Translational application of human keratinocyte-fibroblast cell sheets for accelerated wound healing in a clinically relevant type 2 diabetic rat model.

BACKGROUND AIMS: Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like structure and secrete essential cytokines and growth factors that regulate the wound healing process. METHODS: This study aimed to evaluate the safety and therapeutic potential of human skin cell sheets to treat full-thickness skin defects in a rat model of type 2 diabetes. RESULTS: Our findings demonstrate that diabetic wounds transplanted with bilayered cell sheets resulted in accelerated re-epithelialization, increased angiogenesis, enhanced macrophage polarization and regeneration of tissue that closely resembled healthy skin. In contrast, the control group that did not receive cell sheet transplantation presented characteristic symptoms of impaired and delayed wound healing associated with type 2 diabetes. CONCLUSIONS: The secretory cytokines and the upregulation of Nrf2 expression in response to cell sheet transplantation are believed to have played a key role in the improved wound healing observed in diabetic rats. Our study suggests that human keratinocyte-fibroblast cell sheets hold great potential as a therapeutic alternative for diabetic ulcers.

Differential effects of benzo[a]pyrene exposure on glutathione and purine metabolism in keratinocytes: Dose-dependent and UV co-exposure effects.

Polycyclic aromatic hydrocarbons with the key substance benzo[a]pyrene (B[a]P) are widespread pollutants in the environment and at working places. Nonetheless, the exact underlying mechanisms of toxicological effects caused by B[a]P especially in absence and presence of UV irradiation remain uncertain. This study examines variations in exposure conditions: low B[a]P (4 nM), low B[a]P + UV and high B[a]P (4 µM), selected based on pertinent cytotoxicity assessments. Following cell viability evaluations post-treatment with varied B[a]P concentrations and UV irradiation, the identified concentrations underwent detailed metabolomic analysis via gas chromatography-mass spectrometry. Subsequently, resulting changes in metabolic profiles across these distinct exposure groups are comprehensively compared. Chemometric analyses showed modest regulation of metabolites after low B[a]P exposure compared to control conditions. High B[a]P and low B[a]P + UV exposure significantly increased regulation of metabolic pathways, indicating that additional UV irradiation plus low B[a]P is as demanding for the cells as higher B[a]P treatment alone. Further analysis revealed exposure-dependent regulation of glutathione-important for oxidative defence-and purine metabolism-important for DNA base synthesis. Only after low B[a]P, oxidative defence appeared to be able to compensate for B[a]P-induced perturbations of the oxidative homeostasis. In contrast, purine metabolism already responded towards adversity at low B[a]P. The metabolomic results give an insight into the mechanisms leading to the toxic response and confirm the strong effects of co-exposure on oxidative defence and DNA repair in the model studied.

Designed Mannosylerythritol Lipid Analogues Exhibiting Both Selective Cytotoxicity Against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells.

Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-ß-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.

The influence of Leucidal, a natural cosmetic preservative, on fibroblast and keratinocytes. Studies on cells and on model membrane systems.

The aim of this work was to investigate the influence of Leucidal® Liquid (abbr. Leucidal), which is recommended as a natural cosmetic ingredient of antimicrobial properties, on model membranes of keratinocytes and fibroblasts. The toxicity tests on cell lines were also performed to allow for a more detailed discussion of the results. As model membrane systems the lipid Langmuir monolayers were applied. During the investigations, the surface pressure/area measurements, penetration studies and Brewster Angle Microscopy (BAM) visualization were performed for one component and mixed lipid monolayers. It was evidenced that at the membrane - corresponding conditions, the components of Leucidal do not penetrate either model keratinocyte and fibroblast membranes or one component films composed of the major lipids of skin cell membranes. Leucidal makes these systems slightly more expanded and less stable, however this is not reflected in the changes in the film morphology. Only the ceramide systems were sensitive to the presence of Leucidal, i.e. the incorporation of Leucidal components manifested well in the decrease of the films' condensation and alterations in their morphology. The tests on cells demonstrated that Leucidal is non toxic for these types of cells at the concentrations suggested by the producer. A thorough comparison of these results with those published for bacteria model membranes enabled us to discuss them in the context of the mechanism of action of Leucidal components. It was concluded that Leucidal components are of low affinity to the skin cellular model membranes of low content of Leucidal-sensitive ceramides and are not toxic for fibroblast and keratinocyte cell lines. Moreover, the lipid composition of the membrane and its molecular organization can be important targets for Leucidal components, decisive from the point of view of the activity and selectivity of the studied composition.

Stem-Cell-Regenerative and Protective Effects of Squid (Symplectoteuthis oualaniensis) Skin Collagen Peptides against H2O2-Induced Fibroblast Injury.

Recently, there has been a growing interest in collagen peptides derived from marine sources for their notable ability to protect skin cells against apoptosis induced by oxidants. Therefore, the current study aimed to investigate the fundamental properties of collagen peptides, including their physicochemical, thermal, structural, stem-cell-regenerative, and skin-cell-protective effects, in comparison to commercial collagen peptides. The acid-soluble (ASC) and pepsin-soluble (PSC) collagens exhibited three distinct bands on SDS-PAGE, namely α (α1 and α2), ß, and γ chains, confirming a type I pattern. The thermal profiles obtained from TG and DSC analyses confirmed the denaturation of PSC and ASC at temperatures ranging from 51.94 to 56.4 °C and from 52.07 to 56.53 °C, respectively. The purified collagen peptides were analyzed using SDS-PAGE and MALDI-TOF mass spectrometry, revealing a mass range of 900-15,000 Da. Furthermore, the de novo peptide sequence analysis confirmed the presence of the Gly-X-Y repeating sequence in collagen peptides. Collagen peptide treatments significantly enhanced HFF-1 cell proliferation and migration compared to the control group. ELISA results confirmed the potential interactions between collagen peptides and HFF-1 cells through α2ß1, α10ß1, and α11ß1 integrin receptors. Notably, collagen peptide treatment effectively restored the proliferation of HFF-1 cells damaged by H2O2. Consequently, the advantageous characteristics of squid skin collagen peptides highlight their promising role in regenerative medicine.

Copper/Tin Nanocomposites-Loaded Exosomes Induce Apoptosis and Cell Cycle Arrest at G0/G1 Phase in Skin Cancer Cell Line.

This study aims to explore the efficacy of Copper/Tin (CuS/SnS) nanocomposites loaded into exosomes against skin cancer A431 cell line. CuS/SnS nanocomposites (S1, S2, S3) were synthesized and characterized, then loaded into exosomes (Exo) (S1-Exo, S2-Exo and S3-Exo) and characterized. After that, the loaded samples were investigated in vitro against A431 using cytotoxicity, apoptosis, and cell cycle assays. CuS/SnS nanocomposites were indexed to hexagonal CuS structure and orthorhombic α-SnS phase and showed nano-rode shape. The exosomes loaded with nanocomposites were regular and rounded within the size of 120 nm, with no signs of broken exosomes or leakage of their contents. The cytotoxicity assay indicated the enhanced cytotoxic of S1-Exo versus the free nano-form S1 on A431. Interestingly, S1-Exo recorded 1.109 times more than DOX in its anti-skin cancer capacity. Moreover, S1-Exo recorded 40.2% for early apoptosis and 22.1% for late apoptosis. Furthermore, it displayed impact in arresting the cancer cell cycle at G0/G1 phase and reducing G2/M phase. Noteworthy, loaded nanocomposites were safe against normal HSF skin cells. In conclusion, the loaded CuS/SnS nanocomposites into the exosomes could be of great potential as anti-skin cancer candidates through induction of apoptosis and promotion of the cell cycle arrest at G0/G1 phase.

Comparison of the Antioxidant and Cytoprotective Properties of Extracts from Different Cultivars of Cornus mas L.

Cornus mas L. is a rich source of vitamin C and polyphenols. Due to their health-benefit properties, C. mas L. extracts have been used in, e.g., dermatology and cosmetology, and as a food supplement. Peroxisome proliferator-activated receptor gamma (PPARγ) and its co-activator (PGC-1α) are now suspected to be the main target of active substances from C. mass extracts, especially polyphenols. Moreover, the PPARγ pathway is involved in the development of different diseases, such as type 2 diabetes mellitus (DM2), cancers, skin irritation, and inflammation. Therefore, the aim of the present study was to evaluate the PPARγ pathway activation by the most popular water and ethanol extracts from specific C. mas L. cultivars in an in vitro model of the human normal fibroblast (BJ) cell line. We analyzed the content of biologically active compounds in the extracts using the UPLC-DAD-MS technique and revealed the presence of many polyphenols, including gallic, quinic, protocatechuic, chlorogenic, and ellagic acids as well as iridoids, with loganic acid being the predominant component. In addition, the extracts contained cyanidin 3-O-galactoside, pelargonidin 3-O-glucoside, and quercetin 3-glucuronide. The water-ethanol dark red extract (DRE) showed the strongest antioxidant activity. Cytotoxicity was assessed in a normal skin cell line, and positive effects of all the extracts with concentrations ranging from 10 to 1000 µg/mL on the cells were shown. Our data show that the studied extracts activate the PPARγ/PGC-1α molecular pathway in BJ cells and, through this mechanism, initiate antioxidant response. Moreover, the activation of this molecular pathway may increase insulin sensitivity in DM2 and reduce skin irritation.

New Polymeric Hydrogels with Cannabidiol and α-Terpineol as Potential Materials for Skin Regeneration-Synthesis and Physicochemical and Biological Characterization.

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.

ROS Scavenging Effect of Selected Isoflavones in Provoked Oxidative Stress Conditions in Human Skin Fibroblasts and Keratinocytes.

Isoflavones, belonging to polyphenolic compounds, show structural similarity to natural estrogens, and in this context, they have been extensively studied. Some of them are also applied as cosmetic additives; however, little is known regarding their effects on skin cells. In this investigation, common isoflavones, including genistein, daidzein, glycitein, formononetin, and biochanin A, as well as coumestrol, were evaluated for antioxidant activity and their impact on human skin fibroblasts and keratinocytes. Antioxidant effects were assessed using DPPH, ABTS, and FRAP tests, and the ability to scavenge reactive oxygen species (ROS) was tested in cells with H2O2-provoked oxidative stress. The impact on the activity of antioxidant enzymes (SOD, CAT, GSH) and lipid peroxidation (MDA) was also explored. As shown by Alamar Blue and neutral red uptake assays, the compounds were not toxic within the tested concentration range, and formononetin and coumestrol even demonstrated a stimulatory effect on cells. Coumestrol and biochanin A demonstrated significant antioxidative potential, leading to a significant decrease in ROS in the cells stimulated by H2O2. Furthermore, they influenced enzyme activity, preventing depletion during induced oxidative stress, and also reduced MDA levels, demonstrating protection against lipid peroxidation. In turn, genistein, daidzein, and glycitein exhibited low antioxidant capacity.

Anti-skin ageing activities of rice (Oryza sativa) bran soft and hard waxes in cultured skin cells.

OBJECTIVE: Rice (Oryza sativa) bran waxes, the by-products of rice bran oil manufacturing, are widely used as inactive components in several preparations. Nevertheless, the function of rice bran waxes against skin ageing has never been reported. This study aimed to investigate thermal property and fatty acid profile of rice bran waxes, including rice bran soft (RBS) and hard (RBH) waxes, and the activities against skin ageing in cultured skin cells. METHODS: Thermal property and fatty acid profile of rice bran waxes were analysed by differential scanning calorimetry and gas chromatography-mass spectrometry, respectively. The cytotoxicity assay of waxes was performed in B16F10 melanoma cells, human skin fibroblasts and co-culture cells of HaCaT cells and human skin fibroblasts. The non-cytotoxic concentrations of waxes were evaluated for their activities against skin ageing, including melanogenesis assay, antioxidant activity, collagen content analysis, matrix metalloproteinase-1 and matrix metalloproteinase-2 inhibitory assay and anti-inflammatory activity. RESULTS: Thermal property indicated the endotherm peaks with melting temperatures at 40.89 ± 0.27°C and 69.64 ± 0.34°C for RBS and RBH, respectively. The main fatty acids in RBS were oleic (31.68 ± 0.75%) and linoleic acids (27.19 ± 0.40%), whereas those in RBH were palmitic (36.24 ± 1.08%) and stearic acids (35.21 ± 4.51%). The cytotoxicity assay in single cells and co-culture cells showed the non-cytotoxicity of RBS (0.0001-1 mg/mL) and RBH (0.0001-0.1 mg/mL). The anti-skin ageing activities of 1 mg/mL RBS and 0.1 mg/mL RBH included the melanogenesis inhibition by suppression of tyrosinase and tyrosinase-related protein-2 enzymes, the antioxidant activity by cellular protection against cell damage and cell death, the collagen stimulation, the matrix metalloproteinase-1 and matrix metalloproteinase-2 suppression and the anti-inflammation. CONCLUSIONS: The study results suggest that RBS and RBH can potentially be applied as the functional ingredients in formulations against skin ageing as well as provide the superior benefit on skin moisturization.

OBJECTIF: Les cires de son de riz (Oryza sativa) et les sous­produits de la fabrication de l'huile de son de riz sont largement utilisées comme composants inactifs dans plusieurs préparations. Néanmoins, l'effet des cires de son de riz contre le vieillissement de la peau n'a jamais été rapporté. Cette étude visait à étudier les propriétés thermiques et le profil d'acides gras des cires de son de riz, y compris les cires dures et douces de son de riz, et les activités contre le vieillissement de la peau dans les cellules cutanées en culture. MÉTHODES: La propriété thermique et le profil d'acides gras des cires de son de riz ont été analysés par calorimétrie différentielle à balayage et chromatographie en phase gazeuse couplée spectrométrie de masse, respectivement. Le dosage de la cytotoxicité des cires a été réalisé sur des cellules de mélanome B16F10, des fibroblastes de peau humaine, et des cellules de co­culture de cellules HaCaT et des fibroblastes de peau humaine. Les concentrations non cytotoxiques des cires ont été évaluées pour leurs activités contre le vieillissement de la peau, y compris l'analyse de la mélanogenèse, l'activité antioxydante, l'analyse de la teneur en collagène, le test de l'inhibiteur de la métalloprotéinase matricielle­1 et de la métalloprotéinase matricielle­2 et l'activité anti­inflammatoire. RÉSULTATS: La propriété thermique indiquait des pics endothermes avec des températures de fusion à 40,89 ± 0,27 °C et 69,64 ± 0,34 °C pour les cires dures et douces de son de riz, respectivement. Les principaux acides gras des cires douces de son de riz étaient des acides oléiques (31,68 ± 0,75 %) et des acides linoléiques (27,19 ± 0,40 %), tandis que ceux des cires dures de son de riz étaient des acides palmitiques (36,24 ± 1,08 %) et des acides stéariques (35,21 ± 4,51 %). Le dosage de la cytotoxicité dans les cellules individuelles et les cellules de co­culture a montré la non­cytotoxicité des cires douces de son de riz (0,0001 à 1 mg/ml) et des cires dures de son de riz (0,0001 à 0,1 mg/ml). Les activités antivieillissement de la peau de 1 mg/ml de cire douce de son de riz et de 0,1 mg/ml de cire dure de son de riz comprenaient l'inhibition de la mélanogenèse par suppression des enzymes de la tyrosinase et de la protéine liée à la tyrosinase 2, l'activité antioxydante par protection cellulaire contre les dommages et la mort cellulaires, la stimulation du collagène, la suppression de la métalloprotéinase matricielle­1 et la métalloprotéinase matricielle­2 et l'activité anti­inflammatoire. CONCLUSIONS: Les résultats de l'étude indiquent que les cires dures et douces de son de riz peuvent potentiellement être appliquées comme ingrédients fonctionnels dans des formulations contre le vieillissement de la peau et fournir un bénéfice supérieur en termes d'hydratation de la peau.

Ectoine Globally Hypomethylates DNA in Skin Cells and Suppresses Cancer Proliferation.

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the expression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of the well-known DNA protectant (ectoine) in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA epigenetic modifications-related gene analysis were performed. The results showed that extended ectoine treatment globally hypomethylated DNA in skin cells, especially in the CpG island (CGIs) element, and 5mC percentage was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation and did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3l, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Snrpn, and Mest. Overall, ectoine mildly demethylates DNA in skin cells, modulates the expression of epigenetic modification-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

Deep palm burn treated with enzymatic debridement followed by autologous skin cell suspension: a case study.

Despite improvements in treatment methods and outcomes, burns remain one of the principal causes of mortality and morbidity worldwide. Burns involving the hands are estimated to occur in >80% of people with burns. Hand burns have also been associated with long-term social, psychological and physical consequences that can impede a patient's full reintegration to the community and decrease their overall quality of life. Clinically, when the trajectory towards complete re-epithelialisation stalls in deep burn wounds of the hand, skin grafting is indicated, but cosmetic problems often remain. A recent publication highlighted common complications for burns involving the hand such as scar disturbances (26%) and scar contractures (14%). Innovative approaches with the potential to reduce the occurrence of complicating scar disturbances and contractures are sought by healthcare providers specialising in burns. This case report describes a novel approach to wound closure using a topical concentrate of proteolytic enzymes followed by the application of an autologous skin cell suspension. This combination was effective in achieving early and complete re-epithelialisation of a deep burn of the palm of a 28-year-old male patient, while potentially affording a favourable impact on hypertrophic scarring or scar contracture.

Comparative Analysis of Water Extracts from Roselle (Hibiscus sabdariffa L.) Plants and Callus Cells: Constituents, Effects on Human Skin Cells, and Transcriptome Profiles.

Roselle (Hibiscus sabdariffa L.) is a plant that has traditionally been used in various food and beverage products. Here, we investigated the potential of water extracts derived from Roselle leaves and callus cells for cosmetic and pharmaceutical purposes. We generated calluses from Roselle leaves and produced two different water extracts through heat extraction, which we named Hibiscus sabdariffa plant extract (HSPE) and Hibiscus sabdariffa callus extract (HSCE). HPLC analysis showed that the two extracts have different components, with nucleic acids and metabolites such as phenylalanine and tryptophan being the most common components in both extracts. In vitro assays demonstrated that HSCE has strong anti-melanogenic effects and functions for skin barrier and antioxidant activity. Transcriptome profiling of human skin cells treated with HSPE and HSCE showed significant differences, with HSPE having more effects on human skin cells. Up-regulated genes by HSPE function in angiogenesis, the oxidation-reduction process, and glycolysis, while up-regulated genes by HSCE encode ribosome proteins and IFI6, functioning in the healing of radiation-injured skin cells. Therefore, we suggest that the two extracts from Roselle should be applied differently for cosmetics and pharmaceutical purposes. Our findings demonstrate the potential of Roselle extracts as a natural source for skincare products.

Anti-Inflammatory and Protective Effects of Water Extract and Bioferment from Sambucus nigra Fruit in LPS-Induced Human Skin Fibroblasts.

In this study, an attempt was made to evaluate the antioxidant, anti-inflammatory and protective effects of the Sambucus nigra fruit extract and its ferment obtained by fermentation with kombucha tea fungus. For this purpose, fermented and non-fermented extracts were compared in terms of their chemical composition by the HPLC/ESI-MS chromatographic method. The antioxidant activity of the tested samples was assessed using DPPH and ABTS assays. Cytotoxicity was also determined using Alamar Blue and Neutral Red tests to assess the viability and metabolism of fibroblast and keratinocyte skin cells. Potential anti-aging properties were determined by their ability to inhibit the activity of the metalloproteinases collagenase and elastase. Tests showed that the extract and the ferment have antioxidant properties and stimulate the proliferation of both cell types. The study also assessed the anti-inflammatory activity of the extract and ferment by monitoring levels of the pro-inflammatory interleukins IL-6, IL-1ß, tumor necrosis factor (TNF-α) and anti-inflammatory IL-10 in lipopolysaccharide (LPS)-treated fibroblast cells. The results indicate that both the S. nigra extract and its kombucha ferment can be effective in preventing free-radical-induced cell damage and have positive effects on skin cell health.

Comparative Study of Cytotoxicity and Antioxidant, Anti-Aging and Antibacterial Properties of Unfermented and Fermented Extract of Cornus mas L.

Due to the high demand for products that can help treat various skin conditions, the interest in plant extracts, which are a valuable source of phytochemicals, is constantly growing. In this work, the properties of extracts and ferments from Cornus mas L. and their potential use in cosmetic products were compared. For this purpose, their composition, antioxidant properties and cytotoxicity against skin cells, keratinocytes and fibroblasts were assessed in vitro. In addition, the ability to inhibit the activity of collagenase and elastase was compared, which enabled the assessment of their potential to inhibit skin aging. Microbiological analyses carried out on different bacterial strains were made in order to compare their antibacterial properties. The conducted analyses showed that both dogwood extract and ferment have antioxidant and anti-aging properties. In addition, they can have a positive effect on the viability of keratinocytes and fibroblasts and inhibit the proliferation of various pathogenic bacteria, which indicates their great potential as ingredients in skin care preparations. The stronger activity of the ferment compared to the extract indicates the legitimacy of carrying out the fermentation process of plant raw materials using kombucha in order to obtain valuable products for the cosmetics industry.

Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation.

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr. Techniques such as thermal analysis, electron microscopy, spectroscopy and in vitro assays were used to characterize RocBr. A topical oil/water emulsion lotion formulation of RocBr was successfully developed and evaluated. The in vitro permeation behavior of RocBr from its lotion formulation was quantified with Strat-M® synthetic biomimetic membrane and EpiDerm™ 3D human skin tissue. Significant membrane retention of RocBr drug was evident and more retention was obtained with the lotion formulation compared with the solution. This is the first systematic and comprehensive study to report these findings.

Phytocannabinoids in the Pharmacotherapy of Psoriasis.

Phytocannabinoids are naturally occurring compounds, the main source of which is Cannabis sativa L. Through direct action or interaction with G protein-coupled receptors, they affect ROS and pro-inflammatory cytokines levels and modify the effectiveness of transcription factor responsible for the biosynthesis of antioxidants which lead to oxidative stress and its consequences. Due to the modification of the redox balance and inflammation, phytocannabinoids are used in the treatment of various diseases, including autoimmune dermatoses, such as atopic dermatitis and psoriasis. Psoriasis is one of the most common dermatoses, and one of unknown etiology. A disturbed redox balance with a shift towards the oxidation leads to oxidative stress, resulting in oxidative modifications, mainly of lipids and proteins, and prolonged activation of immune cells and increased generation of pro-inflammatory cytokines, resulting in chronic inflammation. Given the biological activity of phytocannabinoids, they have become the focus of research as components of pharmacotherapy for psoriasis. Beneficial effects were shown by various representatives of phytocannabinoids, but the effect of cannabidiol (CBD) on skin cells (in vitro and ex vivo) and on blood cells from patients with psoriasis vulgaris and psoriatic arthritis has been most often evaluated in recent years.

Evaluation of the Biological Activity of Hydrogel with Cornus mas L. Extract and Its Potential Use in Dermatology and Cosmetology.

Due to the growing popularity of herbal extract-loaded hydrogels, this study assessed the biological activity of extracts and hydrogels containing three types (water (WE), water-ethanol (EE) and water-glycerin (GE)) of Cornus mas L. (dogwood) extracts. The content of biologically active compounds in the extracts was assessed using the UPLC-DAD-MS technique. Antioxidant properties were assessed by using DPPH and ABTS radicals and measuring the intracellular level of reactive oxygen species. Alamar Blue and Neutral Red tests were used to measure the cytotoxicity of the tested samples on skin cells-fibroblasts and keratinocytes. Cell migration and the anti-aging activity of the tested extracts and hydrogels were assessed. Transepidermal water loss and skin hydration after applying the hydrogels to the skin were also determined. A chromatographic analysis revealed that the extracts contained polyphenols, including gallic, caftaric, protocatechuic, chlorogenic, ellagic and p-coumaroylquinic acids, as well as iridoids, with loganic acid as the predominant component. Additionally, they contained cyanidin 3-O-galactoside, pelargonidin 3-O-glucoside and quinic acid. The obtained results show that the tested extracts and hydrogels had strong antioxidant properties and had a positive effect on the viability of skin cells in vitro. Additionally, it was shown that they stimulated the migration of these cells and had the ability to inhibit the activity of collagenase and elastase. Moreover, the tested hydrogels increased skin hydration and prevented transepidermal water loss. The obtained results indicate that the developed hydrogels may be effective delivery systems for phytochemicals contained in dogwood extracts.

Glycolipid Biosurfactants in Skincare Applications: Challenges and Recommendations for Future Exploitation.

The 21st century has seen a substantial increase in the industrial applications of glycolipid biosurfactant technology. The market value of the glycolipid class of molecules, sophorolipids, was estimated to be USD 409.84 million in 2021, with that of rhamnolipid molecules projected to reach USD 2.7 billion by 2026. In the skincare industry, sophorolipid and rhamnolipid biosurfactants have demonstrated the potential to offer a natural, sustainable, and skin-compatible alternative to synthetically derived surfactant compounds. However, there are still many barriers to the wide-scale market adoption of glycolipid technology. These barriers include low product yield (particularly for rhamnolipids) and potential pathogenicity of some native glycolipid-producing microorganisms. Additionally, the use of impure preparations and/or poorly characterised congeners as well as low-throughput methodologies in the safety and bioactivity assessment of sophorolipids and rhamnolipids challenges their increased utilisation in both academic research and skincare applications. This review considers the current trend towards the utilisation of sophorolipid and rhamnolipid biosurfactants as substitutes to synthetically derived surfactant molecules in skincare applications, the challenges associated with their application, and relevant solutions proposed by the biotechnology industry. In addition, we recommend experimental techniques/methodologies, which, if employed, could contribute significantly to increasing the acceptance of glycolipid biosurfactants for use in skincare applications while maintaining consistency in biosurfactant research outputs.

Subchronic Graphene Exposure Reshapes Skin Cell Metabolism.

In recent years, the toxicity of graphene-related materials (GRMs) has been evaluated in diverse models to guarantee their safety. In most applications, sublethal doses of GRMs contact human barriers such as skin in a subchronic way. Herein, the subchronic effect (30 day exposure) of three GRMs (GO 1, GO 2, and FLG) with different oxidation degrees and sizes was studied. The effects of these materials on human skin cells, HaCaTs, were assayed through high-throughput metabolic-based readout and other cell-based assays. A differential effect was found between the different GRMs. GO 2 induced a metabolic remodeling in epithelial cells, increasing the level of tricarboxylic acid components, mirrored by increased cell proliferation and changes in cell phenotype. The oxidation degree, size, and method of manufacture of GRMs dictated harmful effects on cell metabolism and behavior generated by nontoxic exposures. Therefore, a "safe by design" procedure is necessary when working with these nanomaterials.