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1.
Life Sci ; 252: 117667, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32304761

RESUMO

AIMS: Pantothenic acid (PA) has been applied to treat alopecia, but the underlying mechanism is still unclear. Our study aims to explore the underlying mechanism of PA in regulating hair follicle (HF) growth. MAIN METHODS: Mink HFs and dermal papilla (DP) cells were isolated and cultured in vitro. HFs and DP cells were treated with 0, 10, 20, 40 µg/ml PA. The effect of PA on HF growth, DP cell proliferation, cell cycle distribution, cell migration, and insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expressions in DP cells was measured. Moreover, the effect of PA on inhibitor of DNA binding 3 (ID3)/Notch signaling pathway was analyzed. Subsequently, ID3 was silenced to validate whether ID3/Notch signaling pathway was involved in regulating DP cell proliferation by PA. KEY FINDINGS: Both 20 µg/ml and 40 µg/ml PA promoted HF growth, G1/S transition of DP cells and IGF-1 and VEGF expressions in DP cells, while only 20 µg/ml PA promoted cell viability and the migration of DP cells. Thus 20 µg/ml PA was chosen for the following experiments. PA treatment was found to up-regulate ID3 expression but down-regulate Notch receptor 1 (Notch1) and Notch signaling targets expressions. Furthermore, ID3 knockdown reversed PA-induced cell proliferation and inhibition of Notch1 and Notch signaling targets expressions, indicating that PA-induced DP cell proliferation and inhibition of Notch signaling were mediated via up-regulation of ID3. SIGNIFICANCE: This study provides an underlying mechanism related to the effect of PA on stimulating DP cell proliferation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Derme/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Ácido Pantotênico/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Derme/citologia , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Folículo Piloso/citologia , Proteínas Inibidoras de Diferenciação/metabolismo , Masculino , Vison , Ácido Pantotênico/administração & dosagem , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Tissue Cell ; 63: 101323, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223958

RESUMO

Previous reports showed that fibronectin (FN) was effective in stimulating the recovery of damaged dermis. However, native FN has multifunctional domains transmitting beneficial as well as unbeneficial signals to dermal tissue cells through the mediation of integrin heterodimers. The use of a functional domain [FN type III9-10 fragments (FNIII9-10)] providing beneficial effects on the physiology of dermal tissue cells would enhance an in vitro culture system for dermal fibroblasts (DFs). We therefore investigated the FNIII9-10-derived extracellular signaling effect on the physiology of DFs during in vitro culture. Recombinant FNIII9-10 proteins were constructed and their functionality was determined by observing the adhesion of adult human DFs (aHDFs) to recombinant FNIII9-10 and of low adhesion integrin α5ß1- and αvß3-blocked aHDFs to recombinant FNIII9-10. Cellular proliferation, morphology, and senescence were measured and compared in the aHDFs cultured on native FN and recombinant FNIII9-10 for short or long periods. The results show that recombinant FNIII9-10-derived extracellular signaling stimulated increased proliferation of aHDF (both in short- and long-term cultures) and inhibited the generation of morphological abnormalities (in short- and long-term cultures) and cellular senescence (long-term culture) when compared with native FN-derived extracellular signaling. Our results suggest that, instead of native FN, recombinant FNIII9-10 better enhanced the in vitro culture of aHDFs while diminishing the adverse effects associated with the use of human-derived materials.


Assuntos
Senescência Celular/genética , Derme/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibronectinas/genética , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Proliferação de Células/genética , Células Cultivadas , Derme/metabolismo , Fibroblastos/metabolismo , Domínio de Fibronectina Tipo III/genética , Fibronectinas/farmacologia , Humanos , Integrina alfa5beta1/genética , Transdução de Sinais/genética
4.
J Cosmet Dermatol ; 19(1): 226-233, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31904184

RESUMO

BACKGROUND: The dermis, composed predominantly of dermal fibroblasts and extracellular matrix (ECM), consists of fibrous proteins such as collagen and elastin and is associated with wrinkle formation and dermal elasticity. As the major constituent of the dermal matrix, collagen strengthens the skin, enhances its elasticity and protects it from external factors, such as ultraviolet (UV) rays, skin inflammation, intracellular metabolites, and aging. AIMS: Economic growth and long-life expectancy have increased the interest in beauty, with extensive studies conducted to evaluate the anti-aging and health-promoting benefits of bioactive substances. METHODS: In this study, we used natural ingredients, Trapa japonica fruit is a hard, aquatic plant that grows in ponds or marshes and contains protein and starch. To develop the ingredients for comprehensive skin improvement, this study investigated the effects of the trapa japonica fruit extract on the improvement of skin cells. CONCLUSION: We investigated the role of the fermented hot-water trapa japonica fruit extract to isolate the active ingredients with antiwrinkle effects in vitro and ex vivo situation through human dermal fibroblast cell proliferation via activating TGF-ß1/GSK-3ß/ß-catenin pathway.


Assuntos
Colágeno/biossíntese , Derme/efeitos dos fármacos , Lythraceae/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Derme/metabolismo , Elasticidade/efeitos dos fármacos , Fermentação , Fibroblastos , Frutas/química , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Envelhecimento da Pele/efeitos dos fármacos , Solventes/química , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo
5.
Lasers Med Sci ; 35(6): 1341-1347, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31900691

RESUMO

Staphylococcus aureus is one of the main causative agent of infections acquired in both community and hospital environment. In this context, photodynamic therapy (PDT) consists in using a photosensitizer that, activated by light, evokes the formation of reactive oxygen species (ROS), which lead to the death of microorganisms due to oxidative damage; it is useful tool since this action, harmful to pathogens, does not significantly injure human cells. In view of this, this work proposes a more in-depth study on the use of resveratrol (RSV) as a possible photosensitizer. It was observed, in the intradermal infection model in animals' ear dermis, that photoactivated resveratrol promotes an increase in myeloperoxidase expression with reduced bacterial load in the draining lymph node. Besides that, the draining lymph node of the animals treated with photoactivated RSV controls inflammation through IL-10 production. These are pioneers data and this work being a pilot study; then, other works must be conducted with the objective of elucidate the photoactivated resveratrol mechanism of action.


Assuntos
Luz , Resveratrol/efeitos da radiação , Resveratrol/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Carga Bacteriana/efeitos dos fármacos , Caderinas/metabolismo , Derme/efeitos dos fármacos , Derme/enzimologia , Orelha/patologia , Humanos , Inflamação/patologia , Interleucina-10/biossíntese , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Projetos Piloto , Resveratrol/farmacologia , Staphylococcus aureus/efeitos dos fármacos
6.
Exp Cell Res ; 388(2): 111816, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31923426

RESUMO

Lymphedema is a chronic progressive disease ultimately resulting in severe, disfiguring swelling and permanent changes of the affected tissues. Presently, there is no causal treatment approach of lymphedema. Therefore, most therapies are purely symptomatic. However, the recent use of stem cell-based therapies has offered new prospects for alternative treatment options. The present study was performed to investigate the effects of human adipose-derived stem cells (ADSCs) on human dermal lymphatic endothelial cells (HDLECs) in terms of basic in vitro lymphangiogenic assays (WST-8 assay, scratch assay, transmigration assay, sprouting assay, tube formation assay). The influence of ADSC-conditioned medium (ADSC-CM) on HDLECs was compared to recombinant VEGF-C, bFGF and HGF. Further ADSC-CM was characterized by protein microarray and enzyme-linked immunosorbent assay (ELISA). Although key-lymphangiogenic growth factors - like VEGF-C - could only be detected in low concentrations within the conditioned medium (CM), HDLECs were potently stimulated to proliferate, migrate and to form tube like structures by ADSC-CM. Despite concentrations more than hundredfold higher than those found in the conditioned medium, stimulation with recombinant VEGF-C, bFGF and HGF was still weaker compared to ADSC-CM. These results highlight the effectiveness of growth factors secreted by ADSC to stimulate HDLEC, potentially providing a promising new therapeutic approach for the treatment of lymphedema.


Assuntos
Proliferação de Células , Derme/citologia , Células Endoteliais/citologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfangiogênese , Células-Tronco Mesenquimais/citologia , Movimento Celular , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Derme/efeitos dos fármacos , Derme/metabolismo , Células Endoteliais/metabolismo , Humanos , Técnicas In Vitro , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo
7.
Arthritis Res Ther ; 21(1): 290, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842999

RESUMO

BACKGROUND: Systemic sclerosis is a multisystem inflammatory and vascular lesion leading to extensive tissue fibrosis. A reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, DZ2002, modulates the pathologic processes of various inflammatory diseases and autoimmune diseases. This study is designed to investigate the therapeutic potentiality of DZ2002 for experimental systemic sclerosis models. METHODS: The anti-inflammatory and anti-fibrotic features of DZ2002 and its mechanisms were investigated in a bleomycin (BLM)-induced dermal fibrosis mice model. The effects of DZ2002 on expression of extracellular matrix components and TGF-ß signaling in human dermal fibroblasts were analyzed. Simultaneously, the effects of DZ2002 on macrophage activation and endothelial cell adhesion molecule expression were also evaluated. RESULTS: DZ2002 significantly attenuated dermal fibrosis in BLM-induced mice. Consistently, DZ2002 inhibited the expression of various molecules associated with dermal fibrosis, including transforming growth factor ß1, connective tissue growth factor, tumor necrosis factor-α, interferon-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12p40, IL-17A, and monocyte chemotactic protein 1 in the lesional skin of BLM-induced mice. Furthermore, DZ2002 decreased the proportion of macrophages, neutrophils, and T cells (especially T helper cells) in the skin tissue of BLM-induced mice. In addition, DZ2002 attenuated both M1 macrophage and M2 macrophage differentiation in vivo and in vitro. Importantly, DZ2002 directly reversed the profibrotic phenotype of transforming growth factor-ß1-treated dermal fibroblasts and suppressed ICAM-1, VCAM-1, VEGF, bFGF, and ET-1 expression in endothelial cells. Finally, our investigations showed that DZ2002 relieved systemic sclerosis by regulating fibrosis TGF-ß/Smad signaling pathway. CONCLUSIONS: DZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types and would be a potential drug for the treatment of systemic sclerosis.


Assuntos
Adenina/análogos & derivados , Butiratos/farmacologia , Derme/efeitos dos fármacos , Inflamação/prevenção & controle , Escleroderma Sistêmico/prevenção & controle , Doenças Vasculares/prevenção & controle , Adenina/farmacologia , Animais , Bleomicina , Linhagem Celular , Células Cultivadas , Derme/metabolismo , Derme/patologia , Modelos Animais de Doenças , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose/induzido quimicamente , Fibrose/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/metabolismo , Macrófagos/classificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/metabolismo , Células THP-1 , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Doenças Vasculares/genética , Doenças Vasculares/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Cient. dent. (Ed. impr.) ; 16(3): 223-230, sept.-dic. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-185998

RESUMO

La aplicación de materiales de relleno como alternativa a las intervenciones quirúrgicas estéticas con el fin de corregir defectos faciales en la piel tales como arrugas o imperfecciones, es una práctica que cada vez es más demandada por los pacientes en el día a día en la consulta. Existen distintos materiales capaces de devolver a la piel ese volumen perdido con los años. Estos, se clasifican en función de su composición y de su duración. El ácido hialurónico es el material de relleno más empleado por los odontólogos al gozar de un gran éxito por ser efectivo y versátil además es un producto seguro, ya que sus posibles complicaciones son mínimas


The application of filling materials as an alternative to aesthetic surgical interventions, in order to correct facial defects in the skin, such as wrinkles or imperfections, is a practice that is increasingly demanded by patients on a day-to-day basis in the practice.There are several materials capable of returning the skin that volume lost over the years. These are classified according to their duration and duration.Hyaluronic acid is the most used filling material for dentists to enjoy great success because it is effective and versatile, it is also a safe product since it is possible to have minimal problems


Assuntos
Humanos , Ácido Hialurônico/uso terapêutico , Cirurgia Plástica/tendências , Odontologia/normas , Técnicas Cosméticas , Tecido Conjuntivo/efeitos dos fármacos , Colágeno , Derme/efeitos dos fármacos , Géis de Silicone , Legislação Odontológica
9.
Dermatol Surg ; 45(12): 1580-1584, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31765337

RESUMO

BACKGROUND: Little literature exits on the mechanism of action of implanted polymethylmethacrylate (PMMA) filler. OBJECTIVE: To characterize PMMA-induced dermal extracellular matrix production in the skin. MATERIALS AND METHODS: Single-center, open-label prospective study in healthy volunteers undergoing removal of redundant skin was injected intradermally and subdermally with PMMA dermal filler (Bellafill). Punch biopsies were harvested over a time course and evaluated for the deposition of collagen-3 and procollagen-1, proteoglycans and elastin using immunohistochemistry. Blinded histopathologic readings were performed by a dermatopathologist to characterize the nature of the dermal extracellular matrix findings. RESULTS: Normal inflammatory infiltrate was exhibited at all timepoints after PMMA injection with an influx of fibroblasts and new vasculature. Tissue proteoglycans were noted within the injectate beginning at Week 1 and persisted through the study end point. Increased collagen Type 3 was evident following the first week after injection, peaked at Month 2 and diminished through Months 3 through 6. Procollagen-1 was noted at Month 1 and continued to increase in intensity and organization through the study end point (6 months). Elastin staining was inconclusive. Polymethylmethacrylate microspheres remained within the initial injection area and became encapsulated within new collagen fibers. The growth and pattern of new connective tissue mimicked a normal wound healing response. CONCLUSION: Polymethylmethacrylate-collagen gel filler stimulates collagen-3 and procollagen-1 when injected into human skin. This combination of neocollagenesis followed by microencapsulation of PMMA microspheres in the new tissue provides for long-lasting results.


Assuntos
Colágeno Tipo III/biossíntese , Colágeno Tipo I/biossíntese , Colágeno/administração & dosagem , Preenchedores Dérmicos/administração & dosagem , Derme/efeitos dos fármacos , Polimetil Metacrilato/administração & dosagem , Adulto , Biópsia , Derme/citologia , Derme/metabolismo , Elastina/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Injeções Intradérmicas , Microesferas , Pessoa de Meia-Idade , Estudos Prospectivos , Proteoglicanas/metabolismo
10.
Int J Pharm ; 572: 118793, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715350

RESUMO

Dermal administration of different macromolecules, such as nucleic acids, remains a real challenge because of the difficulty of crossing the main skin barrier, the stratum corneum (SC). To overcome this barrier, the use of deformable lipid-based nanovectors were developed to increase topical penetration through the SC and to promote the intercellular delivery of drugs. The purpose of this study is to compare the skin penetration of different liposome formulations according to their composition. In vitro and ex vivo experiments using Franz diffusion cells were performed to highlight the effect of (i) lipid charge, (ii) edge activators (EA) and (iii) ethanol on the diffusion properties of nanovectors. We showed that all formulations were not able to cross the SC. However, on a tape stripped skin, we showed that cationic formulations containing an EA and ethanol improved the skin penetration. The use of microneedles was considered to bypass the SC. We have shown that sodium cholate and ethanol were necessary to ensure an appropriate diffusion of liposomes into the dermis when applied by means of microneedles. This could be a promising approach to further deliver efficiently macromolecules such as genes into the skin.


Assuntos
Derme/metabolismo , Etanol/química , Metabolismo dos Lipídeos , Lipídeos/química , Agulhas , Absorção Cutânea , Administração Cutânea , Animais , Derme/efeitos dos fármacos , Desenho de Equipamento , Etanol/farmacologia , Técnicas de Transferência de Genes , Lipossomos , Miniaturização , Absorção Cutânea/efeitos dos fármacos , Sus scrofa
11.
Sci Rep ; 9(1): 16903, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729428

RESUMO

The Trapa japonica fruit is a natural plant growing in ponds with its roots in the mud. It has long been used as a home remedy for many diseases; however, a major problem with this kind of natural extract is the multicomponents-multitargets for diseases. Such problems make it difficult to identify the mechanism of action. Another problem is quality control and consistency. The aim of this research was to isolate a single bioactive compound (peptide) derived from the Trapa japonica fruit. The research was conducted with various experimental techniques, such as fermentation and liquid chromatography, to isolate a peptide. We isolated the AC 2 peptide from Trapa japonica fruit and found it to be promising on human dermal papilla cells. Dihydrotestosterone (DHT) stresses human dermal papilla cells and is a major cause of hair loss resulting from hormones and environmental factors. The purpose of this research was to develop an understanding of the mechanism by which the AC 2 peptide rescues dihydrotestosterone (DHT)-treated human dermal papilla cells. We explored the effects of the AC 2 peptide on the cell biological functions of human dermal papilla cells (HDPs). HDPs were treated with the AC 2 peptide and DHT. Then, a cytotoxicity assay, flow cytometry, Western blot, immunoprecipitation, and 3D cell culture for immunohistochemistry were conducted to investigate the mTORC1 pathway and suppression of autophagy and apoptosis. In addition, we also synthesized the AC2 peptide as an alternative to the expensive and difficult isolation and purification procedures and confirmed its potential in biomedical applications. We also validated the effects of the synthetic AC2 peptide as well as the isolated and purified AC2 peptide and established their similarity. Although extensive research has been carried out on natural extracts, few single studies have isolated and separated a bioactive peptide (single compound).


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Bacillus/fisiologia , Di-Hidrotestosterona/farmacologia , Folículo Piloso/efeitos dos fármacos , Lythraceae/química , Extratos Vegetais/farmacologia , Alopecia/metabolismo , Alopecia/patologia , Alopecia/prevenção & controle , Células Cultivadas , Citoproteção/efeitos dos fármacos , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Frutas/química , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Humanos , Lythraceae/microbiologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Extratos Vegetais/química , Couro Cabeludo/citologia , Couro Cabeludo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
12.
Sci Rep ; 9(1): 17008, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740717

RESUMO

Shikimic acid (SA) has recently been found to be a major component of plant stem cells. The exact effects of SA on human hair follicles (HFs) is unknown. The purpose of this study was to examine the effects of SA on hair growth. We investigated the effect of SA on an in vivo C57BL/6 mouse model. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. SA significantly prolonged anagen hair growth in the in vivo mouse model. We confirmed expression of the MR in human HFs, and that SA increased the proliferation of hDPCs and hORSCs. It was found that SA enhanced hair shaft elongation in an ex vivo human hair organ culture. SA treatment of hDPCs led to increased c-myc, hepatocyte growth factor, keratinocyte growth factor and vascular endothelial growth factor levels and upregulation of p38 MAPK and cAMP response element-binding protein levels. Our results show that SA promotes hair growth and may serve as a new therapeutic agent in the treatment of alopecia.


Assuntos
Derme/metabolismo , Folículo Piloso/metabolismo , Cabelo/metabolismo , Ácido Chiquímico/metabolismo , Alopecia/genética , Alopecia/metabolismo , Alopecia/prevenção & controle , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Derme/citologia , Derme/efeitos dos fármacos , Feminino , Fator 7 de Crescimento de Fibroblastos/metabolismo , Expressão Gênica/efeitos dos fármacos , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/genética , Lectinas de Ligação a Manose/metabolismo , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Ácido Chiquímico/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
J Microbiol Biotechnol ; 29(11): 1830-1840, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31601058

RESUMO

Loliolide is one of the most ubiquitous monoterpenoid compounds found in algae, and its potential therapeutic effect on various dermatological conditions via agent-induced biological functions, including anti-oxidative and anti-apoptotic properties, was demonstrated. Here, we investigated the effects of loliolide on hair growth in dermal papilla (DP) cells, the main components regulating hair growth and loss conditions. For this purpose, we used a threedimensional (3D) DP spheroid model that mimics the in vivo hair follicle system. Biochemical assays showed that low doses of loliolide increased the viability and size of 3D DP spheroids in a dose-dependent manner. This result correlated with increases in expression levels of hair growth-related autocrine factors including VEGF, IGF-1, and KGF. Immunoblotting and luciferase-reporter assays further revealed that loliolide induced AKT phosphorylation, and this effect led to stabilization of ß-catenin, which plays a crucial role in the hair-inductive properties of DP cells. Further experiments showed that loliolide increased the expression levels of the DP signature genes, ALP, BMP2, VCAN, and HEY1. Furthermore, conditioned media from loliolide-treated DP spheroids significantly enhanced proliferation and the expression of hair growth regulatory genes in keratinocytes. These results suggested that loliolide could function in the hair growth inductivity of DP cells via the AKT/ ß-catenin signaling pathways.


Assuntos
Benzofuranos/farmacologia , Derme/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Derme/citologia , Células HEK293 , Folículo Piloso/crescimento & desenvolvimento , Humanos , Queratinócitos/efeitos dos fármacos , Monoterpenos/farmacologia , Fosforilação/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
14.
Macromol Biosci ; 19(12): e1900207, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31657524

RESUMO

Poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation is widely used to prepare coacervate particles by electrostatic complexation with an anionic heparin (HEP) in aqueous environments, for controlled release of therapeutic proteins. However, coacervate complexes aggregate randomly due to particle-particle charge interactions. Herein, a new term "coacersome" is introduced to represent a stable polyplex formed by complexation of mPEGylated PEAD and HEP. Methoxy polyethylene glycol (mPEG)-b-cationic PEAD diblock copolymers are synthesized and complexed with HEP to create a stable "coacersome" structure. Water-soluble mPEG moiety assembles on the surface of coacersomes in aqueous conditions and creates a steric barrier to avoid aggregation of coacersomes. The coacersomes are able to maintain their initial spherical morphology and size for longer durations in the presence of competing ions, such as 0.3 m NaCl. Additionally, the coacersomes exhibit biocompatibility toward human dermal fibroblasts, a high loading efficiency (>96%) for encapsulation of bone morphogenetic protein 2 (BMP-2), and a sustained release profile up to 28 days. The BMP-2-loaded coacersomes further exhibit increased osteogenic differentiation of human mesenchymal stem cells (hMSCs). The developed coacersome structures have the potential to be utilized as effective carriers for therapeutic protein delivery.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Heparina/química , Oligopeptídeos/farmacologia , Polietilenoglicóis/química , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Coloides , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Cinética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Oligopeptídeos/síntese química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Tamanho da Partícula , Polieletrólitos/química
15.
Int J Mol Med ; 44(5): 1629-1640, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545472

RESUMO

Stem cells derived from human amniotic membrane (hAM) are promising targets in regenerative medicine. A previous study focused on human amniotic stem cells in skin wound and scar­free healing. The present study aimed to investigate whether hydrogen peroxide (H2O2)­induced senescence of human dermal fibroblasts (hDFs) was influenced by the anti­aging effect of conditioned medium (CdM) derived from human amniotic stem cells. First, the biological function of two types of amniotic stem cells, namely human amniotic epithelial cells (hAECs) and human amniotic mesenchymal stem cells (hAMSCs), on hDFs was compared. The results of cell proliferation and wound healing assays showed that CdM promoted cell proliferation and migration. In addition, CdM from hAECs and hAMSCs significantly promoted proliferation of senescent hDFs induced by H2O2. These results indicated that CdM protects cells from damage caused by H2O2. Treatment with CdM decreased senescence­associated ß­galactosidase activity and improved the entry of proliferating cells into the S phase. Simultaneously, it was found that CdM increased the activity of superoxide dismutase and catalase and decreased malondialdehyde by reducing H2O2­induced intracellular reactive oxygen species production. It was found that CdM downregulated H2O2­stimulated 8­hydroxydeoxyguanosine and γ­H2AX levels and decreased the expression of the senescence­associated proteins p21 and p16. In conclusion, the findings indicated that the paracrine effects derived from human amniotic stem cells aided delaying oxidative stress­induced premature senescence.


Assuntos
Âmnio/metabolismo , Senescência Celular/fisiologia , Meios de Cultivo Condicionados/metabolismo , Derme/metabolismo , Fibroblastos/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Derme/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Malondialdeído/metabolismo , Células-Tronco Mesenquimais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fase S/fisiologia , Pele/efeitos dos fármacos , Pele/metabolismo , Superóxido Dismutase/metabolismo , Cicatrização/fisiologia
16.
Macromol Biosci ; 19(11): e1900181, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31531939

RESUMO

Freestanding multilayer films prepared by layer-by-layer technique have attracted interest as promising materials for wound dressings. The goal is to fabricate freestanding films using chitosan (CHI) and alginate (ALG) including subsequent crosslinking to improve the mechanical properties of films while maintaining their biocompatibility. Three crosslinking strategies are investigated, namely use of calcium ions for crosslinking ALG, 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide combined with N-hydroxysuccinimide for crosslinking ALG with CHI, and Genipin for crosslinking chitosan inside the films. Different characteristics, such as surface morphology, wettability, swelling, roughness, and mechanical properties are investigated showing that films became thinner, exhibited rougher surfaces, had lower water uptake, and increased mechanical strength after crosslinking. Changes of wettability are moderate and dependent on the crosslinking method. In vitro cytotoxicity and cell attachment studies with human dermal fibroblasts show that freestanding CHI-ALG films represent a poorly adhesive substratum for fibroblasts, while studies using incubation of plastic-adherent fibroblast beneath floating films show no signs of cytotoxicity in a time frame of 7 days. Results from cell experiments combined with film characteristics after crosslinking, indicate that crosslinked freestanding films made of ALG and CHI may be interesting candidates for wound dressings.


Assuntos
Alginatos/química , Bandagens , Quitosana/química , Materiais Revestidos Biocompatíveis/síntese química , Reagentes para Ligações Cruzadas/farmacologia , Polímeros/síntese química , Adesivos/síntese química , Adesivos/química , Alginatos/síntese química , Alginatos/farmacologia , Fenômenos Biomecânicos/efeitos dos fármacos , Células Cultivadas , Quitosana/síntese química , Quitosana/farmacologia , Materiais Revestidos Biocompatíveis/química , Reagentes para Ligações Cruzadas/química , Derme/citologia , Derme/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Humanos , Teste de Materiais , Membranas Artificiais , Polímeros/química , Molhabilidade/efeitos dos fármacos
17.
Sci Rep ; 9(1): 12994, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506448

RESUMO

With recent approvals of antisense oligonucleotides as therapeutics, there is an increasing interest in expanding the application of these compounds to many other diseases. Our laboratory focuses on developing therapeutic splice modulating antisense oligonucleotides to treat diseases potentially amendable to intervention during pre-mRNA processing, and here we report the use of oligomers to down-regulate integrin alpha 4 protein levels. Over one hundred antisense oligonucleotides were designed to induce skipping of individual exons of the ITGA4 transcript and thereby reducing protein expression. Integrin alpha 4-mediated activities were evaluated in human dermal fibroblasts and Jurkat cells, an immortalised human T lymphocyte cell line. Peptide conjugated phosphorodiamidate morpholino antisense oligomers targeting ITGA4 were also assessed for their effect in delaying disease progression in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. With the promising results in ameliorating disease progression, we are optimistic that the candidate oligomer may also be applicable to many other diseases associated with integrin alpha 4 mediated inflammation. This highly specific strategy to down-regulate protein expression through interfering with normal exon selection during pre-mRNA processing should be applicable to many other gene targets that undergo splicing during expression.


Assuntos
Derme/efeitos dos fármacos , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/terapia , Terapia Genética , Integrinas/antagonistas & inibidores , Oligonucleotídeos Antissenso/farmacologia , Processamento de RNA/efeitos dos fármacos , Animais , Adesão Celular , Movimento Celular , Derme/metabolismo , Derme/patologia , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Integrinas/genética , Células Jurkat , Camundongos , Camundongos Endogâmicos C57BL , Oligonucleotídeos Antissenso/genética , Processamento de RNA/genética
18.
Biofactors ; 45(6): 950-958, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520488

RESUMO

The regeneration of proliferation potential of dermal papilla (DP) cells contributes to the treatment of hair loss disorders. Ginkgolide B (GKB) and bilobalide (BB) are two functional components isolated from Ginkgo biloba that can promote hair growth. In the current study, the effect of GKB or BB on DP cell viability and the related signaling was assessed. Hair follicles were isolated from minks, and the growth of hair follicles was measured under the administration of GKB or BB. DP cells isolated from minks were also subjected to GKB or BB. The administration of GKB or BB induced the growth of hair follicles. The viability of DP cells was also increased by GKB or BB as illustrated by methyl thiazolyl tetrazolium and flow cytometry detection. Moreover, the secretion of VEGF was enhanced by GKB or BB. At molecular level, the activities of Akt, ERK1/2, and ß-catenin were induced by GKB, whereas BB only increased the activities of Akt and ß-catenin. In conclusion, although the two components influenced the ß-catenin signaling activity in distinct mechanisms, they both increased the viability of DP cells and promoted the cycle of hair follicles.


Assuntos
Ciclopentanos/farmacologia , Furanos/farmacologia , Ginkgolídeos/farmacologia , Folículo Piloso/crescimento & desenvolvimento , Lactonas/farmacologia , Vison/crescimento & desenvolvimento , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclopentanos/química , Derme/efeitos dos fármacos , Derme/crescimento & desenvolvimento , Furanos/química , Ginkgo biloba/química , Ginkgolídeos/química , Folículo Piloso/efeitos dos fármacos , Lactonas/química , Transdução de Sinais/efeitos dos fármacos , beta Catenina/genética
19.
Colloids Surf B Biointerfaces ; 183: 110409, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386933

RESUMO

The objective of present study was to develop and evaluate lipid vesicular transdermal system of iloperidone. Liposomes were prepared successfully using thin film hydration method. With aim of enhancing permeation, cholesterol from liposomes was replaced with transcutol to give PEVs. Liposomes and PEVs were evaluated for particle size, shape, entrapment efficiency, viscosity and release study. The vesicles were incorporated in 0.5% of Carbopol gel and evaluated. Particle size of liposomes and PEVs was found between 200-300 nm and entrapment efficiency was found 80-90%w/w. The transdermal gels were homogeneous, spreadable having acceptable pH and drug content between 90-100%.In ex vivo studies, both liposomes and PEVs showed relatively higher skin deposition and permeation of Iloperidone than the plain drug without vesicles. The in vivo pharmacokinetics studies showed relative bioavailability of the PEV loaded gel as 62% and 166% when compared to the oral drug and gel without vesicles respectively. Pharmacodynamic studies showed FRT and HRT delay responses of the transdermal gel systems were significant[p < 0.05] as compared to control at the end of 24 hs. Thus, it can be concluded that transdermal delivery system can be a promising approach for sustained delivery of Iloperidone.


Assuntos
Antipsicóticos/farmacocinética , Derme/metabolismo , Composição de Medicamentos/métodos , Isoxazóis/farmacocinética , Lipossomos/farmacocinética , Piperidinas/farmacocinética , Resinas Acrílicas/química , Administração Cutânea , Animais , Antipsicóticos/química , Disponibilidade Biológica , Colesterol/química , Derme/efeitos dos fármacos , Orelha , Etilenoglicóis/química , Géis , Isoxazóis/química , Lipossomos/síntese química , Tamanho da Partícula , Permeabilidade , Piperidinas/química , Ratos , Ratos Wistar , Absorção Cutânea/fisiologia , Suínos
20.
Int J Nanomedicine ; 14: 5381-5396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409994

RESUMO

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.


Assuntos
Derme/metabolismo , Lipídeos/química , Nanopartículas/química , Tacrolimo/farmacologia , Temperatura , Administração Cutânea , Animais , Varredura Diferencial de Calorimetria , Derme/efeitos dos fármacos , Liberação Controlada de Fármacos , Irritantes/toxicidade , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Ratos Sprague-Dawley , Absorção Cutânea/efeitos dos fármacos , Testes Cutâneos , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Difração de Raios X
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