prepared using emulsion–solvent evaporation technique. The formulations were optimised based on entrapment efficiency (EE), drug loading (DL), particle size distribution, surface morphology, thermal behaviour, in vitro release kinetics, and cytocompatibility using NIH 3T3 fibroblasts. Multiple in vitro release methodologies, including dialysis bag, shaking-flask, and USP Apparatus IV, were evaluated to identify the most discriminative and practical approach for long-term release assessment. Results: The optimised POx-based microspheres demonstrated superior control over particle size, yielding significantly smaller and more uniform particles compared with PEG-based microspheres (124 ± 1.47 µm vs. 218 ± 13.5 µm, respectively). Differential scanning calorimetry (DSC) confirmed molecular dispersion of CBD within the polymer matrix. In vitro release studies demonstrated sustained drug release over 20 days. Conclusions: POx represents a promising alternative to PEG for the formulation of CBD-loaded PLGA microspheres, offering enhanced physicochemical stability and biological compatibility. This platform supports the development of safe and effective long-acting injectable CBD therapies and consideration of POx as an alternative to PEG. Full article

Multi-material structures based on titanium alloys represent a promising approach for the fabrication of functionally graded orthopedic implants capable of combining high mechanical strength with reduced stiffness to minimize the stress-shielding effect. In the present work, multi-material Ti15Ta/Ti6Al4V specimens were fabricated by laser powder bed fusion (L-PBF) for the first time, and the processing parameters of the transition zone were systematically optimized. Three regimes were investigated: baseline (93 J/mm³), double scanning (186 J/mm³), and reduced speed (116 J/mm³). The microstructure and elemental distribution were examined by SEM and EDS; mechanical properties were evaluated through tensile testing and microhardness measurements; biocompatibility was assessed using osteoblasts and gingival fibroblasts. The double scanning regime provided the highest density of the transition zone (99.49%). Tensile failure of the specimens occurred in the Ti15Ta region, confirming the quality of the metallurgical bond. The ultimate tensile strength ranged from 534 to 543 MPa with an elongation at break of 15.7–16.4%. Heat treatment at 875 °C led to the formation of an equilibrium lamellar microstructure and smoothing of the interface. Cell viability on both alloys exceeded 88% as confirmed by flow cytometry and remained above the 70% non-cytotoxicity threshold defined by ISO 10993-5. The obtained results demonstrate the technological feasibility of fabricating multi-material Ti15Ta/Ti6Al4V structures and achieving high-quality metallurgical bonding, which constitutes a necessary first step toward the development of functionally graded orthopedic implants. Full article

Objective: Rare-earth elements are extensively employed across diverse industrial sectors, increasingly raising concerns about their potential health hazards in both occupational and environmental contexts. Samarium oxide (Sm₂O₃), a routinely processed rare-earth product, reproducibly precipitates pulmonary fibrosis in experimental models, yet the molecular circuitry that transduces its fibrogenic signal remains almost entirely unmapped. This study aims to elucidate the role of miR-214-3p in Sm₂O₃-induced pulmonary fibrosis and to investigate its regulatory mechanism at the molecular level. Methods: A murine model of pulmonary fibrosis was established via intratracheal instillation of Sm₂O₃, and histopathological changes were assessed using hematoxylin and eosin (H&E) and Masson’s trichrome staining. RNA sequencing was performed on lung tissues to identify differentially expressed mRNAs. Leveraging our previously generated miRNA landscape of Sm₂O₃-exposed lungs, we subjected the dataset to Gene Ontology and KEGG enrichment analyses, which convergently identified miR-214-3p as the top-ranking candidate regulator of the fibrogenic MAPK axis. The direct targeting of MAP2K3 by miR-214-3p was validated using a dual-luciferase reporter assay. Expression levels of fibrotic markers (α-SMA, Collagen I) and key components of the MAPK signaling pathway (MAP2K3, p-MAPK14, MST1) were quantified in both in vivo and in vitro models using qRT-PCR and Western blotting. Gain- and loss-of-function studies, complemented by rescue assays, were performed in human embryonic lung fibroblasts (HELFs) via transient transfection of miR-214-3p mimics, inhibitors, or MAP2K3-overexpression plasmids. Cell proliferation was evaluated using the EdU assay, and TGF-β1 secretion was measured by ELISA. Results: Sm₂O₃ exposure induced significant pulmonary fibrosis in mice, accompanied by marked downregulation of miR-214-3p and upregulation of MAP2K3 in lung tissues. Overexpression of miR-214-3p or silencing of MAP2K3 effectively suppressed Sm₂O₃-induced fibroblast activation, including reduced cell proliferation, decreased expression of α-SMA and Collagen I, and inhibition of p38 MAPK phosphorylation. Notably, ectopic overexpression of MAP2K3 reversed the protective effects conferred by miR-214-3p, confirming a functional rescue. Conclusions: miR-214-3p directly silences MAP2K3, thereby blunting p38 MAPK-driven fibrogenesis after Sm₂O₃ exposure. Our data unveil a miR-214-3p–MAP2K3–p38 MAPK axis that constitutes a readily druggable target for rare-earth-element-induced pulmonary fibrosis. Full article

Acute and chronic wounds are a major clinical burden, with persistent inflammation, impaired fibroblast function, defective angiogenesis, and disordered extracellular matrix deposition. The translational potential of existing in vitro models is limited by their poor durability and physiological relevance. The present paper aims to develop a robust in vitro organotypic model to simulate the early phases of both acute and chronic wounds and to validate it by testing the biocompatibility of clinically available wound dressings. Human fibroblasts and vascular endothelial cell lines were cultured at a ratio of 1:1 for 48 h, either on uncoated tissue culture plastic or on tissue culture plastic coated with a synthetic substrate (PhenoDrive-Y) that biomimics the extracellular matrix and promotes cell organization into tissue-like structures on a 2D plane (i.e., angiogenesis sprouting and fibroblast organization around it). Wound conditions were then created by damaging the formed structures using a conventional scratch procedure and introducing U937 human macrophage cells to the model to simulate either the onset of an acute wound or that of a chronic wound through the simultaneous spiking of the culture with relevant cytokines, i.e., IL-6 and TNF-α. The formation of new tissue-like structures in the scratch area was quantified by the extent of scratch closure after a further 24 h of incubation. Morphological analysis of wound healing was performed by light microscopy, while angiogenesis was assessed by CD31 immunostaining by confocal microscopy. The deposition of components of the extracellular matrix was determined both qualitatively and quantitatively by Picrosirius Red staining for collagen production and by Alcian Blue staining for glycosoaminoglycan synthesis on the adhering cells and their supernatants. Macrophage polarization into either M1 or M2 phenotype was studied by immunostaining with iNOS (M1) and CD206 (M2) antibodies by confocal microscopy. The model was validated by studying the gap closure areas in simulated acute and chronic wound-like conditions when incubated with clinically available wound dressings, N-A Ultra and Kaltostat. PhenoDrive-Y allowed the formation of tissue-like structures on the 2D tissue culture plane as opposed to the formation of cell monolayers on the uncoated tissue culture plastic. Upon mechanical damage, cell migration was significantly different; uncoated control co-cultures achieved complete closure as an indistinct monolayer by 24 h, while the organotypic wound models showed a slower percentage of damage closure. A further delay in the closure of the damaged area was observed when chronic wound-like conditions were simulated. Angiogenesis in chronic wound conditions was considerably impaired compared to the acute conditions. The analysis of the extracellular matrix component synthesis, specifically collagen and polysaccharides, revealed the deposition of dense, organized collagen fibers in the acute wound model, in contrast to the thin, fragmented collagen fibers and intracellular polysaccharides observed under chronic wound-like conditions. This corresponded to a statistically significant increase in the levels of both collagen and polysaccharides detected as soluble molecules in the supernatants. Macrophage polarization showed no statistically significant differences in the acute and chronic wound models, though iNOS did significantly decrease after N-A application in acute and chronic models. However, acute wound-like conditions showed a restoration of the vascularized tissue-like structures after treatment with these types of dressings, albeit through different organizational pathways, whereas only minimal improvement was noted under chronic wound conditions, particularly in the case of the N-A dressing. The organotypic dermis model for the onsets of acute and chronic wounds emerges as a highly versatile tool to understand healing mechanisms in the absence or presence of co-morbidities and to assess the biocompatibility of wound dressings as well as the safety, efficacy and dosage of drugs. Full article

The brewing process generates substantial by-products rich in potentially bioactive compounds (e.g., polyphenols and fermentation metabolites), providing a sustainable and appealing source of cosmetic ingredients. Oil-in-water (O/W) emulsions containing 20% (w/w) aqueous extracts from Bionda Triplo Malto beer, wort, and key brewing by-products (hops, yeast, and spent grain) were developed and evaluated using a combined in vitro–in vivo approach. Aqueous extracts were first screened on human immortalized dermal fibroblasts (BJ-5ta) at 0.25–1 mg/mL for cytocompatibility and antioxidant activity. Within this concentration range, no significant changes in cell viability or intracellular antioxidant capacity under UV stress were detected, suggesting cytocompatibility but limited inherent activity. When incorporated into O/W emulsions and tested at an active-equivalent concentration of 10 mg/mL, the formulations increased fibroblast metabolic activity and antioxidant response. In contrast, free extracts at 10 mg/mL showed concentration-dependent cytotoxicity for some matrices, with beer- and yeast-based emulsions demonstrating the strongest effects. The emulsions exhibited good physicochemical stability (pH ~5.7–6.2; viscosity 4750–5150 mPa·s), passed the ISO 11930:2012 challenge test, and were well tolerated in patch testing. In a double-blind, randomized split-forearm study on 50 healthy volunteers over 30 days, beer, yeast, and spent grain-based formulations improved skin parameters versus baseline. TEWL decreased (e.g., beer: 16.22 ± 5.12 to 10.77 ± 2.22 mg·m⁻²·h⁻¹; yeast: 16.29 ± 5.66 to 10.18 ± 1.08; spent grain: 14.45 ± 4.34 to 11.66 ± 2.28), hydration increased (beer: 35.15 ± 5.93 to 42.26 ± 3.78; yeast: 33.27 ± 4.87 to 42.92 ± 2.48; spent grain: 34.22 ± 5.19 to 41.16 ± 3.17, and elasticity improved for beer and yeast formulations (62.33 ± 3.27 to 70.24 ± 2.12 N/m) and yeast (61.21 ± 4.72 to 72.13 ± 5.55 N/m). Based on these findings, brewing-derived ingredients demonstrate potential as cosmetic actives, with formulation critically determining their clinical efficacy. Full article