Dermis Of Skin Research Articles

Influence of type of vehicle on dermal penetration efficacy of hydrophilic, amphiphilic, lipophilic model drugs

The influence of the vehicle on the dermal penetration efficacy of three different active ingredient (AI) surrogates (hydrophilic, amphiphilic, lipophilic model drugs), that were incorporated into these vehicles, was investigated with the ex vivo porcine ear model, which allowed to assess time and space resolved dermal penetration profiles of the AI. Fifteen different vehicles, including classical vehicles (hydrogel, oleogel, o/w cream, w/o ointment, amphiphilic cream) and innovative vehicles were included into the study. Results show tremendous differences in the penetration efficacy of the AI among the different vehicles. The differences in the total amounts of penetrated AI between lowest and highest penetration were about 3-fold for the hydrophilic AI surrogate, 3.5-fold for the amphiphilic AI and almost 5-fold for the lipophilic AI. The penetration depth was also affected by the type of vehicle. Some vehicles allowed the AI to penetrate only into the upper layers of the stratum corneum, whereas others allowed the penetration of the AI into deeper layers of the viable dermis. Data therefore demonstrate that the vehicles in compounding medications cannot be exchanged against each other randomly if a constant and safe medication is desired. The data obtained in the study provide first information on which types of vehicles are exchangeable and which types of vehicles can be used for enhanced dermal penetration of AI, thus providing a first base for a science-based selection of vehicles that can provide both, efficient dermal drug delivery and skin barrier function maintenance/strengthening at the same time.

Rapid eradication of vancomycin and methicillin-resistant Staphylococcus aureus by MDP1 antimicrobial peptide coated on photocrosslinkable chitosan hydrogel: in vitro antibacterial and in silico molecular docking studies.

Antibiotic resistance and weak bioavailability of antibiotics in the skin due to systemic administration leads to failure in eradication of vancomycin- and methicillin-resistant Staphylococcus aureus (VRSA and MRSA)-associated wound infections and subsequent septicemia and even death. Accordingly, this study aimed at designing a photocrosslinkable methacrylated chitosan (MECs) hydrogel coated by melittin-derived peptide 1 (MDP1) that integrated the antibacterial activity with the promising skin regenerative capacity of the hydrogel to eradicate bacteria by burst release strategy. The MECs was coated with MDP1 (MECs-MDP1), characterized, and the hydrogel-peptide interaction was evaluated by molecular docking. Antibacterial activities of MECs-MDP1 were evaluated against VRSA and MRSA bacteria and compared to MECs-vancomycin (MECs-vanco). Antibiofilm activity of MECs-MDP1 was studied by our novel 'in situ biofilm inhibition zone (IBIZ)' assay, and SEM. Biocompatibility with human dermal fibroblast cells (HDFs) was also evaluated. Molecular docking showed hydrogen bonds as the most interactions between MDP1 and MECs at a reasonable affinity. MECs-MDP1 eradicated the bacteria rapidly by burst release strategy whereas MECs-vanco failed to eradicate them at the same time intervals. Antibiofilm activity of MECs-MDP1 were also proved successfully. As a novel report, molecular docking analysis has demonstrated that MDP1 covers the structure of MECs and also binds to lysozyme with a reasonable affinity, which may explain the inhibition of lysozyme. MECs-MDP1 was also biocompatible with human dermal fibroblast skin cells, which indicates its safe future application. The antibacterial properties of a photocrosslinkable methacrylated chitosan-based hydrogel coated with MDP1 antimicrobial peptide were successfully proved against the most challenging antibiotic-resistant bacteria causing nosocomial wound infections; VRSA and MRSA. Molecular docking analysis revealed that MDP1 interacts with MECs mainly through hydrogen bonds with reasonable binding affinity. MECs-MDP1 hydrogels eradicated the planktonic state of bacteria by burst release of MDP1 in just a few hours whereas MECs-vanco failed to eradicate them. inhibition zone assay showed the anti-biofilm activity of the MECs-MDP1 hydrogel too. These findings emphasize that MECs-MDP1 hydrogel would be suggested as a biocompatible wound-dressing candidate with considerable and rapid antibacterial activities to prevent/eradicate VRSA/MRSA bacterial wound infections.

Developing Plant Exosomes as an Advanced Delivery System for Cosmetic Peptide.

Peptides are a promising skincare ingredient, but due to their inherent instability and the barrier function of the skin's surface, they often have limited skin absorption and penetration, which can significantly hinder their skincare benefits. To address this, a novel technique called NanoGlow has been introduced for encapsulating peptide-based cosmetic raw materials into engineered nanosized plant-derived exosomes (pExo) to achieve the goal of a healthier and more radiant skin state. In this approach, pExo served as carriers for cosmetic peptides across the intact skin barrier, enhancing their biological effectiveness in skin beauty. The NanoGlow strategy combines chemical activation and physical proencapsulation, boasting a high success rate and straightforward and stable operation, making it suitable for large-scale production. Comprehensive analysis using in vitro cellular absorption and skin penetration models has demonstrated that the nanosized pExo carriers significantly improve peptide penetration into the skin compared to free peptides. Furthermore, in vivo tissue slice studies have shown that pExo carriers efficiently deliver acetyl hexapeptide-8 to the skin's dermis, surpassing the performance of free peptides. Cosmetic skincare effect analysis has also indicated that pExo-loaded cosmetic peptides deliver superior results. Therefore, the NanoGlow technique harnesses the natural size and properties of pExo to maximize the bioavailability of cosmetic peptides, holding great promise for developing advanced peptide delivery systems in both the cosmetic and medical drug industries.

Effect of poly-L-lactic acid and polydioxanone biostimulators on type I and III collagen biosynthesis.

Safe, effective, and biocompatible minimally invasive procedures with the potential to stimulate collagen production have been made to recover dermal thickness and skin quality. The main of this animal model experiment was to observe the effect of poly-L-lactic acid (PLLA) and polydioxanone (PDO) biostimulators in collagen I and III after hypodermal injection. Sixteen adult female rats (Wistar) were randomized into four groups and had dorsal treatment with: G1: hypodermic subcision (HS) only; G2: HS and PLLA hypodermic injection (HI), G3: HS and PDO HI; G4: Control, with no treatment. In histochemical, it was observed hypodermal and dermal tissue in more organized thickness in G3 and in G4 when compared to G1 and G2. There was few difference in G1 compared to G4. The tissue of G2 showed irregularities in the arrangement of collagen fibers, less defined structure and lower distribution of type I collagen compared to the other groups. There is a greater tendency for the proportions of type III collagen among tissues treated with both biostimulators (G2 and G3). PLLA and PDO had relatively similar percentages of collagen when compared to G4. The amount of type I collagen was higher in tissues treated with subcision, while type III collagen was higher in tissues treated with both biostimulators. G3 showed better performance in collagen production, although small, when compared with G2.

Biomimetic tri-layered artificial skin comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing

Full-thickness wounds are severe cutaneous damages with destroyed self-healing function, which need efficient clinical interventions. Inspired by the hierarchical structure of natural skin, we have for the first time developed a biomimetic tri-layered artificial skin (TLAS) comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing. The TLAS with the thickness of 3–7 mm displays a hierarchical nanostructure consisting of the top homogeneous silica gel film, the middle compact collagen membrane, and the bottom porous collagen scaffold, exquisitely mimicking the epidermis, basement membrane and dermis of natural skin, respectively. The 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide-dehydrothermal (EDC/NHS-DHT) dual-crosslinked collagen composite bilayer, with a crosslinking degree of 79.5 %, displays remarkable biocompatibility, bioactivity, and biosafety with no risk of hemolysis and pyrogen reactions. Notably, the extra collagen membrane layer provides a robust barrier to block the penetration of silica gel into the collagen porous scaffold, leading to the TLAS with enhanced biocompatibility and bioactivity. The full-thickness wound rat model studies have indicated the TLAS significantly facilitates the regeneration of full-thickness defects by accelerating re-epithelization, collagen deposition and migration of skin appendages. The highly biocompatible and bioactive tri-layered artificial skin provides an improved treatment for full-thickness wounds, which has great potential in tissue engineering.

Anti-skin aging effects and bioavailability of collagen tripeptide and elastin peptide formulations in young and middle-aged women

BackgroundCollagen peptides (CP), including tripeptides and elastin peptides (EP), are known for their in vitro and in vivo anti-skin aging effects. Despite positive results in animal models, the combination effects of CP and EP and the bioavailability of CP in human studies, particularly in young and middle-aged women, remain underexplored. ObjectiveTo evaluate the effects of an orally administered collagen drink combining CP and EP on the skin health of young and middle-aged women. Materials and MethodsA single-center, randomized, double-blind, parallel-controlled trial was conducted, utilizing the WONDERLAB® fish collagen tripeptide beverage. Participants consumed the drink over an 8-week period. ResultsCompared to the placebo group, the collagen drink group showed significant improvements in skin hydration (39.19% increase), transepidermal water loss (33.45% decrease), skin elasticity (25.37% increase), dermal collagen content (21.64% increase), pore size (7.94% decrease), wrinkle length (18.09% decrease), skin smoothness (2.85% improvement), and skin roughness (15.32% decrease). Overall pore volume decreased by 60%, and visual assessments indicated a decrease in skin luminosity by 15.20% and smoothness index by 22.55%. Mass spectrometry demonstrated a significant increase in collagen efficacy components, including blood pH and GPH levels (P < 0.05). ConclusionThe study confirmed the combination nourishing and anti-skin aging effects of EP and CP on the skin of young and middle-aged women, demonstrating significant improvements in various skin parameters and good bioavailability of collagen peptides.

Structural and ultrastructural aspects of the skin of large yellow croaker Larimichthys crocea.

The skin color of the large yellow croaker (Larimichthys crocea) is a crucial indicator to determine its economic value. However, the location of pigment cells in the skin structure is uncertain. To determine the pigment cell type in the skin, the vertical order and ultrastructure of pigment cells were examined using light microscopy and transmission electron microscopy. Both dorsal and ventral skins comprise the epidermis, dermis, and hypodermis. Xanthophores, melanophores, and iridophores were observed in the dermis of the dorsal skin, whereas the latter two were in the dermis of the ventral skin. Interestingly, the size of xanthophores in the dorsal skin was significantly smaller than that of xanthophores in the ventral skin; however, the density of dorsal xanthophores was significantly higher than that of ventral xanthophores. The type L-iridophores with large crystalline structures were observed in the uppermost area of the upper pigment layer, which contributed to the strikingly metallic luster shown by the ventral skin. The melanophores were exclusively found in the dorsal skin, offering the purpose of camouflage. Taken together, our results indicated that the pigment cells display different arrangement patterns between dorsal and ventral skin, and the golden color in the ventral skin results from the coexistence of light-reflecting iridophores and light-absorbing xanthophores.

Fabrication and In-Vivo Evaluation of Polyvinyl pyrrolidone/Poloxamer 188 Hybrid Nanofibers of Deflazacort

The superior flexibility, efficient drug loading, high surface-to-volume ratio, ease of formulation, and cost-controlled production are considered exceptional advantages of nanofibers (NFs) as a smart delivery system. Deflazacort (DEF) is an anti-inflammatory and immunosuppressant agent. It is categorized as a poorly soluble class II drug. In this study, DEF-loaded polymeric nanofibrous using the electrospinning technique mats, Polyvinyl pyrrolidone (PVP) with or without Poloxamer 188 (PX) were used as mat-forming polymers. Microscopical imaging, drug content (%), and in vitro dissolution studies were conducted for all NFs formulae (F1-F7). All NFs improved the DEF dissolution compared to the unprocessed form, with the superiority of the PVP/PX hybrid. The optimized formula (F7) exhibited an average diameter of 655.46 ± 90.4 nm and % drug content of 84.33 ± 5.58. The dissolution parameters of DEF loaded in PVP/PX NFs (F7) reflected a release of 95.3 % ± 3.1 and 102.6 % ± 1.7 after 5 and 60 min, respectively. NFs (F7) was investigated for drug-polymer compatibility using Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-ray diffraction analysis (PXRD), and Differential Scanning Calorimetry (DSC). In vivo anti-inflammatory study employing male Sprague-Dawley rats showed a significant reduction of rat paw edema for F7 (p < 0.05) compared with unprocessed DEF with a normal epidermal and dermal skin structure comparable to the healthy negative control. Immunohistochemical and morphometric data displayed similarities between the immune reaction of F7 and the negative healthy control. The finding of this work emphasized that DEF loaded in PVP/PX NFs could be considered a useful strategy for enhancing the therapeutic performance of DEF.

Evaluation of the efficacy of mesenchymal stem cells derived conditioned medium in the treatment of striae distensae: a double blind randomized clinical trial

BackgroundStriae distensae is a disfiguring atrophic skin condition that impairs the body’s aesthetic image. Despite the variety of conducted studies, there is controversy regarding the best modalities. Human mesenchymal stem cells are considered a rich source for scar treatment. Skin needling is among the most efficient and safe aesthetic and therapeutic devices. This study aimed to evaluate the efficacy of the combination of needling and intradermal injection of mesenchymal stem cells compared to skin needling alone for treating striae distensae.MethodThis study was a randomized, double-blind clinical trial involving 10 women aged 18–60. Each striae lesion was divided into two parts, with one side receiving needling and intradermal injection of conditioned medium, while the other side received needling and intradermal injection of normal saline. This treatment was administered in three sessions with three-week intervals. Patients were evaluated before the first intervention and three months after the final session. Three months after the completion of the intervention, patients’ lesions were evaluated using biometric criteria, physician evaluation, and patient self-assessment.ResultsThe results demonstrated a significant improvement in dermal and complete thickness and skin density in patients treated with microneedling. All skin ultrasound parameters improved significantly in patients receiving the combination of needling and conditioned medium. When comparing the two groups, significantly higher physician and patient satisfaction was observed in the combination group. However, the comparison of biometric indices improvement wasn’t significant between these groups.ConclusionThe combination of human mesenchymal stem cells with microneedling could be considered a novel effective option for stretch marks.

Natural cellulosic biofunctional textiles from onion (Allium cepa L.) skin extracts: A sustainable strategy for skin protection

Cellulosic fabrics made of cotton, linen, bamboo, hemp, and nettle, were selected for the eco-sustainable production of colored biofunctional textiles, using natural dyes from onion skin of the Dorata di Parma (Allium cepa L.) variety. Dyeing experiments were performed in net water with and without pre-treatment with alum, tin chloride, and tannic acid as mordants. The color and the UV-protection factor (UPF) were evaluated through UV–visible spectroscopy. The treatment with onion skin extract induced a relevant increase of UPF in all investigated fabrics, promoting the protection category from insufficient (UPF<15) to good for linen (UPF = 21–26), up to very good and excellent for cotton (UPF = 35–66) and bamboo (UPF = 48–56), respectively. To mimic the direct contact with the skin, textile samples were immersed in artificial sweat where dyed cotton, hemp, and nettle were found to promote higher phenolic release (0.28–0.50 mg gallic acid equivalents/g textile) than linen and bamboo (0.12–0.22 mg gallic acid equivalents/g textile). The obtained “biofunctional sweat” did not impact on the survival of primary human dermal fibroblasts (HDF) and skin keratinocytes (NCTC2455), while protected these cells against heat shock and reduced reactive oxygen species levels upon exposure to pro-oxidant and inflammatory agents as H2O2 and lipopolysaccharide, respectively. Increased activity levels of the H2O2-scavenging enzyme Catalase (CAT) were also observed, thus demonstrating enhanced stress response and homeostatic capability of these cells. This study provides evidence that extracts from onion waste can be used to functionalize cellulosic fabrics conferring properties as natural shield against UV radiation, and antioxidant and anti-inflammatory materials thus holding potential in skin protection and prevention of dermatological diseases.

Skin boosters: Definitions and varied classifications.

The concept of "skin boosters" has evolved, marking a shift from traditional uses of hyaluronic acid (HA) fillers primarily for augmenting skin volume to a more diverse application aimed at improving dermal conditions. Restylane Vital and other HA fillers have been repurposed to combat skin aging and wrinkles by delivering HA directly to the dermis. This review aims to define the term "skin booster" and to discuss the various components that constitute skin boosters. It seeks to provide a comprehensive overview of the different ingredients used in skin boosters, their roles, and their impact on enhancing dermal conditions. A comprehensive review was conducted, focusing on representative skin booster ingredients. The approach involved analyzing the different elements used in skin boosters and their specific roles in enhancing dermal improvement. The findings indicate that skin boosters, encompassing a range of ingredients, are effective in improving the condition of the skin's dermis. The review identifies key ingredients in skin boosters and their specific benefits, including hydration, elasticity improvement, and wrinkle reduction. Skin boosters represent a significant development in dermatological treatments, offering diverse benefits beyond traditional HA fillers. This review provides valuable insights into the constituents of skin boosters and their effectiveness, aiding readers in making informed decisions about these treatments. The potential of skin boosters in dermatological practice is considerable, warranting further research and application.

Assessment of the anti-psoriasis effect of Scrophularia deserti methanolic extract in mice model

Psoriasis is an underestimated chronic and autoimmune skin disorder. Topical chemical agents are applied for psoriasis control and treatment, notwithstanding their subordinate efficiency or unsuccessful activities. As an alternative, herbal medicine can also be used in its treatment.&#x0D; The aim of the present study was performed to assess the anti-psoriasis effect of Scrophularia deserti in mice model.&#x0D; Materials and methods: S. deserti was purchased and used for methanolic extraction. Extract DPPH radical scavenging activity, polyphenol and flavonoid contents were examined. Sixty male mice were purchased, and psoriasis was induced using 10 days of topical administration of Imiquimod (62.5 mg). Mice were classified into 6 groups: non-psoriasis control (only received distilled water), psoriasis control (only received topical Imiquimod), two S. deserti treatments (topical 300 and 500 mg/kg), topical Betamethasone, and topical α-pinene 9 %. Cytokine distribution and histopathological properties were also determined.&#x0D; Results: the value at which the S. deserti methanolic extract scavenges 50 % of free radicals (IC50) was 602.71±15.33 µg/mL. The total S. deserti methanolic extract flavonoid and polyphenol contents were 16.85±1.12 mg QE/g and 58.47±3.25 mg GAE/g, respectively. IL-22, TNF-α, and IL-17A concentrations increased after psoriasis induction compared to the control group (P &lt;0.05). Mice treated with Betamethasone harboured the lowest concentrations of IL-22, TNF-α, and IL-17A (P &lt;0.05).&#x0D; Conclusions: Mice treated with S. deserti methanolic extract (500 mg/kg) also harboured significantly lower IL-22, TNF-α, and IL-17A (P &lt;0.05) compared to α-pinene and S. deserti methanolic extract (300 mg/kg). Mice of the psoriasis control group showed significant epidermis hyperkeratosis, acanthosis, and crust with plentiful inflammatory cells. At the same time, mice treated with S. deserti methanolic extract (500 mg/kg) showed significant recovered tissue with normal skin epidermis and dermis, sebaceous glands, and follicles of the hair, besides the lowest rate of inflammatory reactions. Findings showed that the S. deserti methanolic extract (500 mg/kg) can efficiently be used as a practical substitute for psoriasis treatment. However, some supplementary research should be performed

Research Trends on Atopic Dermatitis an Autoimmune Disease and Exercise

PURPOSE: Autoimmune diseases attack the organs and tissues of the body because of abnormalities in the immune system, causing health issues such as inflammation and atopic dermatitis. Atopic dermatitis is a chronic inflammatory skin disease with a multifactorial pathogenesis that presents with an itchy, dry dermis. Atopic dermatitis can be alleviated or worsened by environmental factors, and studies have reported that exercise has various effects on atopic dermatitis.METHODS: This review collected and analyzed data on the effects of exercise and atopic dermatitis from previous studies obtained through online databases and search engines, including PubMed, Web of Science, and Google Scholar.RESULTS: Moderate exercise has a positive effect on the health of patients with atopic dermatitis. During moderate- and high-intensity exercise, the thickness of the dermis and epidermis of atopic skin, serum immunoglobulin (Ig)E levels, and cytokine levels decreased. However, conflicting results showed that high-intensity swimming exercises increased the severity of atopic dermatitis. Additionally, patients with atopic dermatitis and lower physical activity levels showed increased disease severity.CONCLUSION: These results indicate that several exercises have therapeutic potential against atopic diseases. Further studies are required to investigate the effects of exercise on atopic dermatitis, including the limitations.

Biofabrication of biomimetic undulating microtopography at the dermal-epidermal junction and its effects on the growth and differentiation of epidermal cells.

The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells forin vitroculturing.In vitroresults showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, thesein vitrohuman epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.

The use of dermal templates in dermato-surgery and patient perspectives.

Acellular dermal matrices currently represent a useful reconstructive method in onco-dermatologic surgery. Nevertheless, they have some limitations, especially in terms of costs and outpatient post-operative wound care. While some studies on their cost-to-benefit ratio in breast surgery have already been issued, evidence is currently lacking in onco-dermatological surgery. The aim of this study was to evaluate the clinical outcomes perceived by patients who had undergone onco-dermatologic surgery in which either acellular dermal matrices or skin grafts had been used as reconstructive methods. A study population of 150 patients was identified retrospectively and patients' degree of satisfaction was assessed through the Global Aesthetic Improvement Scale and the Patient Scar Scale Questionnaire. Despite similar scores among the study groups, slightly better results were appreciable after single-stage grafting. However, to what extent these variations really represent a significant difference from a clinical point of view remains to be determined. Moreover, other potential bias in the interpretation of our results may reside in differences in terms of age, body location and baseline tumor size among the study groups. Therefore, further research is needed.

Simultaneous quantification of TB-500 and its metabolites in in-vitro experiments and rats by UHPLC-Q-Exactive orbitrap MS/MS and their screening by wound healing activities in-vitro

BackgroundTB-500 (Ac-LKKTETQ), derived from the active site of thymosin β4 (Tβ4), has various biological functions in its unacetylated form, LKKTETQ. These functions include actin binding, dermal wound healing, angiogenesis, and skin repair. The biological effects of TB-500, however, have not been documented. And the analysis of TB-500 and its metabolites have been neither simultaneously quantified nor structurally identified using synthesized authentic standards. MethodsThis study was aimed to investigating simultaneous analytical methods of TB-500 and its metabolites in in-vitro and urine samples by using UHPLC-Q-Exactive orbitrap MS, and to comparing the biological activity of its metabolites with the parent TB-500. The metabolism of TB-500 was investigated in human serum, various in-vitro enzyme systems, and urine samples from rats treated with TB-500, and their biological activities measured by cytotoxicity and wound healing experiments were also evaluated in fibroblasts. ResultsThe simultaneous analytical method for TB-500 and its metabolites was developed and validated. The study found that Ac-LK was the primary metabolite with the highest concentration in rats at 0–6 h intervals. Also, the metabolite Ac-LKK was a long-term metabolite of TB-500 detected up to 72 hr. No cytotoxicity of the parent and its metabolites was found. Ac-LKKTE only showed a significant wound healing activity compared to the control. ConclusionThe study provides a valuable tool for quantifying TB-500 and its metabolites, contributing to the understanding of metabolism and potential therapeutic applications. Our results also suggest that the previously reported wound-healing activity of TB-500 in literature may be due to its metabolite Ac-LKKTE rather than the parent form.

Uniaxial mechanical stretch properties correlated with three-dimensional microstructure of human dermal skin.

The intact and healthy skin forms a barrier to the outside world and protects the body from mechanical impact. The skin is a complex structure with unique mechano-elastic properties. To better direct the design of biomimetic materials and induce skin regeneration in wounds with optimal outcome, more insight is required in how the mechano-elastic properties emerge from the skin's main constituents, collagen and elastin fibers. Here, we employed two-photon excited autofluorescence and second harmonic generation microscopy to characterize collagen and elastin fibers in 3D in 24 human dermis skin samples. Through uniaxial stretching experiments, we derive uni-directional mechanical properties from resultant stress-strain curves, including the initial Young's modulus, elastic Young's modulus, maximal stress, and maximal and mid-strain values. The stress-strain curves show a large variation, with an average Young's modules in the toe and linear regions of 0.1 MPa and 21 MPa. We performed a comprehensive analysis of the correlation between the key mechanical properties with age and with microstructural parameters, e.g., fiber density, thickness, and orientation. Age was found to correlate negatively with Young's modulus and collagen density. Moreover, real-time monitoring during uniaxial stretching allowed us to observe changes in collagen and elastin alignment. Elastin fibers aligned significantly in both the heel and linear regions, and the collagen bundles engaged and oriented mainly in the linear region. This research advances our understanding of skin biomechanics and yields input for future first principles full modeling of skin tissue.

Lipid Peroxidation as the Mechanism Underlying Polycyclic Aromatic Hydrocarbons and Sunlight Synergistic Toxicity in Dermal Fibroblasts.

Light and atmospheric pollution are both independently implicated in cancer induction and premature aging. Evidence has been growing more recently on the toxic synergy between light and pollutants. Polycyclic aromatic hydrocarbons (PAHs) originate from the incomplete combustion of organic matter. Some PAHs, such as the Benzo[a]pyrene (BaP), absorb ultraviolet A (UVA) wavelengths and can act as exogenous chromophores, leading to synergistic toxicity through DNA damage and cytotoxicity concomitant to ROS formation. In this study, we shed light on the mechanism underlying the toxic synergy between PAHs and UVA. Using dermal fibroblasts co-exposed to UVA and BaP, we have demonstrated that the photosensitization reaction causes mortality, which is most likely caused by ROS accumulation. We have shown that these ROS are concentrated in the lipids, which causes an important induction of lipid peroxidation and malondialdehyde, by-products of lipid peroxidation. We have also shown the accumulation of bulky DNA damage, most likely generated by these by-products of lipid peroxidation. To our knowledge, this study represents the first one depicting the molecular effects of photo-pollution on dermal skin.

Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization.

Fibroblasts are the most abundant cell type in dermal skin and keratinocytes are the most abundant cell type in the epidermis; both play a crucial role in wound remodeling and maturation. We aim to assess the functionality of a novel dual gene activated scaffold (GAS) on human adult dermal fibroblasts (hDFs) and see how the secretome produced could affect human dermal microvascular endothelial cells (HDMVECs) and human epidermal keratinocyte (hEKs) growth and epithelization. Our GAS is a collagen chondroitin sulfate scaffold loaded with pro-angiogenic stromal derived factor (SDF-1α) and/or an anti-aging β-Klotho plasmids. hDFs were grown on GAS for two weeks and compared to gene-free scaffolds. GAS produced a significantly better healing outcome in the fibroblasts than in the gene-free scaffold group. Among the GAS groups, the dual GAS induced the most potent pro-regenerative maturation in fibroblasts with a downregulation in proliferation (twofold, p < 0.05), fibrotic remodeling regulators TGF-β1 (1.43-fold, p < 0.01) and CTGF (1.4-fold, p < 0.05), fibrotic cellular protein α-SMA (twofold, p < 0.05), and fibronectin matrix deposition (twofold, p < 0.05). The dual GAS secretome also showed enhancements of paracrine keratinocyte pro-epithelializing ability (1.3-fold, p < 0.05); basement membrane regeneration through laminin (6.4-fold, p < 0.005) and collagen IV (8.7-fold, p < 0.005) deposition. Our findings demonstrate enhanced responses in dual GAS containing hDFs by proangiogenic SDF-1α and β-Klotho anti-fibrotic rejuvenating activities. This was demonstrated by activating hDFs on dual GAS to become anti-fibrotic in nature while eliciting wound repair basement membrane proteins; enhancing a proangiogenic HDMVECs paracrine signaling and greater epithelisation of hEKs.

Personal Hygene Dengan Kejadian Dermatitis Di Desa Haria Kecamatan Saparua Maluku Tengah Tahun 2021

Dermatitis is inflammation of the skin (epidermis and dermis) as a responder to the influence of oxygen factors and / or endpgen factors, causing clinical abnormalities in the form of inflorescences, polymorphics and itchy complaints. Personal hygiene is a rare or act of maintaining personal hygiene and physical and mental health, personal protective equipment is an effort to prevent dermatitis, because using personal protective equipment can avoid direct contact with chemicals. This study is to determine the relationship between personal hygiene and the use of personal protective equipment with the incidence of dermatitis in traditional fishermen in Haria Village, Saparua District, Central Maluku Regency. This research is a type of quantitative research with an approach using a sectional cros design. The sampling technique used is using the total sampling technique, which is a sampling technique when members of all populations are used as samples, the measuring instrument used is a questionnaire. Data analysis using univariate and bivariate analysis using chi-square test. This study showed a relationship between personal hygiene with the incidence of dermatitis (p-value = 0.04) and the use of personal protective equipment with the incidence of dermatitis (p-value = 0.03). The conclusion is that there is a relationship between pesonal hygiene, the use of personal protective equipment with the incidence of dermatitis, fishermen's advice to pay more attention to personal hygiene and use protective equipment.