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1.
Biol Pharm Bull ; 42(10): 1665-1673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582654

RESUMO

Houttuynia cordata (HC) is a traditional oriental herbal medicinal plant widely used as a component of complex prescriptions in Asia for alopecia treatment. The effect of HC on hair growth and its underlying mechanism, however, have not been demonstrated or clarified. In this study, we investigated the hair growth promoting effect of HC in cultured human dermal papilla cells (hDPCs). HC extract was found to stimulate the proliferation of hDPCs and this stimulation might be in part a consequence of activated cellular energy metabolism, because treatment of HC extract increased the generation of nicotinamide adenine dinucleotide (NADH) and ATP through increasing the mitochondrial membrane potential (ΔΨ). In the context of cell cycle, HC extract increased the expression of CDK4 and decreased the expression of CCNA2 and CCNB1, implying that HC extract might induce G1 phase progression of DPCs which resulted in enhanced proliferation. HC extract increased the expression of Bcl2 essential for maintaining hair follicle anagen stage and cell survival. On the contrary, the expression of p16 and p21 was down-regulated by HC extract. In addition, HC extract enhanced the secretion of platelet-derived growth factor (PDGF)-aa and vascular endothelial growth factor (VEGF) and induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Furthermore, HC extract prolonged anagen stage in organ cultured human hair follicles. Our data strongly suggest that HC extract could support hair growth by stimulating proliferation of DPCs and elongating anagen stage, resulted from enhanced cellular energy metabolism and modulation of gene expression related to cell cycle, apoptosis, and growth factors.


Assuntos
Folículo Piloso/citologia , Cabelo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saururaceae , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Cabelo/crescimento & desenvolvimento , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
2.
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
3.
Cutis ; 104(1): 17-24, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31487342

RESUMO

Patterned hair loss is common and can negatively impact quality of life. Patients often seek nonsurgical treatment options as a first-line measure to avoid undue risks and expense associated with surgery. This article discusses these noninvasive treatment options, with a focus on minoxidil, finasteride, dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, and oral supplements.


Assuntos
Alopecia/terapia , Cabelo/crescimento & desenvolvimento , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Agulhas , Plasma Rico em Plaquetas , Qualidade de Vida
4.
J Ethnopharmacol ; 245: 112159, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31419502

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In French Polynesia, embellishment of the hair and skin is an important cultural and everyday practice. Yet, little research has focused on traditional preparations used for beautification in this region and their potential development as innovative cosmetic ingredients. AIM OF THE STUDY: In this present study we aim to assess and compile the ethnocosmetic potential of plants of French Polynesia to select and further study plants showing the most promise to be developed as anti-aging, anti-blemish and hair care products. MATERIALS AND METHODS: A literature analysis of plants of the IECIC list, present in French Polynesia was conducted. The most interesting plants from a cosmetic development standpoint were selected based on four main criteria, i.e. their traditional use in Polynesian cosmetic-related preparations, their biogeographical status, their phytochemistry of cosmetic interest, and lastly their availability and absence from the UICN list. Furthermore, a preliminary screening of antioxidant and anti-inflammatory activities was also performed on several extracts obtained. RESULTS: Eleven plants were chosen, and a compilation of multidisciplinary data emphasized each selected plant's potentiality. Traditional allegations showed uses ranging from dermatology such as wound healing or anti-inflammatory properties, to hair growth promoting preparations or even skin ligthening ones. Preliminary screenings were useful in narrowing the number of extracts to study. Literature-based data associated to traditional uses depicted how the remaining plants and plant parts could be developed for targeted cosmetic applications. CONCLUSIONS: A prospective approach of plants used traditionally for cosmetic purposes in French Polynesia gave insight on their development potential when paired with the appropriate multidisciplinary data. The eleven plants presented show promise in being developed sustainably as natural anti-aging or hair care products and as skin brightening agents.


Assuntos
Cosméticos , Preparações de Plantas/uso terapêutico , Plantas Medicinais , Envelhecimento/efeitos dos fármacos , Animais , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Polinésia , Preparações Clareadoras de Pele/uso terapêutico
5.
J Biochem Mol Toxicol ; 33(9): e22377, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332898

RESUMO

Hydroxytyrosol (HT), a primary phenolic antioxidant in olive oil, can afford protection from oxidative stress (OS) in different cells, including skin cells. In particular, it regulates several inflammation-associated processes as well as in improving the antioxidant defense system. However, there is no information about HT used in the treatment of hair loss. This work aimed at exploring the potential protective actions of HT against OS in rat dermal papilla cells. After treatment, the related expression of protein and messenger RNA were detected using morphological and molecular analyses. The results showed that HT significantly reduced intracellular reactive oxygen species level, apoptotic markers and inflammation induced by OS and enhanced cell survival by regulating autophagy. Furthermore, HT enhanced the secretion of hair growth factors in the anti-inflammation process. These results suggest that HT has a significant protective ability against OS and encourage the use of this biological ingredient as a possible tool to prevent alopecia.


Assuntos
Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Pele/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Álcool Feniletílico/farmacologia , Ratos , Pele/citologia
6.
Elife ; 82019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31343406

RESUMO

Skin vasculature cross-talking with hair follicle stem cells (HFSCs) is poorly understood. Skin vasculature undergoes dramatic remodeling during adult mouse hair cycle. Specifically, a horizontal plexus under the secondary hair germ (HPuHG) transiently neighbors the HFSC activation zone during the quiescence phase (telogen). Increased density of HPuHG can be induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1) in adult mice, and is accompanied by prolonged HFSC quiescence and by delayed entry and progression into the hair growth phase (anagen). Suggestively, skin vasculature produces BMP4, a well-established HFSC quiescence-inducing factor, thus contributing to a proliferation-inhibitory environment near the HFSC. Conversely, the HFSC activator Runx1 regulates secreted proteins with previously demonstrated roles in vasculature remodeling. We suggest a working model in which coordinated remodeling and molecular cross-talking of the adult epithelial and endothelial skin compartments modulate timing of HFSC activation from quiescence for proper tissue homeostasis of adult skin.


Assuntos
Diferenciação Celular , Folículo Piloso/fisiologia , Cabelo/crescimento & desenvolvimento , Fenômenos Fisiológicos da Pele , Células-Tronco/fisiologia , Remodelação Vascular , Animais , Homeostase , Camundongos
7.
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
8.
BMC Genomics ; 20(1): 512, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221080

RESUMO

BACKGROUND: Dermal papilla cells (DPCs), the "signaling center" of hair follicle (HF), delicately master continual growth of hair in mammals including cashmere, the fine fiber annually produced by secondary HF embedded in cashmere goat skins. Such unparalleled capacity bases on their exquisite character in instructing the cellular activity of hair-forming keratinocytes via secreting numerous molecular signals. Past studies suggested microRNA (miRNAs) and long non-coding RNAs (lncRNAs) play essential roles in a wide variety of biological process, including HF cycling. However, their roles and related molecular mechanisms in modulating DPCs secretory activities are still poorly understood. RESULTS: Here, we separately cultivated DPCs and their functionally and morphologically distinct dermal fibroblasts (DFs) from cashmere goat skins at anagen. With the advantage of high throughput RNA-seq, we synchronously identified 2540 lncRNAs and 536 miRNAs from two types of cellular samples at 4th passages. Compared with DFs, 1286 mRNAs, 18 lncRNAs, and 42 miRNAs were upregulated, while 1254 mRNAs, 53 lncRNAs and 44 miRNAs were downregulated in DPCs. Through overlapping with mice data, we ultimately defined 25 core signatures of DPCs, including HOXC8 and RSPO1, two crucial activators for hair follicle stem cells (HFSCs). Subsequently, we emphatically investigated the impacts of miRNAs and lncRNAs (cis- and trans- acting) on the genes, indicating that ncRNAs extensively exert negative and positive effects on their expressions. Furthermore, we screened lncRNAs acting as competing endogenous RNAs (ceRNAs) to sponge miRNAs and relief their repressive effects on targeted genes, and constructed related lncRNAs-miRNAs-HOXC8/RSPO1 interactive lines using bioinformatic tools. As a result, XR_310320.3-chi-miR-144-5p-HOXC8, XR_311077.2-novel_624-RSPO1 and others lines appeared, displaying that lncRNAs might serve as ceRNAs to indirectly adjust HFSCs status in hair growth. CONCLUSION: The present study provides an unprecedented inventory of lncRNAs, miRNAs and mRNAs in goat DPCs and DFs. We also exhibit some miRNAs and lncRNAs potentially participate in the modulation of HFSCs activation via delicately adjusting core signatures of DPCs. Our report shines new light on the latent roles and underlying molecular mechanisms of ncRNAs on hair growth.


Assuntos
Cabras/genética , Folículo Piloso/metabolismo , RNA Mensageiro/fisiologia , RNA não Traduzido/fisiologia , Animais , Derme/citologia , Feminino , Fibroblastos/metabolismo , Cabras/metabolismo , Cabelo/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Humanos , Camundongos , MicroRNAs/metabolismo , Pele/citologia , Trombospondinas/genética , Transcriptoma
9.
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
10.
Nat Commun ; 10(1): 2811, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243280

RESUMO

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.


Assuntos
Folículo Piloso/fisiologia , RNA de Cadeia Dupla/fisiologia , Regeneração/fisiologia , Receptor 3 Toll-Like/metabolismo , Tretinoína/metabolismo , Animais , Benzoatos/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Interleucina-6/administração & dosagem , Interleucina-6/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno , Estilbenos/farmacologia , Cicatrização
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.
Dermatol Ther ; 32(4): e12989, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31172647

RESUMO

Autologous rich plasma (PRP) is blood plasma with enhanced concentration of platelets and is enriched with several growth factors which stimulate tissue regeneration. The current study aimed to investigate the effect of PRP on hair regrowth in patients with alopecia areata (AA) totalis. Ten subjects (28.9 ± 6.28 years; five males and five females) with clinically diagnosed AA totalis for at least 3 years who had not received any treatment within 3 months prior to the study were recruited. Blood sample was collected in thrombocyte harvesting tubes. The PRP was separated via centrifugation. The patients' scalp was divided sagittally into two approximately equal parts. In each patient, 4 mL of PRP was injected intradermally into the left or right side of the scalp; in each point, 0.1 mL of PRP was injected. Each patient was followed up monthly for 4 months. No hair regrowth was seen in eight patients and in two patients only <10% hair regrowth was observed. Totally, no significant effect was found for PRP on hair regrowth (p > .05). There was no side effect during treatment. Single dermal PRP injection did not prove to have any effect on hair regrowth in these patients.


Assuntos
Alopecia em Áreas/terapia , Cabelo/crescimento & desenvolvimento , Plasma Rico em Plaquetas , Adolescente , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Couro Cabeludo/metabolismo , Resultado do Tratamento
13.
Arch Dermatol Res ; 311(8): 607-613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165933

RESUMO

Contact immunotherapy with diphenylcyclopropenone (DPCP) and anthralin is considered the treatment option for extensive alopecia areata (AA) unresponsive to DPCP immunotherapy alone. Only one study has described the efficacy of combination therapy; therefore, we investigated whether topical DPCP and anthralin can promote hair regrowth in DPCP-non responders. In this retrospective case-series we analyzed the efficacy and side effects of DPCP with anthralin in AA patients who did not respond to several months of treatment with DPCP alone. Thirty-two DPCP-nonresponsive AA patients were treated with DPCP and anthralin for the average of 8.3 ± 3.8 (3-17) months. During the treatment, 40.62% of patients (13 patients out of 32) had terminal hair regrowth. The mean of hair regrowth rate was 41%; it was mainly as partial hair regrowth (˂ 50%) and 27.27% of cases achieved > 50% terminal hair regrowth. Treatment response strongly related to the duration of combination therapy (p value ˂ 0.001), but we did not find any relation with other demographic characteristics. The first signs of response to treatment were noticed 2-12 months (5.5 ± 3.4) after initiation of combination therapy while there was a positive correlation among the duration of treatment and percentage of hair regrowth (p < 0.001). The most common complication was bullae (25%), and the least frequent side effect was generalized pruritus (3.1%). The combination therapy with DPCP and anthralin could be effective to treat DPCP non-responder AA patients. Additionally, the higher treatment response could be achieved by longer treatment duration.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Antralina/administração & dosagem , Ciclopropanos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Fatores Imunológicos/administração & dosagem , Administração Tópica , Adolescente , Adulto , Alopecia em Áreas/diagnóstico , Antralina/efeitos adversos , Criança , Ciclopropanos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prurido/induzido quimicamente , Prurido/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
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
15.
Cells ; 8(5)2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100937

RESUMO

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (ß-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).


Assuntos
Alopecia/terapia , Folículo Piloso/crescimento & desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Medicina Regenerativa/métodos , Transplante de Células-Tronco , Células-Tronco/metabolismo , Via de Sinalização Wnt , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adulto , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Humanos , Plasma Rico em Plaquetas , Engenharia Tecidual/métodos
16.
Genes (Basel) ; 10(5)2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035530

RESUMO

Each domestic dog breed is characterized by a strict set of physical and behavioral characteristics by which breed members are judged and rewarded in conformation shows. One defining feature of particular interest is the coat, which is comprised of either a double- or single-layer of hair. The top coat contains coarse guard hairs and a softer undercoat, similar to that observed in wolves and assumed to be the ancestral state. The undercoat is absent in single-coated breeds which is assumed to be the derived state. We leveraged single nucleotide polymorphism (SNP) array and whole genome sequence (WGS) data to perform genome-wide association studies (GWAS), identifying a locus on chromosome (CFA) 28 which is strongly associated with coat number. Using WGS data, we identified a locus of 18.4 kilobases containing 62 significant variants within the intron of a long noncoding ribonucleic acid (lncRNA) upstream of ADRB1. Multiple lines of evidence highlight the locus as a potential cis-regulatory module. Specifically, two variants are found at high frequency in single-coated dogs and are rare in wolves, and both are predicted to affect transcription factor (TF) binding. This report is among the first to exploit WGS data for both GWAS and variant mapping to identify a breed-defining trait.


Assuntos
Cromossomos/genética , Estudo de Associação Genômica Ampla , Cabelo/crescimento & desenvolvimento , Animais , Cruzamento , Mapeamento Cromossômico , Cães , Regulação da Expressão Gênica/genética , Cabelo/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Sequenciamento Completo do Genoma , Lobos/genética
17.
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
19.
Nat Commun ; 10(1): 1524, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30944305

RESUMO

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.


Assuntos
Cabelo/fisiologia , Macrófagos/fisiologia , Regeneração/fisiologia , Animais , Proteína Morfogenética Óssea 2 , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células , Quimiocinas/genética , Quimiocinas/metabolismo , Feminino , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Recombinantes , Pele/citologia , Pele/metabolismo , Células-Tronco , Estresse Mecânico , Fator de Crescimento Transformador beta
20.
Int J Mol Sci ; 20(8)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991711

RESUMO

Adiponectin (APN), released mainly from adipose tissue, is a well-known homeostatic factor for regulating glucose levels, lipid metabolism, and insulin sensitivity. A recent study showed that human hair follicles express APN receptors and the presence of APN-mediated hair growth signaling, thereby suggesting that APN is a potent hair growth-promoting adipokine. Previously, kojyl cinnamate ester derivatives (KCEDs) were synthesized in our institute as new anti-aging or adiponectin-/adipogenesis-inducing compounds. Here, we tested the activity of these derivatives to induce endogenous APN secretion. Among the derivatives, KCED-1 and KCED-2 showed improved activity in inducing APN mRNA expression, secretion of APN protein, and adipogenesis in human subcutaneous fat cells (hSCFs) when compared with the effects of Seletinoid G, a verified APN inducer. When human follicular dermal papilla cells were treated with the culture supernatant of KCED-1- or KCED-2-treated hSCFs, the mRNA expression of APN-induced hair growth factors such as insulin-like growth factor, hepatocyte growth factor, and vascular endothelial growth factor was upregulated compared with that in the control. Taken together, our study shows that among kojyl cinnamate ester derivatives, KCED-1, KCED-2, as well as Seletinoid G are effective inducers of endogenous APN production in subcutaneous fat tissues, which may in turn contribute to the promotion of hair growth in the human scalp.


Assuntos
Adiponectina/genética , Cinamatos/farmacologia , Folículo Piloso/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiponectina/metabolismo , Linhagem Celular , Cinamatos/química , Ésteres/química , Ésteres/farmacologia , Cabelo/citologia , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Cabelo/metabolismo , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
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