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1.
Eur J Pharm Sci ; 203: 106925, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39374744

ABSTRACT

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70 % of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1 %, remaining stable for 8 h. Drug content decreased to ∼80 % after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70 % of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.


Subject(s)
Administration, Cutaneous , Dexamethasone , Hydrogen Sulfide , Skin , Hydrogen Sulfide/administration & dosage , Hydrogen Sulfide/chemistry , Dexamethasone/administration & dosage , Dexamethasone/chemistry , Animals , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Nanostructures/administration & dosage , Nanostructures/chemistry , Drug Delivery Systems/methods , Humans , Psoriasis/drug therapy , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry
2.
J Biomed Mater Res B Appl Biomater ; 112(10): e35485, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39324392

ABSTRACT

The development of new wound dressings made from biomaterials, which offer a better cost-benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%-4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.


Subject(s)
Chitosan , Hyaluronic Acid , Membranes, Artificial , Skin , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Animals , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Wound Healing/drug effects , Rats , Skin/injuries , Skin/metabolism , Male , Rats, Wistar , Bandages
3.
Int J Mol Sci ; 25(17)2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39273169

ABSTRACT

Parkinson's disease (PD) is a multifactorial, chronic, and progressive neurodegenerative disorder inducing movement alterations as a result of the loss of dopaminergic (DAergic) neurons of the pars compacta in the substantia nigra and protein aggregates of alpha synuclein (α-Syn). Although its etiopathology agent has not yet been clearly established, environmental and genetic factors have been suggested as the major contributors to the disease. Mutations in the glucosidase beta acid 1 (GBA1) gene, which encodes the lysosomal glucosylceramidase (GCase) enzyme, are one of the major genetic risks for PD. We found that the GBA1 K198E fibroblasts but not WT fibroblasts showed reduced catalytic activity of heterozygous mutant GCase by -70% but its expression levels increased by 3.68-fold; increased the acidification of autophagy vacuoles (e.g., autophagosomes, lysosomes, and autolysosomes) by +1600%; augmented the expression of autophagosome protein Beclin-1 (+133%) and LC3-II (+750%), and lysosomal-autophagosome fusion protein LAMP-2 (+107%); increased the accumulation of lysosomes (+400%); decreased the mitochondrial membrane potential (∆Ψm) by -19% but the expression of Parkin protein remained unperturbed; increased the oxidized DJ-1Cys106-SOH by +900%, as evidence of oxidative stress; increased phosphorylated LRRK2 at Ser935 (+1050%) along with phosphorylated α-synuclein (α-Syn) at pathological residue Ser129 (+1200%); increased the executer apoptotic protein caspase 3 (cleaved caspase 3) by +733%. Although exposure of WT fibroblasts to environmental neutoxin rotenone (ROT, 1 µM) exacerbated the autophagy-lysosomal system, oxidative stress, and apoptosis markers, ROT moderately increased those markers in GBA1 K198E fibroblasts. We concluded that the K198E mutation endogenously primes skin fibroblasts toward autophagy dysfunction, OS, and apoptosis. Our findings suggest that the GBA1 K198E fibroblasts are biochemically and molecularly equivalent to the response of WT GBA1 fibroblasts exposed to ROT.


Subject(s)
Apoptosis , Autophagy , Fibroblasts , Glucosylceramidase , Mitochondria , Oxidative Stress , Glucosylceramidase/metabolism , Glucosylceramidase/genetics , Humans , Fibroblasts/metabolism , Autophagy/genetics , Mitochondria/metabolism , Parkinson Disease/metabolism , Parkinson Disease/genetics , Parkinson Disease/pathology , Skin/metabolism , Skin/pathology , Lysosomes/metabolism , alpha-Synuclein/metabolism , alpha-Synuclein/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Mutation
4.
Int J Mol Sci ; 25(18)2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39337510

ABSTRACT

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.


Subject(s)
Chondroitin Sulfates , Nanoparticles , Chondroitin Sulfates/chemistry , Animals , Swine , Nanoparticles/chemistry , Regeneration/drug effects , Cartilage/drug effects , Cartilage/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/pathology , Cell Survival/drug effects , Humans , Administration, Topical , Nanostructures/chemistry , Drug Carriers/chemistry , Drug Delivery Systems/methods , Skin/drug effects , Skin/metabolism
5.
AAPS PharmSciTech ; 25(7): 212, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39242428

ABSTRACT

UV radiation causes long- and short-term skin damage, such as erythema and skin cancer. Therefore, the use of sunscreens is extremely important. However, concerns about UV filter safety have prompted exploration into alternative solutions, with nanotechnology emerging as a promising avenue. This systematic review identified 23 experimental studies utilizing nanocarriers to encapsulate sunscreens with the aim of enhancing their efficacy and safety. Polymeric and lipid nanoparticles are frequently employed to encapsulate both organic and inorganic UV filters along with natural antioxidants. Nanocarriers have demonstrated benefits including reduced active ingredient usage, increased sun protection factor, and mitigated photoinstability. Notably, they also decreased the skin absorption of UV filters. In summary, nanocarriers represent a viable strategy for improving sunscreen formulations, offering enhanced physicochemical properties and bolstered photoprotective effects, thereby addressing concerns regarding UV filter safety and efficacy in cosmetic applications.


Subject(s)
Nanoparticles , Nanotechnology , Sunscreening Agents , Ultraviolet Rays , Animals , Humans , Antioxidants/administration & dosage , Antioxidants/chemistry , Antioxidants/pharmacology , Drug Carriers/chemistry , Lipids/chemistry , Nanoparticles/chemistry , Nanotechnology/methods , Polymers/chemistry , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Sun Protection Factor , Sunscreening Agents/chemistry , Sunscreening Agents/administration & dosage , Ultraviolet Rays/adverse effects
6.
Int J Pharm ; 665: 124730, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39299356

ABSTRACT

Dacarbazine (DTIC) is the drug of choice for melanoma treatment, but its systemic administration is related to several adverse effects. Here, DTIC topical delivery stimulated by iontophoresis is proposed to overcome such drawbacks. Hence, this work analyzed the impact of anodal iontophoresis on DTIC cutaneous delivery to provide an innovative topical alternative for melanoma treatment. The electrical stability of the drug was evaluated prior to the iontophoretic experiments, which demonstrated the need to add an antioxidant to the drug formulation. DTIC cutaneous permeation was evaluated in vitro for 6 h using three current densities (0.10, 0.25, and 0.50 mA/cm2). In addition, the effect of DTIC against skin cancer cells (MeWo and WM164) was investigated for 72 h of exposure to the drug. Iontophoresis stimulated skin drug permeation compared to the passive control. However, the antioxidant presence reduced DTIC permeation under the lower currents of 0.10 and 0.25 mA/cm2, which was compensated by increasing the current density to 0.50 mA/cm2. At 0.50 mA/cm2, iontophoresis enhanced topical cutaneous drug permeation 7-fold (p < 0.05) compared to the passive control. DTIC showed a concentration-dependent antiproliferative effect on melanoma cell lines. Thus, iontophoresis intensifies DTIC skin penetration in concentrations that can reduce cell viability and induce cell death. In conclusion, DTIC cutaneous delivery mediated by iontophoresis is a promising approach for treating melanomas and other skin tumors.


Subject(s)
Administration, Cutaneous , Dacarbazine , Iontophoresis , Melanoma , Skin Absorption , Skin Neoplasms , Iontophoresis/methods , Melanoma/drug therapy , Humans , Skin Neoplasms/drug therapy , Cell Line, Tumor , Dacarbazine/administration & dosage , Dacarbazine/pharmacokinetics , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/pharmacokinetics , Cell Survival/drug effects , Skin/metabolism , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Drug Delivery Systems
7.
Lasers Med Sci ; 39(1): 230, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39222167

ABSTRACT

The aim of the present study was to evaluate the photothermal effects of a subdermal high-power diode laser at a wavelength (λ) of 1470 nm in the skin of rats. Twenty male Wistar rats were used, divided into 2 groups: placebo laser (PL) and active laser (AL). A high-power diode laser equipment was applied to 5 subdermal vectors on the animal's back region. The results demonstrated that active laser animals showed a better arrangement of collagen fiber bands, an increase in the thickness of the dermis and the number of vessels. Furthermore, animals treated with active laser showed an increased immunoexpression of TGF-ß and VEGF compared to the placebo. The present work demonstrated that the subdermal high-power diode laser increases the vascularization and the expression of factors that enhance skin regeneration and may be promising resource in the esthetic and dermatology clinical treatment of skin rejuvenation.


Subject(s)
Lasers, Semiconductor , Rats, Wistar , Skin , Animals , Male , Rats , Lasers, Semiconductor/therapeutic use , Skin/radiation effects , Skin/metabolism , Vascular Endothelial Growth Factor A/metabolism , Transforming Growth Factor beta/metabolism , Rejuvenation , Models, Animal
8.
J Bras Nefrol ; 46(4): e20240047, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-39186633

ABSTRACT

The accumulation of advanced glycation end-products (AGEs) elicits morphofunctional kidney impairment. AGEs levels can be noninvasively estimated by skin autofluorescence (SAF). We explored whether high SAF predicts kidney outcomes in type 2 diabetes (T2D) individuals. The study was conducted as a predefined analysis of the Brazilian Diabetes Study, a prospective single-center cohort of T2D adults. Data from 155 individuals followed for up to 1716 days were considered. The incidence of major adverse kidney events (MAKE) was 9.6%. Individuals with above-median SAF had a higher incidence of MAKEs (4.6% vs. 21%; p = 0.002), with an HR of 3.39 [95% CI: 1.06-10.85; p = 0.040] after adjustment by age and gender. The mean adjusted eGFR change was 1.08 units (SE: 1.15; 95%CI: -1.20, 3.37) in the low SAF and -5.19 units [SE: 1.93; 95%CI: -9.10, -1.29] in the high SAF groups (between-subject difference: F: 5.62, p = 0.019). The high-SAF group had a greater prevalence of rapid decliners than the low-SAF group (36.7% vs. 15.8%; p = 0.028). In conclusion, high SAF was related to increased incidence of MAKEs and faster decline in eGFR among T2D subjects. This should be considered by healthcare providers when identifying individuals more prone to diabetes-related kidney complications.


Subject(s)
Diabetes Mellitus, Type 2 , Glycation End Products, Advanced , Skin , Humans , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/complications , Male , Female , Glycation End Products, Advanced/metabolism , Glycation End Products, Advanced/analysis , Brazil/epidemiology , Middle Aged , Prospective Studies , Skin/metabolism , Skin/chemistry , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Aged , Prognosis
9.
J Proteome Res ; 23(10): 4273-4285, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39024464

ABSTRACT

Petroleum-derived substances, like industrial oils and grease, are ubiquitous in our daily lives. Comprised of petroleum hydrocarbons (PH), these substances can come into contact with our skin, potentially causing molecular disruptions and contributing to the development of chronic disease. In this pilot study, we employed mass spectrometry-based untargeted metabolomics and 16S rRNA gene sequencing analyses to explore these effects. Superficial skin samples were collected from subjects with and without chronic dermal exposure to PH at two anatomical sites: the fingers (referred to as the hand) and arms (serving as an intersubject variability control). Exposed hands exhibited higher bacterial diversity (Shannon and Simpson indices) and an enrichment of oil-degrading bacteria (ODB), including Dietzia, Paracoccus, and Kocuria. Functional prediction suggested enriched pathways associated with PH degradation in exposed hands vs non-exposed hands, while no differences were observed when comparing the arms. Furthermore, carboxylic acids, glycerophospholipids, organooxygen compounds, phenol ethers, among others, were found to be more abundant in exposed hands. We observed positive correlations among multiple ODB and xenobiotics, suggesting a chemical remodeling of the skin favorable for ODB thriving. Overall, our study offers insights into the complex dysregulation of bacterial communities and the chemical milieu induced by chronic dermal exposure to PH.


Subject(s)
Hydrocarbons , Metabolome , Microbiota , Petroleum , Skin , Humans , Pilot Projects , Petroleum/toxicity , Petroleum/metabolism , Skin/microbiology , Skin/metabolism , Skin/drug effects , Microbiota/drug effects , Metabolome/drug effects , Hydrocarbons/metabolism , Adult , Male , Female , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Bacteria/classification , Bacteria/metabolism , Bacteria/drug effects , Middle Aged
10.
Photodermatol Photoimmunol Photomed ; 40(4): e12990, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39031566

ABSTRACT

BACKGROUND: Wound healing is a multistep process involving coordinated responses of a variety of cell types, cytokines, growth factors, and extracellular matrix (ECM) components leading to the physiological restoration of tissue integrity. Photobiomodulation therapy (PBMT) has been highlighted as an approach to improve the healing process, nonetheless at the molecular level, the effects of PBMT are not entirely understood. AIM: To systematically review publications that investigated gene expression after PBMT during in vivo skin repair. METHODS: An electronic search was undertaken in Medline Ovid (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), Embase, and LILACS databases. The search strategy was conducted from the terms: low-level light therapy, gene expression, and wound healing and their synonyms. The databases were consulted in December 2023 and no publication year limit was used. RESULTS: Eleven studies were included in this review and the expression of 186 genes was evaluated. PBMT modified the expression of several targets genes studied, such as down-regulation of genes related to extracellular matrix proteases (MMP2 and MMP9) and pro-inflammatory cytokines (IL10 and IL6) and up-regulation of DNMT3A and BFGF. CONCLUSION: This review demonstrates that PBMT is capable of regulating gene expression during wound healing. Most evidence showed a positive impact of PBMT in regulating genes linked to inflammatory cytokines improving skin wound healing. Yet, the effects of PBMT in genes involved in other mechanisms still need to be better understood.


Subject(s)
Low-Level Light Therapy , Skin , Wound Healing , Animals , Humans , Cytokines/metabolism , Gene Expression/radiation effects , Gene Expression Regulation/radiation effects , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Skin/metabolism , Skin/radiation effects , Skin/pathology , Skin/injuries , Wound Healing/radiation effects
11.
Int J Mol Sci ; 25(13)2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38999961

ABSTRACT

Skin wound healing is coordinated by a delicate balance between proinflammatory and anti-inflammatory responses, which can be affected by opportunistic pathogens and metabolic or vascular diseases. Several antimicrobial peptides (AMPs) possess immunomodulatory properties, suggesting their potential to support skin wound healing. Here, we evaluated the proregenerative activity of three recently described AMPs (Clavanin A, Clavanin-MO, and Mastoparan-MO). Human primary dermal fibroblasts (hFibs) were used to determine peptide toxicity and their capacity to induce cell proliferation and migration. Furthermore, mRNA analysis was used to investigate the modulation of genes associated with skin regeneration. Subsequently, the regenerative potential of the peptides was further confirmed using an ex vivo organotypic model of human skin (hOSEC)-based lesion. Our results indicate that the three molecules evaluated in this study have regenerative potential at nontoxic doses (i.e., 200 µM for Clavanin-A and Clavanin-MO, and 6.25 µM for Mastoparan-MO). At these concentrations, all peptides promoted the proliferation and migration of hFibs during in vitro assays. Such processes were accompanied by gene expression signatures related to skin regenerative processes, including significantly higher KI67, HAS2 and CXCR4 mRNA levels induced by Clavanin A and Mastoparan-MO. Such findings translated into significantly accelerated wound healing promoted by both Clavanin A and Mastoparan-MO in hOSEC-based lesions. Overall, the data demonstrate the proregenerative properties of these peptides using human experimental skin models, with Mastoparan-MO and Clavanin A showing much greater potential for inducing wound healing compared to Clavanin-MO.


Subject(s)
Cell Movement , Cell Proliferation , Fibroblasts , Regeneration , Skin , Wound Healing , Humans , Wound Healing/drug effects , Skin/metabolism , Skin/drug effects , Cell Proliferation/drug effects , Cell Movement/drug effects , Fibroblasts/drug effects , Fibroblasts/metabolism , Regeneration/drug effects , Intercellular Signaling Peptides and Proteins/metabolism , Antimicrobial Peptides/pharmacology , Cells, Cultured , Peptides/pharmacology
12.
Arch Anim Nutr ; 78(2): 159-177, 2024 Apr.
Article in English | MEDLINE | ID: mdl-39037852

ABSTRACT

Black soldier fly meal in pet diets is gaining acceptance. This study aimed to assess the use of black soldier fly larvae defatted meal (BSFL) and its impact on blood parameters, biochemical markers, organic antioxidant capacity, skin barrier function and skin and coat quality. A cross-over study involved eight beagle dogs with two periods of 50 days each and a washout period of seven days in between. Two approximately iso-nutritive extruded diets were evaluated, the first containing 29.5% BSFL meal and a control diet containing 26% poultry by-product meal (PBP) as protein source. Skin and coat evaluations and blood collections were conducted before and after each period. Skin barrier function was assessed by measurement of trans epidermal water loss (TEWL) and stratum corneum hydration (SCH) in belly and pinna of the dogs on days 0, 15, 30, and 45 of each period. A trend for higher antioxidant effect significant reduction in serum scavenging capacity was found with PBP for BSFL diet trough malondialdehyde and Vitamin E measurement in dog's serum 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. When fed PBP diet dogs exhibited reduction in serum cholesterol triglycerides and decreased LDL levels after 50 days, while dogs fed BSFL presented significant reduction in ALT. TEWL was significantly reduced in belly and pinna over time when dogs were fed BSFL, and TEWL in belly was significantly lower in dogs fed BSFL in comparison to PBP. while Increased SCH was also higher for the BSFL group observed in the same along the feeding period in comparison to PBP, indicating improved ability of the dogs to retain water and keep skin moisture. Improvement skin barrier function could be related to fatty acids from BSFL and increased sebaceous lipids in skin. These are responsible for to avoid water loss and improve skin protection against microbial insults. Inclusion of BSFL as protein source did not promote negative changes in blood biochemistry and had minor antioxidant effect in healthy dogs. However, it proved effective in improving skin barrier function, making BSFL a valuable alternative protein source for dogs, particularly those with sensitive skin or allergies manifesting on the skin.


Subject(s)
Animal Feed , Antioxidants , Cross-Over Studies , Diet , Larva , Animals , Dogs/physiology , Animal Feed/analysis , Antioxidants/metabolism , Diet/veterinary , Larva/physiology , Larva/chemistry , Male , Female , Animal Nutritional Physiological Phenomena , Simuliidae/physiology , Simuliidae/chemistry , Skin/chemistry , Skin/metabolism , Skin Physiological Phenomena
13.
Free Radic Res ; 58(6-7): 367-379, 2024.
Article in English | MEDLINE | ID: mdl-38962912

ABSTRACT

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.


I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.


Subject(s)
Indoles , Inflammation , Nanocapsules , Oxidative Stress , Skin , Wound Healing , Animals , Indoles/pharmacology , Rats , Wound Healing/drug effects , Oxidative Stress/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Skin/drug effects , Skin/pathology , Skin/metabolism , Nanocapsules/chemistry , Male , Rats, Wistar , Antioxidants/pharmacology
14.
Photodermatol Photoimmunol Photomed ; 40(4): e12985, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38845468

ABSTRACT

BACKGROUND: Photoprotection is the first measure in the prevention and treatment of the deleterious effects that sunlight can cause on the skin. It is well known that prolonged exposure to solar radiation leads to acute and chronic complications, such as erythema, accelerated skin aging, proinflammatory and procarcinogenic effects, and eye damage, among others. METHODS: A better understanding of the molecules that can protect against ultraviolet radiation and their effects will lead to improvements in skin health. RESULTS: Most of these effects of the sunlight are modulated by oxidative stress and proinflammatory mechanisms, therefore, the supplementation of substances that can regulate and neutralize reactive oxygen species would be beneficial for skin protection. Current evidence indicates that systemic photoprotection should be used as an adjunctive measure to topical photoprotection. CONCLUSION: Oral photoprotectors are a promising option in improving protection against damage induced by UVR, as they contain active ingredients that increase the antioxidant effects of the body, complementing other photoprotection measures. We present a review of oral photoprotectors and their effects.


Subject(s)
Protective Agents , Ultraviolet Rays , Humans , Administration, Oral , Antioxidants/administration & dosage , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Skin/metabolism , Skin/radiation effects , Skin/drug effects , Sunlight/adverse effects , Ultraviolet Rays/adverse effects , Protective Agents/administration & dosage
15.
Toxicol In Vitro ; 99: 105883, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38936442

ABSTRACT

Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines. Reconstructed skin with melanoma were development using human fibroblasts (MRC5), human epidermal keratinocytes (HaCat), and human melanoma (SK-MEL-28) embedded in collagen type I. The structure was characterized by hematoxylin-eosin stained, as well as points of melanoma cell invasion, which was associated with activity of MMPs (MMP-2 and MMP-9) by zymographic method. Then, the gene expression of the target molecular mechanisms involved in melanoma progression were evaluated. Here, the model development showed a region epidermis organized and separated from the dermis, with fibroblast cells confined and melanoma cells form delimited area invasion. MMP-2 and MMP-9 were identified during of cell culture and gene expression of BRAF, NRAS, and Vimentin was confirmed. The proposed model provides one more opportunity to study in vitro tumor biology of melanoma and also to allows the study of new drugs with more reliable results then whats we would find in vivo.


Subject(s)
Fibroblasts , Matrix Metalloproteinase 2 , Matrix Metalloproteinase 9 , Melanoma , Skin Neoplasms , Humans , Melanoma/pathology , Melanoma/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Skin Neoplasms/pathology , Fibroblasts/metabolism , Fibroblasts/drug effects , Cell Line, Tumor , Skin/metabolism , Skin/pathology , Neoplasm Invasiveness , Keratinocytes/drug effects , Cell Line , Vimentin/metabolism , Vimentin/genetics
16.
Nanotechnology ; 35(40)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38901412

ABSTRACT

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.


Subject(s)
Drug Carriers , Humans , Drug Carriers/chemistry , Nanoparticles/chemistry , Hyperpigmentation/drug therapy , Skin Lightening Preparations/administration & dosage , Skin Lightening Preparations/chemistry , Skin/drug effects , Skin/metabolism
17.
Int J Pharm ; 660: 124319, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38866084

ABSTRACT

Tissue-engineered products (TEPs) are at the forefront of developmental medicines, precisely where monoclonal antibodies and recombinant cytokines were 30 years ago. TEPs development for treating skin wounds has become a fast-growing field as it offers the potential to find novel therapeutic approaches for treating pathologies that currently have limited or no effective alternatives. This review aims to provide the reader with the process of translating an idea from the laboratory bench to clinical practice, specifically in the context of TEPs designing for skin wound healing. It encompasses historical perspectives, approved therapies, and offers a distinctive insight into the regulatory framework in Brazil. We explore the essential guidelines for quality testing, and nonclinical proof-of-concept considering the Brazilian Network of Experts in Advanced Therapies (RENETA) and International Standards and Guidelines (ICH e ISO). Adopting a multifaceted approach, our discussion incorporates scientific and industrial perspectives, addressing quality, biosafety, non-clinical viability, clinical trial and real-word data for pharmacovigilance demands. This comprehensive analysis presents a panoramic view of the development of skin TEPs, offering insights into the evolving landscape of this dynamic and promising field.


Subject(s)
Skin , Tissue Engineering , Wound Healing , Humans , Wound Healing/drug effects , Tissue Engineering/methods , Animals , Skin/drug effects , Skin/metabolism , Skin/injuries , Brazil
18.
J Transl Med ; 22(1): 424, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704581

ABSTRACT

BACKGROUND: The measurement of the skin carotenoids using the Veggie Meter® has emerged as a rapid objective method for assessing fruit and vegetable intake, highly recommended by the Mediterranean Diet (MD), which represents one of the healthiest dietary patterns, worldwide. This study aimed to examine differences in skin carotenoid content and degree of adherence to the MD pattern between two adult populations from Southern Italy and the Dominican Republic. METHODS: This cross-sectional study enrolled a total of 995 adults, 601 subjects from Italy and 394 from the Dominican Republic. All participants underwent anthropometric measurements and skin carotenoid assessment by Veggie Meter®. Adherence to the MD and lifestyle were evaluated using the Mediterranean Diet Adherence Screener (MEDAS) and the Mediterranean Lifestyle Index (MEDLIFE) questionnaires. Correlations between the skin carotenoid and MEDAS score were estimated using Pearson's correlation coefficient. Multiple linear regression models were created to determine variables that affect skin carotenoid score for both populations. RESULTS: Mean total skin carotenoids were higher in the Italian compared to the Dominican Republic population (342.4 ± 92.4 vs 282.9 ± 90.3; p < 0.005) regardless of sex (women: 318.5 ± 88.9 vs 277.3 ± 91.9, p < 0.005 and men: 371.7 ± 88.3 vs 289.5 ± 88.1, p < 0.005), and remaining statistically significant after age-adjustment of the Dominican Republic sample. Using the MEDAS questionnaire, we found a higher MD adherence score in the Italian than in the Dominican Republic population also after age-adjusting data (7.8 ± 2.1 vs 6.2 ± 3.7; p < 0.005) and even when categorized by sex (Italian vs age-adjusted Dominican Republic women: 7.9 ± 2.1 vs 6.3 ± 2.6; Italian vs age-adjusted Dominican Republic men: 7.7 ± 2.2 vs 6.0 ± 4.7; p < 0.005). Using the MEDLIFE test, total Italians presented a lower score with respect to the age-adjusted Dominican Republic population (3.2 ± 1.2 vs 3.4 ± 1.4; p < 0.05). In multiple regression analysis, skin carotenoids were associated with sex and negatively associated with BMI in the Italian population (sex: ß: 54.95; 95% CI: 40.11, 69.78; p < 0.0001; BMI: ß: - 1.60; 95% CI: - 2.98,0.86; p = 0.03), while they resulted associated with age and sex in the Dominican Republic population (age: ß: 2.76; 95% CI: 1.92, 3.56; p < 0.001; sex: ß: 23.29; 95% CI: 5.93, 40.64; p = 0.009). Interestingly, skin carotenoids were positively correlated with MEDAS score in both populations (Italy: r = 0.03, p < 0.0001, Dominican Republic: r = 0.16, p = 0.002). CONCLUSIONS: This study provides the assessment of the adherence to the MD and skin carotenoid content in adults living in Southern Italy and the Dominican Republic, showing a higher MD adherence score and a skin carotenoid content in inhabitants from the Mediterranean region. Our findings highlight the need to globally encourage fruit and vegetable intake, particularly in non-Mediterranean area.


Subject(s)
Carotenoids , Diet, Mediterranean , Skin , Humans , Italy , Dominican Republic , Carotenoids/analysis , Carotenoids/metabolism , Female , Male , Adult , Skin/metabolism , Middle Aged , Cross-Sectional Studies , Patient Compliance/statistics & numerical data , Surveys and Questionnaires
19.
Sci Rep ; 14(1): 10193, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702361

ABSTRACT

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.


Subject(s)
Amphibians , Arsenic , Microbiota , Skin , Animals , Arsenic/metabolism , Arsenic/toxicity , Microbiota/drug effects , Skin/microbiology , Skin/drug effects , Skin/metabolism , Amphibians/microbiology , Bacteria/drug effects , Bacteria/classification , Bacteria/metabolism , Bacteria/genetics , Permeability/drug effects
20.
Sci Data ; 11(1): 441, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702328

ABSTRACT

Photoaging is the premature aging of the skin caused by prolonged exposure to solar radiation. The visual alterations manifest as wrinkles, reduced skin elasticity, uneven skin tone, as well as other signs that surpass the expected outcomes of natural aging. Beyond these surface changes, there is a complex interplay of molecular alterations, encompassing shifts in cellular function, DNA damage, and protein composition disruptions. This data descriptor introduces a unique dataset derived from ten individuals, each with a minimum of 18 years of professional experience as a driver, who are asymmetrically and chronically exposed to solar radiation due to their driving orientation. Skin samples were independently collected from each side of the face using a microdermabrasion-like procedure and analyzed on an Exploris 240 mass spectrometer. Our adapted proteomic statistical framework leverages the sample pairing to provide robust insights. This dataset delves into the molecular differences in exposed skin and serves as a foundational resource for interdisciplinary research in photodermatology, targeted skincare treatments, and computational modelling of skin health.


Subject(s)
Face , Mass Spectrometry , Proteomics , Skin Aging , Skin , Skin/radiation effects , Skin/metabolism , Humans , Sunlight
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