BETAINE

Skin aging involves complex mechanisms such as overactivation of neuromuscular signals and oxidative stress. Herein, we developed a synergistic transdermal delivery system combining self-assembled tripeptide nanoparticles (DAC-SAPs) and a ternary deep eutectic solvent (DES, betaine-glycerol-propylene glycol, BGP) for anti-aging. DAC-SAP integrates dipeptide diaminobutyryl benzamide diacetate (DDB), argireline (ARG), and μ-conotoxin (CTX) into a single nanostructure through hydrophobic interactions, hydrogen bonds, and electrostatically driven molecular self-assembly. This spatial co-localization ensures synchronous delivery and spatiotemporal synergy, effectively inhibiting neuromuscular signaling. BGP DES optimizes polarity regulation, destroys stratum corneum lipids, and significantly promotes transdermal penetration. Molecular dynamics (MD) simulations reveal a dual permeation-promoting mechanism, with an appropriate nanostructure size reducing transmembrane resistance, whereas DES promotes lipid mobility and weakens tight junctions in the stratum corneum (SC). In vitro, in vivo, and exploratory clinical assessments demonstrate that DAC-SAP/BGP significantly inhibits sodium and calcium channel activity, reduces acetylcholine (ACh) secretion, and improves skin elasticity and wrinkle parameters. This multicomponent system achieves a synergistic anti-aging effect by blocking and enhancing the transmission of neuromuscular signals, thus providing a new strategy for anti-aging skin care.

Bacterial infections represent a major bottleneck to wound repair and a critical clinical challenge. To address these dilemma, a hydrogel dressing based on furoic acid and betaine co-modified chitosan (FUA-CS-BE) was developed in this study. The in vivo therapeutic efficacy of FUA-CS-BE hydrogel (FUA-CS-BE gel ) on Staphylococcus aureus (S. aureus)-infected full-thickness skin wounds was evaluated. Studies found that the FUA-CS-BE gel treatment led to a reduction in bacterial burden at the wound site, accelerating wound healing. Meanwhile, FUA-CS-BE gel modulated the inflammatory microenvironment by down-regulating the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thereby mitigating excessive inflammatory responses. Furthermore, FUA-CS-BE gel significantly promoted micro-vascular angiogenesis, as indicated by up-regulated expression of key angiogenic markers, including vascular endothelial growth factor (VEGF) and CD31. These synergistic effects collectively accelerated wound healing and ultimately enhance the repair efficiency of S. aureus-infected wounds. FUA‑CS‑BE gel exerted antibacterial activity via a dual mechanism: disrupting bacterial membrane integrity and interfering with metabolic pathways. Taken together, these results demonstrate that FUA-CS-BE gel holds great promise as a candidate for the clinical management of bacterial-infected wounds.

Hair loss is a widespread condition with androgenetic alopecia (AGA) representing the most prevalent subtype. The excessive accumulation of reactive oxygen species (ROS) in the perifollicular microenvironment and subsequent dysregulation of the follicular milieu is recognized as a major driver underlying the pathogenesis of AGA. Hydroxytyrosol (HT), a natural polyphenolic compound with potent antioxidant activity, has demonstrated protective effects against oxidative stress-induced inflammation in dermal cells. However, the clinical application of HT is limited by its high hydrophilicity, which restricts penetration across the skin lipid barrier and results in poor cutaneous absorption. Additionally, HT is prone to oxidation, further compromising its efficacy. To overcome these challenges, we developed a pro-permeable deep eutectic solvent (DES)-based system, composed of betaine, urea, and lactic (BUL), to facilitate the transdermal delivery of HT while preserving bioactivity. The BUL-based delivery system enabled cutaneous penetration to a depth of at least 180 µm, achieving over threefold greater permeation than aqueous solutions. In vivo studies confirmed that HT@BUL effectively promoted hair regrowth and exhibited high biocompatibility, whereas results of in vitro assays demonstrated that HT-loaded BUL exhibited intrinsic ROS-scavenging activity, ability to stimulate proliferation, and capacity to mitigate cellular senescence. Our research highlights the therapeutic potential of combining antioxidant molecules with BUL for the promotion of hair regrowth.

Recent progress in supramolecule research has led to a surge in its application in cosmetic products. However, comprehensive investigation of the potential benefits, especially differentiating biological activities and associating that with physical-chemical properties, remains to be established. The current study aimed to investigate the supramolecular salicylic acid-betaine (Supra-SA-B) compared to its physical mixture (SA+B) for effects on epidermal homeostasis and topical insult potential. The structure of supra-SA-B and SA+B was characterized by a powder X-ray diffractometer. Skin tolerance was evaluated by applying SA, Supra-SA-B, and SA+B to human keratinocytes or SkinEthic™ reconstructed human epidermis (RHE) models. Inflammatory cytokines were assessed by Luminex assay. Histological morphology was evaluated by hematoxylin-eosin staining, with aquaporin-3 (AQP3) and Ki67 measured by immunofluorescence. RNA sequencing characterized overall biological response. Characteristic peaks remained the same for Supra-SA-B after freeze-drying verified that their crystalline structures were retained in the current solution. Supra-SA-B treated groups demonstrated significantly higher viabilities compared to SA or SA+B. With 18-h of treatment, Supra-SA-B treated group released fewer cytokines. In addition, Supra-SA-B demonstrated a better hydration effect with increased AQP3 expression and more organized epidermal structure. Consistent result was observed in the RNA transcriptomic profiles of RHE models. Supra-SA-B did not induce major transcriptome drift as compared to SA or SA+B, with less evident negative impact on loricrin, and late cornified envelope gene expression. Hyaluronic acid synthase boosting was maintained. Supra-SA-B ameliorated skin tolerance risk for SA, enhanced hydration with less insult on barrier functions, suggesting promising potential for cosmetic application.

Betaines are natural nitrogen-containing compounds widely distributed in plant-derived foods and animal tissues, where they function primarily as osmolytes, chaperons, and methyl donors. As such, they have attracted increasing interest as dietary components and metabolic biomarkers in human nutrition. This study provides a comparative characterization of glycine betaine (GlyBet) and proline betaine (ProBet) by combining targeted LC-MS quantification in a representative selection of plant-based foods with complementary in silico analyses and integration of dietary intake estimates derived from published nutritional and metabolomic studies, together with human metabolomic data. A validated HPLC-ESI-MS method was applied to quantify GlyBet and ProBet across cereals, pseudocereals, vegetables, and fruits. GlyBet was found to be predominantly abundant in leafy vegetables and in several cereal and pseudocereal flours, whereas ProBet was highly enriched in citrus fruits, particularly bergamot, chinotto, and bitter orange. In silico ADMET predictions were used to provide a qualitative and comparative description of the pharmacokinetic and safety-related properties of the two betaines, indicating broadly similar hydrophilic profiles with modest differences in solubility, clearance, and predicted skin sensitization. Similarity-based target prediction analyses, used in an exploratory framework, suggest distinct contextual tendencies for the two betaines. GlyBet is primarily associated with pathways related to one-carbon metabolism and cellular stress responses, whereas ProBet shows a closer contextual association with signaling-related processes. By integrating experimental data, computational analyses, and human metabolomic information, this work supports the interpretation of betaines as biomarkers of dietary intake and systemic metabolic status.

Soil salinity is a major constraint to crop establishment and yield, particularly during germination and early seedling development of Brassica napus. Here, we report that zinc oxide nanoparticles (ZnONPs) biosynthesized using Pseudomonas aeruginosa alleviate salinity stress through coordinated physiological, biochemical, and molecular mechanisms. Comprehensive physicochemical analyses confirmed the formation of hexagonal wurtzite ZnONPs with a plate-like morphology (thickness ~ 54.5 nm) and an optical band gap of 3.01 eV. Canola seeds were primed with ZnONPs (25-100 mg L⁻¹) under control or 150 mM NaCl stress and subsequently grown in hydroponics. Salt stress reduced germination (41%), biomass, and vigor, while elevating lipid peroxidation and reactive oxygen species. ZnONPs, particularly at 50 mg L⁻¹, restored germination to control levels, enhanced shoot (52 cm) and root (35 cm) elongation, and nearly doubled salt-stressed biomass. ZnONP treatment suppressed malondialdehyde and H₂O₂ accumulation below control values, while up-regulating superoxide dismutase and catalase activity. Furthermore, ZnONPs reduced osmolyte (proline and glycine betaine) accumulation, increased chlorophyll content, lowered Na⁺, and elevated K⁺ and Zn uptake, thereby improving ion homeostasis. Transcript analysis revealed that salinity strongly induced the stress-responsive kinase BnSRK2D (~ 86-fold) and repressed auxin-responsive genes, whereas 50 mg L⁻¹ ZnONPs normalized these responses, down-modulating stress signaling and restoring auxin pathways. Collectively, these findings demonstrate that biogenic ZnONPs mitigate salinity stress in B. napus through integrated regulation of antioxidant defense, ion balance, and hormone-mediated gene expression, highlighting their potential as sustainable nanopriming agents for crop improvement under saline conditions.

Traditional sensors, in long-term skin contact, prone to microbial growth, risking skin allergies and infections. To address this issue, a novel deep eutectic gel composite-polyacrylamide-gelatin-Dalbergia benthamii Prain total flavonoids (PAMG-DbTF)-was developed by integrating betaine-urea-based natural deep eutectic solvent (NADES) with polyacrylamide (PAM) and gelatin-a biopolymer derived from collagen-via physicochemical crosslinking. As the core biopolymer, gelatin played a pivotal role in constructing the stable interpenetrating network: its intrinsic amino acid residues formed hydrogen bonds with PAM chains and NADES, which was confirmed by FT-IR, SEM, XRD, XPS and TGA analyses. This gelatin-driven network endowed the gel with excellent mechanical and stability properties, including a tensile strain of 330%, a swelling ratio of 220%, 90% water retention at 48 h, and antifreezing performance at -20°C. The DbTF-loaded gel showed synergistic antibacterial activity (100% against E. coli) and antioxidant capacity (70% DPPH scavenging rate). As a flexible strain sensor, PAMG-2 demonstrated stable relative resistance changes (ΔR/R 0 ) under cyclic loading (500 cycles at 40% strain) and real-time monitoring of human motions (throat vocalization, joint bending), where gelatin's elasticity ensures signal repeatability. This gelatin-centered multifunctional deep eutectic gel highlights the critical role of biopolymers in advanced wearable biomedical devices and environmental monitoring.

Shifts in the skin microbiome have shown a close link to chronological age. However, the contribution of the skin microbiome in skin-aging phenotypes remains unclear. To explore this, we performed phenotypic, metabolomic, metagenomic, and functional analyses on a cohort with divergent skin-aging phenotypes. Genome-scale metabolic models (GEMs) integrated with metabolomic analysis revealed that Stenotrophomonas maltophilia, enriched in the younger group (categorized by AI-predicted age and skin elasticity), utilizes the glutathione cycle to maintain redox homeostasis. Cellular experiments showed its metabolites enhanced GSH synthesis and alleviated oxidative-stress-induced phenotypic skin-aging by upregulating key genes in fibroblasts, including GCLM, PGD, SOD2, and NQO1. In addition, GEMs highlighted its potential in maintaining youthful skin phenotypes through the regulation of host metabolic pathways involving betaine, lysolecithin, and porphyrin. In parallel, Acinetobacter guillouiae was found to influence host melanin metabolism by degrading dopamine (DA) and 3-methoxytyramine (3-MT), offering potential therapeutic strategies for mitigating pigmentation. Our findings highlight the dynamic interplay between skin microbiota and the host in phenotypic skin-aging, offering new insights for designing interventions to maintain youthful skin. Video Abstract.

Despite regulatory bans on hazardous substances such as hydroquinone, glucocorticoids, and retinoids, these compounds are still detected in cosmetic products, underscoring the need for reliable analytical methods. This study evaluated four sample preparation approaches for detecting banned ingredients: ultrasound-assisted extraction (UAE), "Quick, Easy, Cheap, Effective, Rugged, Safe" (QuEChERS), solid-phase extraction (SPE), and natural deep eutectic solvents (NaDESs). High-performance liquid chromatography with diode array detection (HPLC-DAD) revealed low recoveries for QuEChERS and SPE. In contrast, NaDESs prepared with choline chloride (ChCl) or betaine as hydrogen bond acceptors (HBAs) and 1,3-propanediol as a hydrogen bond donor (HBD) achieved significantly higher recoveries. In particular the ChCl-1,3-propanediol NaDES (1:4 M ratio) provided recoveries of 83.96-105.45%. UAE using methanol yielded comparable recoveries (91.29-106.81%), but the NaDES approach was more environmentally sustainable due to reduced organic solvent use. Method validation following International Conference on Harmonization (ICH) guidelines confirmed acceptable sensitivity (limit of detection: 0.27-1.59 μg/mL; limit of quantification: 0.81-4.81 μg/mL), recovery, linearity, precision, and accuracy. Target analytes were further verified using liquid chromatography-tandem mass spectrometry. These results demonstrate the feasibility of applying green solvents in cosmetic analysis and highlight a sustainable, effective method for detecting banned skin-whitening agents.

Preservatives are primarily used for their antimicrobial properties and form an important component of food, cosmetic, and drug formulations. The efficacy of preservatives depends on various factors, which include the bacterial membrane composition and the interaction between components of a specific formulation. Molecules such as phenoxyethanol (POE), caprylylglycol (CPG), and methylparaben (MEP) are widely used as preservatives in the food and cosmetic industries; however, a molecular understanding of their interactions with surfactants and the kinetics of membrane partitioning remains unexplored. In this study, coarse-grained molecular dynamics simulations were carried out to evaluate and quantify the kinetics of membrane partitioning for preservatives and surfactants in the Escherichia coli inner phospholipid membrane. We propose a mass-transfer-based model to determine membrane partitioning kinetics. Faster kinetics were observed for first-order partitioning of POE and MEP (τ ∼ 0.01 μs) when compared with zeroth-order kinetics (τ ∼ 0.1 μs) for CPG. In contrast, surfactants such as sodium laureth sulfate (SLES) and cocamidopropyl betaine (CAPB) follow zeroth-order membrane partitioning kinetics with significantly higher time constants (1.5-10 μs). Interestingly, zeroth-order kinetics occurred when micellar aggregates were present, and the rate-controlling step was the slow rate of release of single molecules from the aggregate, in comparison to faster membrane uptake kinetics. Using a sequential micellar breakup model with single surfactant release dynamics, we analytically recover this unique zeroth-order membrane partitioning kinetics. In preservative-surfactant mixtures, the kinetics of preservative partitioning were found to decrease by a factor of 2-10. Significantly, the equilibrium membrane saturation coefficients for both preservatives and surfactant remained invariant in the mixtures due to the wide separation of partitioning time scales for the surfactants and preservatives. The kinetic models developed in this study can be used to quantify membrane partitioning of preservatives and understand the influence of surfactants in specific formulations.

Environmental stressors, including climate change, pollution, and lifestyle factors, can disrupt the skin barrier, leading to dryness and exacerbating conditions such as atopic dermatitis (AD), acne, and psoriasis. Effective barrier repair requires maintaining hydration and lipid balance, particularly the ceramide-cholesterol-fatty acid ratio of 3:1:1, which is recommended by dermatological societies for optimal skin restoration. Although traditional moisturizers provide hydration through occlusives, humectants, and emollients, they often do not achieve sustained barrier repair or adequate intracellular hydration. Next-generation moisturizers are designed with bioactive ingredients that aim to both hydrate and support barrier repair by reducing inflammation, modulating the microbiome, and promoting skin homeostasis. Oryza Ceramax (Alaina Healthcare; Alembic Pharmaceuticals Pvt. Ltd., Vadodara, India), a next-generation moisturizer incorporating a 3:1:1 ceramide-cholesterol-fatty acid ratio, includes aquaporin (AQP) boosters, naturally sourced betaine, saffron extract, hyaluronic acid, and other bioactive components that resemble the skin's natural lipid composition. Clinical evidence supports the efficacy of ceramide-dominant formulations in improving hydration and reducing transepidermal water loss (TEWL), with studies reporting TEWL reductions of approximately 10% and hydration improvement lasting up to 72 hours. Oryza Ceramax is formulated to align with dermatologic recommendations for use in dry or impaired skin and is free from parabens, alcohol, mineral oil, and soap (PAMS-free). Its formulation characteristics are consistent with evidence-based principles for skin barrier protection and hydration maintenance. This narrative review examines the science underlying multi-pathway approaches to skin barrier repair and hydration, using Oryza Ceramax as an example of a ceramide- and AQP-based formulation. The findings highlight emerging strategies in moisturizer design but also emphasize the need for independent, well-controlled clinical studies to validate these observations.

Abstracts: Background: Hair dye-related allergic contact dermatitis (ACD) is a common problem among both consumers and professionals. The main sensitizers are aromatic amines such as para-phenylenediamine (PPD) and toluene-2,5-diamine (TDA), which can also cross-react with chemically related compounds. Objective: To analyze patch-test results from patients with suspected hair dye-related ACD, focusing on the prevalence of sensitization to hair dye allergens, cross-reactivity patterns, and occupational differences. Methods: We retrospectively reviewed 666 patients patch-tested between 2005 and 2023 at the Patch Test Clinic of Andreas Sygros Hospital, Athens, Greece. All patients were tested with the European baseline and extended hairdresser series. Results were evaluated according to the International Contact Dermatitis Research Group and European Society of Contact Dermatitis criteria. Logistic regression was used to calculate odds ratios for co-sensitization, adjusted for sex and age. Results: Overall, 82.4% of patients reacted to at least 1 allergen, with a median of 3 positive reactions. PPD was the most frequent allergen (47.9%), followed by TDA (35.9%) and nickel (41.1%). Significant co-sensitization was observed between PPD and several chemically related compounds, including 4-aminophenol, 3-aminophenol, benzocaine, textile dyes, hydroquinone, and pyrogallol ( P < 0.001). Similar associations were observed for TDA. Hairdressers were younger (mean 32.2 vs 40.7 years, P < 0.001) and had predominantly hand dermatitis (62.9%). Patients reacting to multiple hair dye components were significantly more likely to be sensitized to PPD. Co-sensitization between PPD and cocamidopropyl betaine likely reflected cosmetic co-exposure rather than structural cross-reactivity. Conclusions: PPD and TDA remain the dominant sensitizers in hair dye-related ACD, with strong cross-reactivity to aminophenols, benzocaine, and textile dyes. Extended patch testing is essential for accurate diagnosis, as 7% of para-amino-compound-sensitized patients would be missed by PPD testing alone. Occupational exposure and multi-allergen sensitization highlight the need for safer formulations and preventive strategies in hair dye use.