RESUMO
Wound healing is a complex process involving molecular and structural interactions. Transforming growth factor ß (TGF-ß), the renin-angiotensin system (RAS), and other important mediators play a central role on wound healing process. This study examined the dynamics of healing in healthy, hypertensive, and diabetic rats treated with or without Losartan, focusing on healing rate, scar characteristics, and molecular modulation. Macroscopic and microscopic analyses revealed delayed healing and reduced collagen deposition in diabetic and hypertensive rats compared with normoglycemic controls. Losartan affected healing by regulating TGF-ß expression and collagen organization. In the groups of hypertensive and diabetic rats treated with losartan, healing aesthetics improved by less collagen deposition and consequently minor chances to fibrosis development, probably due to lower TGFß and SMADs expression. Diabetic rats showed reduced skin and collagen fiber thickness, whereas hypertensive rats showed better healing under Losartan treatment (LT). These results demonstrate the complex interactions between LT, diabetes and hypertension on important fibrotic and inflammatory pathways. Although LT successfully reduces TGF-ß expression and classical SMAD signaling in hypertensive settings, its minor effect in diabetes conditions indicate the necessity of supplemental treatments that target mechanisms unique to hyperglycemia, such as glycation end products or oxidative stress inhibitors. To improve treatment outcomes for individuals with diabetes and hypertension comorbidities, future studies should investigate the combination of multi-pathway modulators.
Assuntos
Diabetes Mellitus Experimental , Hipertensão , Losartan , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Losartan/farmacologia , Losartan/uso terapêutico , Ratos , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Fator de Crescimento Transformador beta/metabolismo , Colágeno/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Ratos Wistar , Pele/patologia , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
Skin diseases may cause rash, inflammation, itchiness, and other important skin changes, including dysplasia. Some skin conditions may be due to genetic and lifestyle factors and immune-mediated factors. The current skin disease treatment can include oral medication, topical cream, or ointments. Nanotechnology is revolutionizing the drug delivery systems, increasing the time life of active therapeutic compounds and improving the treatment efficiency. This work hypothesizes that varying the surface properties of chitosan nanoparticles (Ch-NPs) can modulate their diffusion through dermal tissue. Thus, Ch-NPs were synthesized, and their surface was modified with polyethylene glycol, oxalic acid, and linoleic acid for transdermal therapy. The different Ch-NPs were labeled with a fluorophore, and the dermal diffusion was measured on human skin by histological preparations and fluorescent microscopy. The surface properties of nanoparticles were shown to play an essential role in skin diffusion rate. Surface modification with a lipophilic moiety such as linoleic fatty acid showed a diffusion rate of 7.23 mm2/h in human full-thickness abdominal flap, which is 2.7 times faster nanoparticle diffusion through dermal tissue when compared with the unmodified Ch-NPs (2.92 mm2/h). The positive (zeta potential +27.5 mV) or negative (zeta potential -2.2 mV) surface charge does not affect the chitosan nanoparticle diffusion. Polyethylene glycol surface modification slightly improved the nanoparticle diffusion rate (3.63 mm2/h). Thus, modulating the nanoparticle surface properties can control the skin diffusion rate. The implications of this finding on dermic drug delivery are discussed.
Assuntos
Quitosana , Nanopartículas , Pele , Propriedades de Superfície , Quitosana/química , Nanopartículas/química , Humanos , Pele/metabolismo , Pele/efeitos dos fármacos , Difusão , Polietilenoglicóis/química , Absorção Cutânea , Sistemas de Liberação de Medicamentos/métodos , Administração Cutânea , Ácido Linoleico/químicaRESUMO
Background/Objectives: Vitamin D (VD) plays a crucial role in age-related diseases, and its influence on cellular senescence (CS) could help clarify its function in aging. Considering VD's pleiotropic effects and the heterogeneity of CS. Methods: we utilized single-cell RNA sequencing (scRNA-seq) to explore these dynamics across multiple tissues. We analyzed three murine tissue datasets (bone, prostate, and skin) obtained from public repositories, enriching for senescence gene signatures. We then inferred gene regulatory networks (GRNs) at the tissue and cell-type levels and performed two cell communication analyses: one for senescent cells and another for interactions between senescent and non-senescent cells. Results: VD supplementation significantly decreased senescence scores in the skin (p = 3.96×10-134) and prostate (p=1.56×10-34). GRN analysis of the prostate revealed an altered macrophage-fibroblast regulatory relationship. In bone, distinct aging-related modules emerged for different bone lineages. In skin, contrary differentiation patterns between suprabasal and basal cells were observed. The main VD-modulated pathways were involved in inflammation, extracellular matrix remodeling, protein metabolism, and translation. VD reduced fibroblast-macrophage interactions in the prostate and skin but increased overall cellular crosstalk in bone. Conclusions: Our findings demonstrate that VD alleviates CS burden across tissues by modulating inflammation and metabolic processes and promoting differentiation. Key aging-related genes modulated by VD were linked to anabolism and cellular differentiation, suggesting VD's potential for therapeutic interventions targeting age-related diseases.
Assuntos
Senescência Celular , Análise de Célula Única , Pele , Vitamina D , Animais , Camundongos , Vitamina D/farmacologia , Masculino , Senescência Celular/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Próstata/metabolismo , Próstata/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Envelhecimento/genética , Transcriptoma/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismoRESUMO
In vitro release testing (IVRT) serves as a crucial tool to assess the quality, physicochemical behavior, and performance of semisolid formulations already available on the market. In vitro skin permeation studies (IVPT) are widely used to evaluate the safety and efficacy profiles of topical drugs, utilizing biological membranes prepared from ex vivo human and porcine skin tissues. This study aimed to develop and validate a discriminative IVRT method to evaluate various marketed topical benzoyl peroxide formulations. Additionally, IVPT was employed to assess skin permeation and retention profiles of these formulations, comparing porcine skin results with those obtained by using ex vivo human skin tissues. Physicochemical differences among the evaluated benzoyl peroxide formulations were identified, with the poloxamer-based formulation exhibiting a higher release rate. IVPT using both porcine and human skin differentiated retention and skin permeation profiles, with the poloxamer-based formulation demonstrating greater skin retention capacity compared to the other formulations evaluated. Similar conclusions on benzoyl peroxide retention and cutaneous permeation were drawn from both porcine and human skin IVPT tests, confirming the correlation between the two models.
Assuntos
Administração Cutânea , Peróxido de Benzoíla , Absorção Cutânea , Pele , Humanos , Suínos , Peróxido de Benzoíla/farmacocinética , Peróxido de Benzoíla/química , Peróxido de Benzoíla/administração & dosagem , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Animais , Permeabilidade , Liberação Controlada de Fármacos , Poloxâmero/química , Técnicas In Vitro , Química Farmacêutica/métodosRESUMO
INTRODUCTION: Collagen is essential to skin structure and integrity, and it is continually degraded with aging due to higher oxidative stress. Sleep deprivation accelerates skin aging and reduces collagen production. Good sleep may be a potential adjuvant to the efficacy of oral supplementation with collagenic peptides for the skin. OBJECTIVES: To summarize clinical benefits to the skin of collagen intake, and consider the role of sleep in its effectiveness. METHODS: Studies in the PubMed database that reported the effects of oral administration of collagen peptides were searched; and studies presenting the association of collagen metabolism with sleep. RESULTS: A total of 1117 articles were initially identified; 66 were reviewed in full. Most involved women at third or fourth decade of life. Daily collagen doses ranged from 1 to 10 g, with intervention periods lasting from 4 to 8 weeks. Consistent improvements in skin elasticity, hydration, and wrinkle reduction were observed, with increase in dermal density and structural proteins. Collagen combined with vitamins, minerals, and antioxidants provided additional benefits, including improved skin radiance and reduced pore size. Studies on sleep and skin indicated that poor sleep can impair skin hydration, increase transepidermic water loss, and reduce elasticity, highlighting the potential role of sleep in maximizing the benefits of collagen supplementation. CONCLUSIONS: Hydrolyzed collagen supplementation, particularly at 2.5 g/day, has shown benefits for skin after 4 weeks of use. Sleep quality may enhance these effects by supporting immune function and reducing oxidative stress. Further studies are needed on sleep's role in enhancing collagen supplementation benefits.
Assuntos
Colágeno , Suplementos Nutricionais , Envelhecimento da Pele , Pele , Envelhecimento da Pele/efeitos dos fármacos , Humanos , Colágeno/metabolismo , Colágeno/administração & dosagem , Administração Oral , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Qualidade do Sono , Feminino , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/administração & dosagemRESUMO
UVA radiation and visible light can lead to indirect damage to DNA, proteins, and lipids through photosensitized reactions, where a molecule undergoes a photochemical alteration by the initial absorption of radiation by another molecular entity called photosensitizer (Sens). The chemical changes undergone by biomolecules in photosensitized reactions can trigger important adverse processes such as photoallergy, phototoxicity, and skin cancer, among others. Despite the knowledge about photosensitized reactions and the fact that many endogenous compounds present in the skin can act as Sens, UVA, and visible light are widely used in several devices for domestic and general use without a thorough evaluation of their possible harmful effects; one prominent example is UV-nail polish dryers. The information in the literature about the possible damage that can be caused by using this type of radiation source is controversial. In this work, we demonstrate that the radiation dose emitted by the nail polish dryer device during a typical gel nail manicure session effectively degrades molecules present in the skin under physiological and pathological conditions. Additionally, it may induce damage to biomolecules such as proteins and lipids due to the photosensitization process, leading to the loss of their biological functions.
Assuntos
Pele , Raios Ultravioleta , Humanos , Pele/efeitos dos fármacos , Pele/metabolismo , Raios Ultravioleta/efeitos adversos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Unhas/química , Unhas/efeitos da radiação , Unhas/efeitos dos fármacos , Proteínas/química , Proteínas/metabolismo , Dermatite Fototóxica/etiologia , Luz/efeitos adversos , DNA/químicaRESUMO
The search for innovative materials for manufacturing skin dressings is constant and high demand. In this context, the present study investigated the effects of a 3D printed skin dressing made of spongin-like collagen (SC) extract from marine sponge (Chondrilla caribensis), used in 3 concentrations of SC and alginate (C1, C2, C3). For this proposal, the physicochemical, morphological andin vitrobiological results were investigated. The results demonstrated that, after immersion, C2 presented a higher mass loss and C3 present a higher pH in experimental periods. Also, a higher porosity was observed for C1 and C2 skin dressings, with a higher swelling ratio for C2. For Fourier transform infrared, peaks of Amide A, -CH2, -COOH and C-O-C were seen. Moreover, the macroscopic image demonstrated a skin dressing with rough surface and grayish color that is naturally observed inChondrilla caribensis. For scanning electron microscopy analysis the presence of pores could be observed for all skin dressings, with fibers disposed in layers. Thein vitroanalyses demonstrated the viability of HFF-1 and L929 cell lines 70% of the values found for cell proliferation compared to Control Group. Furthermore, the cell adhesion analysis demonstrated that both cell lines adhered to the 3 different skin dressings and non-cytotoxicity was observed. Taking together, all the results suggest that the skin dressings are biocompatible and present non-cytotoxicity in thein vitrostudies, being considered a suitable material for tissue engineering proposals.
Assuntos
Materiais Biocompatíveis , Colágeno , Teste de Materiais , Poríferos , Impressão Tridimensional , Animais , Colágeno/química , Poríferos/química , Camundongos , Porosidade , Humanos , Linhagem Celular , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Alginatos/química , Bandagens , Sobrevivência Celular/efeitos dos fármacos , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Fibroblastos/citologia , Microscopia Eletrônica de Varredura , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Pele ArtificialRESUMO
Drug delivery through the skin is a widely used therapeutic method for the treatment of local dermatologic conditions. Dermal and transdermal methods of drug delivery offer numerous advantages, but some of the most important aspects of drug absorption through the skin need to be considered. Film-forming systems (FFS) represent a new mode of sustained drug delivery that can be used to replace traditional topical formulations such as creams, ointments, pastes, or patches. They are available in various forms, including solutions, gels, and emulsions, and can be categorised as film-forming gels and film-forming emulsions. Film-forming emulsions (FFE) are designed as oil-in-water (O/W) emulsions that form a film with oil droplets encapsulated in a dry polymer matrix, thus maintaining their dispersed nature. They offer several advantages, including improved solubility, bioavailability and chemical stability of lipophilic drugs. In addition, they could improve the penetration and diffusion of drugs through the skin and enhance their absorption at the target site due to the nature of the components used in the formulation. The aim of this review is to provide an up-to-date compilation of the technologies used in film-forming emulsions to support their development and availability on the market as well as the development of new pharmaceutical forms.
Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Emulsões , Absorção Cutânea , Pele , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Absorção Cutânea/fisiologia , Humanos , Pele/metabolismo , Química Farmacêutica/métodos , Solubilidade , Preparações Farmacêuticas/química , Preparações Farmacêuticas/administração & dosagem , Animais , Polímeros/químicaRESUMO
This study sought to examine the effects of systemic ozone (O3) treatment on the healing of skin wounds induced on the dorsal surface of Wistar rats. The skin wounds were created using a 10 mm round punch following the sagittal medial plane in 72 rats. Then, the animals were randomly assigned to four groups, each receiving the following treatments: group C, which did not undergo treatment with the O3/O2 mixture; group OZ0.3, administered the O3/O2 mixture at a dose of 0.3 mg/kg; group OZ0.7, given the O3/O2 mixture at a dose of 0.7 mg/kg; and group OZ1.0, provided with the O3/O2 mixture at a dose of 1.0 mg/kg. Six animals from each group were euthanized at 7, 14, and 21 days postoperatively. Clinical, histological, histometric, and immunohistochemical (IHC) analyses were accomplished. Data from clinical and histometric assessments revealed that OZ0.7 and OZ1.0 demonstrated more favorable healing, with greater wound contraction observed in the OZ1.0 group at 14 and 21 days. Histologically, the OZ1.0 group exhibited aspects consistent with an accelerated tissue repair process. IHC analysis revealed greater vascular endothelial growth factor (VEGF) immunostaining in the OZ0.7 (7 days) and OZ1.0 (7 and 14 days) groups compared to the C group. Expression of transforming growth factor beta-1 was significantly increased in the OZ0.7 (14 days) and OZ1.0 (7 and 14 days) groups compared to the C group. In conclusion, our data suggest that systemic use of O3 enhanced tissue repair in cutaneous wounds in a dose-dependent manner, with concentrations of 1.0 mg/kg providing the most beneficial effects. Furthermore, the results of this study implicate the use of O3 for the treatment of skin wounds aiming at improving the healing process over time. Our findings suggest the use of O3 as a viable alternative to enhance wound healing and repair.
Assuntos
Ozônio , Ratos Wistar , Pele , Cicatrização , Animais , Ozônio/farmacologia , Cicatrização/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Pele/metabolismo , Pele/patologia , Ratos , Masculino , Imuno-Histoquímica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
3D skin models have been explored as an alternative method to the use of animals in research and development. Usually, human skin equivalents comprise only epidermis or epidermis/dermis layers. Herein, we leverage 3D bioprinting technology to fabricate a full-thickness human skin equivalent with hypodermis (HSEH). The collagen hydrogel-based structure provides a mimetic environment for skin cells to adhere, proliferate and differentiate. The effective incorporation of the hypodermis layer is evidenced by scanning electron microscopy, immunofluorescence, and hematoxylin and eosin staining. The transcriptome results underscore the pivotal role of the hypodermis in orchestrating the genetic expression of a multitude of genes vital for skin functionality, including hydration, development and differentiation. Accordingly, we evidence the paramount significance of full-thickness human skin equivalents with hypodermis layer to provide an accurate in vitro platform for disease modeling and toxicology studies.
Assuntos
Bioimpressão , Impressão Tridimensional , Pele , Humanos , Bioimpressão/métodos , Pele/metabolismo , Engenharia Tecidual/métodos , Hidrogéis , Alicerces Teciduais , Queratinócitos/metabolismo , Regulação da Expressão Gênica , Pele Artificial , Diferenciação CelularRESUMO
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 â¼80 % 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.
Assuntos
Administração Cutânea , Dexametasona , Sulfeto de Hidrogênio , Pele , Sulfeto de Hidrogênio/administração & dosagem , Sulfeto de Hidrogênio/química , Dexametasona/administração & dosagem , Dexametasona/química , Animais , Pele/metabolismo , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Psoríase/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/químicaRESUMO
The integumentary system serves as a crucial protective barrier and is subject to complex signaling pathways that regulate its physiological functions. As the body's first line of defense, the skin is continuously exposed to environmental stressors, necessitating a robust network of signaling molecules to maintain homeostasis. Considering the main cellular components to be keratinocytes, melanocytes, fibroblasts, and fibrous components, collagen of various types, this review explores the intricate signaling mechanisms that govern skin integrity, focusing on key pathways involved in impacts of ageing and environment factors on skin health. The role of growth factors, cytokines, hormones and other molecular mediators in these processes is examined. Specially for women, decrease of estrogen is determinant to alter signaling and to compromise skin structure, especially the dermis. Environmental factors, such as ultraviolet rays and pollution alongside the impact of ageing on signaling pathways, especially TGF-ß and proteases (metalloproteinases and cathepsins). Furthermore, with advancing age, the skin's capacity to shelter microbiome challenges diminishes, leading to alterations in signal transduction and subsequent functional decline. Understanding these age-related changes is essential for developing targeted therapies aimed at enhancing skin health and resilience, but also offers a promising avenue for the treatment of skin disorders and the promotion of healthy ageing.
Assuntos
Envelhecimento , Comunicação Celular , Transdução de Sinais , Pele , Humanos , Pele/metabolismo , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Comunicação Celular/fisiologia , Envelhecimento da Pele/fisiologia , AnimaisRESUMO
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.
Assuntos
Quitosana , Ácido Hialurônico , Membranas Artificiais , Pele , Cicatrização , Quitosana/química , Quitosana/farmacologia , Animais , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Cicatrização/efeitos dos fármacos , Ratos , Pele/lesões , Pele/metabolismo , Masculino , Ratos Wistar , BandagensRESUMO
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.
Assuntos
Sulfatos de Condroitina , Nanopartículas , Sulfatos de Condroitina/química , Animais , Suínos , Nanopartículas/química , Regeneração/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Administração Tópica , Nanoestruturas/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
Obesity is a complex multifactorial disease in which excess body fat triggers negative health effects. Systemically, obesity causes several changes, such as inflammation, oxidative stress, mitochondrial dysfunction and apoptosis; factors linked to the slow and incomplete epithelial regenerative process. Specifically, in the integumentary system, obesity causes an expansion of the skin's surface area and changes in collagen deposition. Molecular underpinnings of why obesity delays wound healing are still poorly understood. In addition to the primary role of dermal adipocytes in lipid storage and heat insulation, they also promote skin immunity, wound healing and hair follicle cycling. As a consequence of the cellular and dysfunctional adaptations of adipocytes, inflammatory immune alterations, alteration in the expression of proteins genes associated with the blood supply, altered collagen formation through fibroblast senescence and excessive degradation of extracellular matrix proteins are metabolic characteristics of the system in obesity that contribute to sustained inflammation and decreased mechanical resistance of the skin.
Assuntos
Obesidade , Pele , Cicatrização , Humanos , Obesidade/metabolismo , Cicatrização/fisiologia , Pele/metabolismo , Adipócitos/metabolismo , Inflamação/metabolismo , Estresse OxidativoRESUMO
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.
Assuntos
Apoptose , Autofagia , Fibroblastos , Glucosilceramidase , Mitocôndrias , Estresse Oxidativo , Glucosilceramidase/metabolismo , Glucosilceramidase/genética , Humanos , Fibroblastos/metabolismo , Autofagia/genética , Mitocôndrias/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/patologia , Pele/metabolismo , Pele/patologia , Lisossomos/metabolismo , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , MutaçãoRESUMO
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.
Assuntos
Administração Cutânea , Dacarbazina , Iontoforese , Melanoma , Absorção Cutânea , Neoplasias Cutâneas , Iontoforese/métodos , Melanoma/tratamento farmacológico , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Linhagem Celular Tumoral , Dacarbazina/administração & dosagem , Dacarbazina/farmacocinética , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Pele/metabolismo , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Sistemas de Liberação de MedicamentosRESUMO
The imbalance in oxidant production and chronic inflammation are the main mechanisms that lead to the detrimental effects of diabetes on skin wound healing. Thus, administration of antioxidants could improve diabetic wound healing. This study aimed to understand the effects of extra virgin olive oil (EVOO) or hydroxytyrosol (HT) in skin wound healing under diabetic conditions. Skin wounds in streptozotocin-induced diabetic mice were topically treated with HT. Some diabetic animals were fed with a diet rich in EVOO. Wounds were harvested 7 days later. In in vitro assays, fibroblasts and macrophages were treated with high levels of glucose and HT. The EVOO or HT promoted wound closure and collagen deposition in diabetic mouse wounds. The EVOO or HT reduced the number of infiltrated neutrophils, tumour necrosis factor-α, lipid peroxidation, and nuclear factor erythroid 2-related factor 2 in diabetic mouse wounds. The EVOO or HT also increased the number of macrophages with anti-inflammatory phenotype and interleukin-10 in diabetic mouse wounds. In the in vitro assays, HT promoted the fibroblast migration, collagen gel contraction, and switched macrophages to an anti-inflammatory phenotype under high glucose conditions. In conclusion, the diet supplementation with EVOO or topical application of HT promotes skin wound healing under diabetic conditions and can be a possible therapeutic tool for the treatment of those lesions.
Assuntos
Diabetes Mellitus Experimental , Azeite de Oliva , Álcool Feniletílico , Cicatrização , Animais , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Cicatrização/efeitos dos fármacos , Azeite de Oliva/farmacologia , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Antioxidantes/farmacologia , Pele/lesões , Pele/patologia , Pele/efeitos dos fármacos , Pele/metabolismo , Masculino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Polifenóis/farmacologiaRESUMO
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.
Assuntos
Lasers Semicondutores , Ratos Wistar , Pele , Animais , Masculino , Ratos , Lasers Semicondutores/uso terapêutico , Pele/efeitos da radiação , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Rejuvenescimento , Modelos AnimaisRESUMO
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.