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2.
Int. j. morphol ; 38(1): 96-100, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056404

RESUMO

During aging, usually graying of the hair occurs as a result of oxidative stress. Driven by social acceptance and self-perception of the exterior appearance, both men and women rely on hair dyeing products, in order to mask the graying hair. At the same time, a frequent use of synthetic products and treatment can damage the hair shaft; for this reason, this study aimed to evaluate the morphological effect of the herbal dye derived from Lawsonia inermis (henna), on hair. Dyed hairs were evaluated by means of SEM. Subsequently, they were compared, qualitatively and quantitatively, with undyed hairs. Results showed a positive impact on the cuticula pattern and on the diameters of the examined samples, after henna application. Different results, about the degree and the type of morphological changes occurring on pigmented hairs, may depend on the phenotype and on the health condition of hair, before dye treatment.


Durante el envejecimiento, generalmente se produce el envejecimiento del cabello como resultado del estrés oxidativo. Motivados por la aceptación social y la autopercepción de la apariencia, tanto hombres como mujeres confían en productos para teñir el cabello para enmascarar las canas. Al mismo tiempo, el uso frecuente de productos y tratamientos sintéticos puede dañar el tallo del cabello. Por esta razón, este estudio tuvo como objetivo evaluar el efecto morfológico del tinte derivado de Lawsonia inermis (henna) en el cabello. Los cabellos teñidos se evaluaron mediante SEM. Posteriormente, se compararon, cualitativa y cuantitativamente, con cabellos sin teñir. Los resultados mostraron un impacto positivo en el patrón de la cutícula y en los diámetros de las muestras examinadas, después de la aplicación de henna. Los diferentes resultados, sobre el grado y el tipo de cambios morfológicos que ocurren en los cabellos pigmentados, pueden depender del fenotipo y del estado de salud del cabello, antes del tratamiento con tinte.


Assuntos
Humanos , Microscopia Eletrônica de Varredura , Folículo Piloso/efeitos dos fármacos , Lawsonia (Planta) , Tinturas para Cabelo/farmacologia , Folículo Piloso/ultraestrutura , Cabelo/efeitos dos fármacos , Cabelo/ultraestrutura
4.
BMC Complement Altern Med ; 19(1): 372, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847849

RESUMO

BACKGROUND: Vernonia anthelmintica (L.) willd is a traditional urgur herb in China for a long history. Its alcohol extract (AVE) has been proved to promote hair follicle growth in C57BL/6 mice. We conducted this study to investigate the hair-growth effects of AVE in stressed mice and its possible mechanism of action. METHODS: The hair-follicle growth effects of AVE were examined by in vivo and in vitro study. We exposed C57BL/6 male mice to chronic restraint stress to induce murine hair follicle growth inhibition. The effects of AVE were examined by histological analysis, immunofluorescence for Ki67 and cytokeratin 19 immunoreactivity, western blot assay in tyrosinase and related proteins expressions and immunofluorescence for nerve fibers. In organ culture of mouse vibrissae follicles, we used substance P as a catagen-inducing factor of hair follicle growth, and measured the elongation of hair shafts and expression of neurokinin-1 receptor protein by application of AVE. RESULTS: Our results showed that AVE counteract murine hair follicle growth inhibition caused by chronic restraint stress via inducing the conversion of telogen to anagen and inhibiting catagen premature, increasing bulb keratinocytes and bulge stem cells proliferation, promoting melanogenesis, and reducing the numbers of substance P and calcitonin gene-related peptide nerve fibers. Furthermore, AVE also counteracted murine hair follicle growth inhibition caused by substance P in organ culture. CONCLUSION: These results suggest that AVE counteract stress-induced hair follicle growth inhibition in C57BL/6 mice in vivo and in vitro, and may be an effective new candidate for treatment of stress-induced hair loss.


Assuntos
Folículo Piloso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Vernonia , Animais , Folículo Piloso/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Restrição Física
5.
Int J Nanomedicine ; 14: 8409-8419, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695374

RESUMO

Introduction: Hair growth-promoting herbal extract mixtures (4HGF) exhibits significant anti-inflammatory activities relevant to promoting hair growth; however, its efficacy in patients with hair loss has been limited majorly due to its low penetration ability into hair follicles. Herein, we prepared hydrogels via dropwise addition of poly(γ-glutamic acid) (PGA) solution containing 4HGF into chitosan (CS) solution, resulting in quick formation of ~400 nm-sized hydrogel particles through electrostatic interaction-derived ionic gelation with over 50% encapsulation efficiency of 4HGF (PGA-4HGF). Methods: The size and morphology of PGA-4HGF were characterized by TEM, SEM, and dynamic light scattering analyses. Encapsulation efficiency and loading capacity of 4HGF within PGA-4HGF, as well as in vitro release profiles were determined by simply measuring the characteristic absorbance of 4HGF. Penetrating efficiency of PGA-4HGF was evaluated by tracking the respective fluorescence through model porcine skin with confocal laser microscope system. By treating PGA-4HGF on telogenic mice and dermal papilla cells (DPCs), we evaluated the size of hair bulbs in mice, as well as morphological changes in DPCs. Results: Negligible and sustained release of entrapped 4HGF from the hydrogel nanoparticles were observed under acidic and physiological pH conditions, respectively, which is quite advantageous to control their release and prolong their hair growth-promoting effect. The hydrogel nanoparticles were penetrable through the porcine skin after incubation with or without shaking. After treating telogenic mice and DPCs with PGA-4HGF, we detected enlargement of hair bulbs and remarkable shape changes, respectively, thereby showing its potential in induction of hair growth. Conclusion: These results suggest that the hydrogel nanoparticle formulation developed in this study can be employed as a potential approach for the preservation of hair growth-promoting compounds, their delivery of into hair follicles, and enhancing hair growth.


Assuntos
Quitosana/química , Fermentação , Folículo Piloso/crescimento & desenvolvimento , Hidrogéis/química , Nanopartículas/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ácido Poliglutâmico/análogos & derivados , Animais , Compostos de Bifenilo/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Depuradores de Radicais Livres/farmacologia , Folículo Piloso/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Tamanho da Partícula , Picratos/química , Ácido Poliglutâmico/química , Temperatura
6.
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
7.
Int J Nanomedicine ; 14: 7921-7931, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632009

RESUMO

Purpose: We designed formulations based on minoxidil (MXD) nanoparticles (N-MXD) and examined whether N-MXD can increase drug delivery into the follicles. In addition, we investigated the effect of N-MXD on hair growth in C57BL/6 mice. Methods: N-MXD (1%) was prepared as follows: methylcellulose, p-hydroxyalkylbenzoates, mannitol, and MXD were dispersed in purified water and milled using zirconia beads under refrigeration (5500 rpm, 30 s×15 times, intermittent milling). C57BL/6 mice were used to evaluate hair-growth effects. The expression levels of mRNA and protein for vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were determined by real-time PCR and ELISA methods, respectively. Results: The ratio of solid-MXD was approximately 60% in N-MXD, and the MXD nanoparticles (90-300 nm) were oblong in shape. For the design of nanomedicines, usability is important. Therefore, we measured the stability and toxicity after N-MXD treatment. No agglutination of MXD nanoparticles was detected for 2 weeks, and no redness or MXD powder residue was observed in the skin after repetitive applications of N-MXD. Next, we evaluated hair-growth effects by N-MXD treatment. MXD contents in the skin tissue from N-MXD were lower than for commercially available MXD formulations (CA-MXD). Conversely, MXD contents in the hair bulbs were higher for N-MXD than for CA-MXD, and the drug efficacy of N-MXD was also higher than that of CA-MXD. In addition, the mRNA and protein levels of IGF-1 and VEGF were enhanced by the repetitive application of N-MXD and CA-MXD, and the enhanced IGF-1 and VEGF levels were significantly higher for N-MXD than for CA-MXD. Conclusion: We designed a novel nanomedicine based on MXD nanoparticles and showed that N-MXD can deliver MXD into hair bulbs via hair follicles and that the therapeutic efficiency for hair growth is higher than for CA-MXD (solution type).


Assuntos
Sistemas de Liberação de Medicamentos , Cabelo/crescimento & desenvolvimento , Minoxidil/administração & dosagem , Minoxidil/farmacologia , Nanopartículas/química , Animais , Cabelo/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Minoxidil/sangue , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/efeitos dos fármacos , Solubilidade , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Biol Pharm Bull ; 42(9): 1446-1449, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474706

RESUMO

During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.


Assuntos
Flavonoides/farmacologia , Cor de Cabelo , Folículo Piloso/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Pele/lesões , Cicatrização/efeitos dos fármacos , Animais , Células Epidérmicas/efeitos dos fármacos , Células Epidérmicas/fisiologia , Flavonoides/química , Folículo Piloso/fisiologia , Luteolina/química , Luteolina/farmacologia , Melanócitos/efeitos dos fármacos , Melanócitos/fisiologia , Camundongos Endogâmicos C57BL , Pele/efeitos dos fármacos , Relação Estrutura-Atividade
10.
Int J Mol Sci ; 20(14)2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337050

RESUMO

Poly-γ-glutamic acid (γ-PGA)-based nanoparticles draw remarkable attention as drug delivery agents due to their controlled release characteristics, low toxicity, and biocompatibility. 4HGF is an herbal mixture of Phellinus linteus grown on germinated brown rice, Cordyceps militaris grown on germinated soybeans, Polygonum multiflorum, Ficus carica, and Cocos nucifera oil. Here, we encapsulated 4HGF within PGA-based hydrogel nanoparticles, prepared by simple ionic gelation with chitosan, to facilitate its penetration into hair follicles (HFs). In this study, we report the hair promoting activity of 4HGF encapsulated with PGA nanoparticles (PGA-4HGF) and their mechanism, compared to 4HGF alone. The average size of spherical nanoparticles was ~400 nm in diameter. Continuous release of PGA-4HGF was observed in a simulated physiological condition. As expected, PGA-4HGF treatment increased hair length, induced earlier anagen initiation, and elongated the duration of the anagen phase in C57BL/6N mice, compared with free 4HGF treatment. PGA-4HGF significantly increased dermal papilla cell proliferation and induced cell cycle progression. PGA-4HGF also significantly increased the total amount of ß-catenin protein expression, a stimulator of the anagen phase, through induction of cyclinD1 and CDK4 protein levels, compared to free 4HGF treatment. Our findings underscore the potential of PGA nanocapsules to efficiently deliver 4HGF into HFs, hence promoting hair-growth. Therefore, PGA-4HGF nanoparticles may be promising therapeutic agents for hair growth disorders.


Assuntos
Portadores de Fármacos , Folículo Piloso/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Nanopartículas , Extratos Vegetais/farmacologia , Ácido Poliglutâmico/análogos & derivados , Animais , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Humanos , Camundongos , Camundongos Transgênicos , Nanopartículas/química , Nanopartículas/ultraestrutura , Extratos Vegetais/química , Ácido Poliglutâmico/química , Via de Sinalização Wnt/efeitos dos fármacos
11.
Skin Res Technol ; 25(5): 701-711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31206839

RESUMO

BACKGROUND: Biopsy-based "reversal hypothesis" claimed conversion of miniaturized hair follicles into terminal ones for the improvement of male pattern hair loss (MPHL) with FDA-approved drugs. MATERIALS AND METHODS: MPHL volunteers (n = 13) completed a 24-month phototrichogram study. After 2 months no-treatment, panellists took finasteride 1mg daily for 2 years. Hair changes from the best responder would explain the nature of improved hair growth. RESULTS: Due to the wide range of hair growth variables, no parameter was statistically significantly changed by finasteride in the group. Clinically there were 4 worse, 6 no change, 2 slightly and 1 moderately improved subject associated with turning telogen/empty terminal follicles into anagen after 12- and 24-month finasteride. From 113 miniaturized hair (diameters ≤ 30 µm) at baseline, 79 were still miniature hair after 2 years on finasteride. No hair were found at the remaining mapped sites except for 2 terminal hairs considered a probabilistic "uncertainty." CONCLUSION: Moderate hair improvement resulted from increased productivity of deficient terminal follicles, but not yet irreversibly affected at baseline without implication of miniaturized hair follicles. The latter further regressed even with oral intake of finasteride. The data suggest the rejection of the "reversal hypothesis" unless proven otherwise with duly validated methods.


Assuntos
Alopecia/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Finasterida/uso terapêutico , Cabelo/crescimento & desenvolvimento , Adulto , Cabelo/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Humanos , Masculino , Couro Cabeludo/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
12.
J Pharmacol Exp Ther ; 370(2): 299-307, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152005

RESUMO

Hair growth starts from hair follicles that reside in dermis, and abnormal hair growth is an early sign of hair follicle disease or systemic illness such as alopecia or hair loss. Therefore, identifying a target critical for dysfunctional hair follicles is fundamental to alleviating dermatologic or systemic diseases with hair abnormalities. The warm temperature-activated Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channel protein is abundantly expressed in the skin keratinocytes, and dysfunctional TRPV3 causes human congenital Olmsted syndrome, characterized by skin diseases and alopecia, indicating an important role for TRPV3 in hair follicle development and hair growth. To validate TRPV3 as a therapeutic target, we investigated the impact of pharmacological modulation of TRPV3 on hair growth using a combination of biochemical and cell biology, immunohistochemical, whole-cell patch clamp, RNA interference, and pharmacological approaches. We found that functional TRPV3 channel proteins are highly expressed in hair follicle outer root sheath (ORS) cells as detected by Western blot analysis, immunohistochemical staining, and electrophysiological techniques. Pharmacological activation of TRPV3 by agonist natural carvacrol induces cell death of ORS cells, and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Conversely, specific inhibition of TRPV3 by inhibitor natural forsythoside B and short-hairpin RNA reverses the cell death induced by carvacrol-mediated TRPV3 activation in human ORS cells. Furthermore, forsythoside B results in a significant reversal of hair growth inhibition induced by agonist carvacrol. Altogether, our findings demonstrate that TRPV3 channel is critical for regulation of hair growth, and inhibition of TRPV3 may represent a promising therapy for hair loss or hair follicle-related skin diseases.


Assuntos
Morte Celular/efeitos dos fármacos , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Canais de Cátion TRPV/metabolismo , Temperatura , Animais , Ácidos Cafeicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Células HEK293 , Folículo Piloso/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
Int J Cosmet Sci ; 41(4): 332-345, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240739

RESUMO

It is known that hair growth disorders and hair loss can cause personal distress and affect well-being. Whilst clinical conditions remain a target for medical research, current research on hair follicle biology and hair growth control mechanisms also provides opportunities for a range of non-medical and cosmetic interventions that have a modulating effect on the scalp and follicle function. Furthermore, an improvement of the hair fibre characteristics (cuticle structure, cortex size and integrity) could add to the overall positive visual effect of the hair array. Since phytochemicals are a popular choice because of their traditional appeal, this review provides a critical evaluation of the available evidence of their activity for hair benefit, excluding data obtained from animal tests, and offers recommendations on improving study validity and the robustness of data collection in pre-clinical and clinical studies.


Assuntos
Alopecia/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Alopecia/fisiopatologia , Animais , Cabelo/crescimento & desenvolvimento , Folículo Piloso/efeitos dos fármacos , Humanos , Compostos Fitoquímicos/farmacologia
14.
PLoS One ; 14(5): e0216003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042749

RESUMO

Alopecia is a clinical condition caused by excessive hair loss which may result in baldness, the causes of which still remain elusive. Conditioned media (CM) from stem cells shows promise in regenerative medicine. Our aim was to evaluate the potential CM of dental pulp stem cells obtained from human deciduous teeth (SHED-CM) to stimulate hair growth under in vitro and in vivo conditions. SHED and hair follicle stem cells (HFSCs) (n = 3) were cultured in media combinations; i) STK2, ii) DMEM-KO+10% FBS, iii) STK2+2% FBS and profiled for the presence of positive hair growth-regulatory paracrine factors; SDF-1, HGF, VEGF-A, PDGF-BB and negative hair growth-regulatory paracrine factors; IL-1α, IL-1ß, TGF-ß, bFGF, TNF-α, and BDNF. The potential of CM from both cell sources to stimulate hair growth was evaluated based on the paracrine profile and measured dynamics of hair growth under in vitro conditions. The administration of CM media to telogen-staged synchronized 7-week old C3H/HeN female mice was carried out to study the potential of the CM to stimulate hair growth in vivo. SHED and HFSCs cultured in STK2 based media showed a shorter population doubling time, higher viability and better maintenance of MSC characteristics in comparison to cells cultured in DMEM-KO media. STK2 based CM contained only two negative hair growth-regulatory factors; TNF-α, IL-1 while DMEM-KO CM contained all negative hair growth-regulatory factors. The in vitro study confirmed that treatment with STK2 based media CM from passage 3 SHED and HFSCs resulted in a significantly higher number of anagen-staged hair follicles (p<0.05) and a significantly lower number of telogen-staged hair follicles (p<0.05). Administration of SHED-CM to C3H/HeN mice resulted in a significantly faster stimulation of hair growth in comparison to HFSC-CM (p<0.05), while the duration taken for complete hair coverage was similar for both CM sources. Thus, SHED-CM carries the potential to stimulate hair growth which can be used as a treatment tool for alopecia.


Assuntos
Alopecia/terapia , Meios de Cultivo Condicionados/farmacologia , Cabelo/efeitos dos fármacos , Células-Tronco Adultas/metabolismo , Animais , Polpa Dentária/patologia , Feminino , Cabelo/crescimento & desenvolvimento , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C3H
15.
Life Sci ; 229: 210-218, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102746

RESUMO

AIMS: Hair follicles play a critical role in the process of hair growth. The dermal papilla cells (DPCs) are an important component in the hair follicle regeneration and growth. This study investigated the effects of ginsenoside Rb1 on the growth of cultured mink hair follicles and DPCs. MAIN METHODS: The mink hair follicles were treated with ginsenoside Rb1 for 9 days and their lengths were measured every three days. Real-time PCR was used to determine the mRNA expression of vascularization endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGF-R2) and TGF-ß1. In addition, the levels of proteins were detected by western blot. Cell proliferation was determined by immunofluorescence staining of proliferation marker Ki-67 and cell cycle analysis was performed on flow cytometry. Moreover, cell migration was evaluated by wound healing assay. KEY FINDINGS: Ginsenoside Rb1 promoted the growth of hair follicles, and proliferation and migration of DPCs. Ginsenoside Rb1 improved the expression levels of VEGFA and VEGF-R2, while attenuated the TGF-ß1 expression both in hair follicles and DPCs. Furthermore, ginsenoside Rb1 facilitated the activation of PI3K/AKT/GSK-3ß signaling pathway in hair follicles and DPCs. SIGNIFICANCE: The results reveals a crucial role of PI3K/AKT/GSK-3ß signaling pathway in ginsenoside Rb1-induced growth of hair follicles and DPCs.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/genética , Folículo Piloso/efeitos dos fármacos , Masculino , Vison , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Cicatrização
16.
Skin Res Technol ; 25(5): 712-719, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31081179

RESUMO

BACKGROUND: Analytical measures for the pharmacodynamics understanding of drug induced scalp hair responses are lacking. MATERIALS AND METHODS: The present study measured in detail dynamics of hair productivity on two scalp test sites showing male pattern hair loss. The natural regression decay rate established after 2 years without treatment was followed by treatment with daily oral intake of 1 mg finasteride. RESULTS: While terminal hair (diameter ≥40 µm) were maintained "on-drug," within 30 months "off-drug" MPHL significantly worsened as 94% terminal hair miniaturised and became unproductive. Accordingly, the viable drug responding follicles were qualified as "finasteride dependent" unravelling a hereto unreported "rebound effect" after interruption of the drug intake. Interestingly, the transformation of terminal hair into miniaturised hair occurred only after 12 months without treatment, that is the time necessary to complete a clinically significant full hair cycle initiated during the drug intake. This explains why exogen hair release and miniaturisation occurred only between 12 and 30 months "off-drug" while resistant hair grew also slower. CONCLUSION: Drug dependency and rebound phenomenon are new findings along with evidence against the hypothesis claiming that terminal hair growth arises from initial vellus hair follicles in drug-treated MPHL.


Assuntos
Alopecia/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Finasterida/administração & dosagem , Cabelo/crescimento & desenvolvimento , Administração Oral , Fármacos Dermatológicos/farmacologia , Finasterida/farmacologia , Folículo Piloso/efeitos dos fármacos , Humanos , Masculino , Recidiva , Couro Cabeludo/efeitos dos fármacos
17.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970537

RESUMO

Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes (e.g., wound repair) of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Here we report that growing human hair follicles ex vivo in a defined GAG hydrogel mimicking the dermal matrix strongly promotes sustained cell survival and maintenance of a highly proliferative phenotype in the hair bulb and suprabulbar regions. This significant effect is associated with the activation of WNT/ß-catenin signaling targets (CCDN1, AXIN2) and with the expression of stem cell markers (CK15, CD34) and growth factors implicated in the telogen/anagen transition (TGFß2, FGF10). As a whole, these results point to the dermal GAG matrix as an important component in the regulation of the human hair follicle growth cycle, and to GAG-based hydrogels as potentially relevant modulators of this process both in vitro and in vivo.


Assuntos
Glicosaminoglicanos/farmacologia , Folículo Piloso/crescimento & desenvolvimento , Técnicas de Cultura de Tecidos/métodos , Biomarcadores/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosaminoglicanos/química , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Humanos , Hidrogéis/química , Via de Sinalização Wnt
18.
ACS Appl Mater Interfaces ; 11(19): 17270-17282, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30977624

RESUMO

Transdermal administration via skin appendages enables both localized and systemic drug delivery, as well as minimizes incidental toxicity. However, the design of an appropriate effective method for clinical use remains challenging. Here, we introduce calcium carbonate-based carriers for the transdermal transportation of bioactive substances. The proposed system presents easily manufacturable biodegradable particles with a large surface area enabling a high payload ability. Topical application of submicron porous CaCO3 particles in rats followed by the therapeutic ultrasound treatment results in their deep penetration through the skin along with plentiful filling of the hair follicles. Exploiting the loading capacity of the porous particles, we demonstrate efficient transportation of a fluorescent marker along the entire depth of the hair follicle down the bulb region. In vivo monitoring of the carrier degradation reveals the active dissolution/recrystallization of CaCO3 particles, resulting in their total resorption within 12 days. The proposed particulate system serves as an intrafollicular depot for drug storage and prolonged in situ release over this period. The urinary excretion profile proves the systemic absorption of the fluorescent marker. Hence, the elaborated transdermal delivery system looks promising for medical applications. The drug delivery to different target regions of the hair follicle may contribute to regenerative medicine, immunomodulation, and treatment of various skin disorders. In the meantime, the systemic uptake of the transported drug opens an avenue for prospective delivery routes beyond the scope of dermatology.


Assuntos
Plásticos Biodegradáveis/farmacologia , Carbonato de Cálcio/farmacologia , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Administração Cutânea , Animais , Plásticos Biodegradáveis/química , Carbonato de Cálcio/química , Portadores de Fármacos/química , Folículo Piloso/efeitos dos fármacos , Humanos , Ratos , Pele/efeitos dos fármacos
19.
Mol Brain ; 12(1): 31, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943999

RESUMO

Merkel discs, located in skin touch domes and whisker hair follicles, are tactile end organs essential for environmental exploration, social interaction, and tactile discrimination. Recent studies from our group and two others have shown that mechanical stimulation excites Merkel cells via Piezo2 channel activation to subsequently activate sensory neural pathways. We have further shown that mechanical stimulation leads to the release of 5-HT from Merkel cells to synaptically transmit tactile signals to whisker afferent nerves. However, a more recent study using skin touch domes has raised the possibility that Merkel discs are adrenergic synapses. It was proposed that norepinephrine is released from Merkel cells upon mechanical stimulation to subsequently activate ß2 adrenergic receptors on Merkel disc nerve endings leading to nerve impulses. In the present study, we examined effects of norepinephrine and ß2 adrenergic receptor antagonist ICI 118,551 on Merkel disc mechanoreceptors in mouse whisker hair follicles. We show that norepinephrine did not directly induce impulses from Merkel disc mechanoreceptors. Furthermore, we found that ICI 118,551 at 50 µM inhibited voltage-gated Na+ channels and suppressed impulses of Merkel disc mechanoreceptors, but ICI 118,551 at 1 µM had no effects on the impulse. These findings challenge the hypothesis of Merkel discs being adrenergic synapses.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Folículo Piloso/metabolismo , Mecanorreceptores/metabolismo , Células de Merkel/metabolismo , Norepinefrina/farmacologia , Propanolaminas/farmacologia , Sinapses/metabolismo , Vibrissas/efeitos dos fármacos , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/metabolismo , Animais , Folículo Piloso/efeitos dos fármacos , Células de Merkel/efeitos dos fármacos , Sinapses/efeitos dos fármacos
20.
Neurosci Lett ; 705: 14-19, 2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-30936034

RESUMO

Loss of the sense of touch or numbness in fingertips and toes is one of the earliest sensory dysfunctions in patients receiving chemotherapy with anti-cancer drugs such as vincristine. However, mechanisms underlying this chemotherapy-induced sensory dysfunction is poorly understood. Whisker hair follicles are tactile organs in non-primate mammals which are functionally equivalent to human fingertips. Here we used mouse whisker hair follicles as a model system to explore how vincristine treatment induces the loss of the sense of touch. We show that chronic treatment of mice with vincristine impaired in vivo whisker tactile behavioral responses. In vitro electrophysiological recordings made from whisker hair follicle afferent nerves showed that mechanically evoked whisker afferent impulses were significantly reduced following vincristine treatment. Furthermore, patch-clamp recordings from Merkel cells of whisker hair follicles revealed a significant reduction of mechanically activated currents via Piezo2 channels in Merkel cells. Collectively, our results suggest that Piezo2 channel dysfunction in Merkel cells contribute to the loss of the sense of touch following the chemotherapy treatment regimen with vincristine.


Assuntos
Folículo Piloso/efeitos dos fármacos , Canais Iônicos/metabolismo , Células de Merkel/efeitos dos fármacos , Tato/efeitos dos fármacos , Vincristina/efeitos adversos , Animais , Folículo Piloso/fisiologia , Técnicas In Vitro , Células de Merkel/fisiologia , Camundongos , Tato/fisiologia , Vibrissas/fisiologia
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