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1.
Cell ; 169(6): 1119-1129.e11, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28552347

RESUMO

The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.


Assuntos
Folículo Piloso/citologia , Células-Tronco/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Células Epiteliais/metabolismo , Folículo Piloso/metabolismo , Humanos , Inflamação/metabolismo , Proteína Jagged-1/metabolismo , Camundongos
2.
PLoS Genet ; 19(2): e1010614, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36745673

RESUMO

Enhancers are context-specific regulators of expression that drive biological complexity and variation through the redeployment of conserved genes. An example of this is the enhancer-mediated control of Engrailed 1 (EN1), a pleiotropic gene whose expression is required for the formation of mammalian eccrine sweat glands. We previously identified the En1 candidate enhancer (ECE) 18 cis-regulatory element that has been highly and repeatedly derived on the human lineage to potentiate ectodermal EN1 and induce our species' uniquely high eccrine gland density. Intriguingly, ECE18 quantitative activity is negligible outside of primates and ECE18 is not required for En1 regulation and eccrine gland formation in mice, raising the possibility that distinct enhancers have evolved to modulate the same trait. Here we report the identification of the ECE20 enhancer and show it has conserved functionality in mouse and human developing skin ectoderm. Unlike ECE18, knock-out of ECE20 in mice reduces ectodermal En1 and eccrine gland number. Notably, we find ECE20, but not ECE18, is also required for En1 expression in the embryonic mouse brain, demonstrating that ECE20 is a pleiotropic En1 enhancer. Finally, that ECE18 deletion does not potentiate the eccrine phenotype of ECE20 knock-out mice supports the secondary incorporation of ECE18 into the regulation of this trait in primates. Our findings reveal that the mammalian En1 regulatory machinery diversified to incorporate both shared and lineage-restricted enhancers to regulate the same phenotype, and also have implications for understanding the forces that shape the robustness and evolvability of developmental traits.


Assuntos
Genes Homeobox , Proteínas de Homeodomínio , Camundongos , Animais , Humanos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Sequências Reguladoras de Ácido Nucleico , Camundongos Knockout , Fenótipo , Glândulas Sudoríparas/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
3.
J Am Acad Dermatol ; 90(6): 1182-1189, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38341148

RESUMO

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.


Assuntos
Alopecia , Consenso , Técnica Delphi , Humanos , Alopecia/terapia , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Cicatriz/terapia , Cicatriz/etiologia , Dermatologistas
4.
J Am Acad Dermatol ; 84(6): 1594-1601, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32926985

RESUMO

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.


Assuntos
Alopecia em Áreas/diagnóstico , Consenso , Dermatologia/normas , Carga Global da Doença , Alopecia em Áreas/epidemiologia , Alopecia em Áreas/etiologia , Alopecia em Áreas/terapia , Comorbidade , Técnica Delphi , Dermatologia/métodos , Dermoscopia , Folículo Piloso/diagnóstico por imagem , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/patologia , Humanos , Cooperação Internacional , Guias de Prática Clínica como Assunto , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
7.
J Am Acad Dermatol ; 83(1): 123-130, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32165196

RESUMO

BACKGROUND: A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. OBJECTIVE: To produce an international consensus statement on the use and utility of various treatments for AA. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. RESULTS: In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. LIMITATIONS: The study included a comprehensive list of systemic treatments for AA but not all treatments used. CONCLUSION: Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.


Assuntos
Alopecia em Áreas/terapia , Administração Oral , Administração Tópica , Corticosteroides/uso terapêutico , Fatores Etários , Alopecia em Áreas/tratamento farmacológico , Terapia Combinada , Terapias Complementares , Técnica Delphi , Fármacos Dermatológicos/uso terapêutico , Prova Pericial , Humanos , Injeções Intralesionais , Fototerapia , Índice de Gravidade de Doença , Resultado do Tratamento
8.
J Am Acad Dermatol ; 81(5): 1093-1098, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30502417

RESUMO

BACKGROUND: The Dermatology Foundation (DF) has a comprehensive career development award (CDA) program. OBJECTIVE: To assess the impact of this program, a cross-sectional survey of recipients receiving support between 1990 and 2012 was performed. METHODS: Award recipients completed a questionnaire concerning their career status and record of research funding. To verify the self-reported funding data, information about each awardee was extracted from the National Institutes of Health Research Portfolio Online Reporting Tools database and used to define funding acquired by CDA recipients. RESULTS: In all, 84% of CDA recipients responded to the survey. A total of 213 awardees (79%) hold full- or part-time positions in academic medicine. Approximately 70% of the award recipients in academic medicine have received federal research funding. The National Institutes of Health Research Portfolio Online Reporting Tools database and other sources indicated that the funding acquired by CDA recipients through 2015 and 2017 amounted to approximately $365.4 million and $451.8 million, respectively. Each dollar of DF CDA funding through 2015 (ie, $36.2 million) was linked to more than $10 in grant support through 2015 and $12 through 2017. LIMITATIONS: This cross-sectional survey was retrospective and (in part) self-reported. CONCLUSIONS: The DF has succeeded in supporting the career development of basic, translational, and clinical investigators and fostered the promotion and retention of these individuals in academic medicine.


Assuntos
Distinções e Prêmios , Pesquisa Biomédica/economia , Dermatologia , Fundações , Adulto , Estudos Transversais , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Autorrelato , Estados Unidos
9.
J Am Acad Dermatol ; 79(3): 470-478.e3, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29128463

RESUMO

BACKGROUND: Although alopecia areata is a common disorder, it has no US Food and Drug Administration-approved treatment and evidence-based therapeutic data are lacking. OBJECTIVE: To develop guidelines for the diagnosis, evaluation, assessment, response criteria, and end points for alopecia areata. METHODS: Literature review and expert opinion of a group of dermatologists specializing in hair disorders. RESULTS: Standardized methods of assessing and tracking hair loss and growth, including new scoring techniques, response criteria, and end points in alopecia areata are presented. LIMITATIONS: The additional time to perform the assessments is the primary limitation to use of the methodology in clinical practice. CONCLUSION: Use of these measures will facilitate collection of standardized outcome data on therapeutic agents used in alopecia areata both in clinical practice and in clinical trials.


Assuntos
Alopecia em Áreas/diagnóstico , Cabelo/crescimento & desenvolvimento , Avaliação de Resultados em Cuidados de Saúde/métodos , Guias de Prática Clínica como Assunto , Alopecia em Áreas/tratamento farmacológico , Coleta de Dados , Autoavaliação Diagnóstica , Determinação de Ponto Final , Humanos , Índice de Gravidade de Doença
11.
Lab Invest ; 96(1): 81-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26707825

RESUMO

TR3 is an orphan member of the steroid/thyroid/retinoid nuclear receptor superfamily of transcription factors and it plays a pivotal role in regulating cell growth and apoptosis. The expression and function of TR3 in skin have not been well investigated. Using a cDNA expression assay, we discover that TR3 is significantly enriched in human telogen bulge compared with anagen bulb. Immunohistochemical staining confirms that TR3 is highly expressed in the bulge region of human hair follicles and it colocalizes with cytokeratin 15 (K15), an epithelial stem cell marker. To study the function of TR3 in the effect of androgens in keratinocytes, we treat HaCaT keratinocytes and primary human keratinocytes with dihydrotestosterone (DHT) and testosterone (T). The treated keratinocytes show a dose-dependent growth reduction to DHT and T. DHT increases the expression of TR3 in keratinocytes, associated with a concomitant increase of BAD and decrease of Bcl-2 expression. Knockdown TR3 expression by siRNA blocks the inhibitory effect of DHT on keratinocyte proliferation. Our results demonstrate that TR3 is localized to the stem cell compartment in the human hair follicles. Androgen increases TR3 expression in cultured keratinocytes. Our data suggest that TR3 mediates at least part of the inhibitory effect of androgens on keratinocytes.


Assuntos
Folículo Piloso/citologia , Queratinócitos/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Células-Tronco/metabolismo , Linhagem Celular , Di-Hidrotestosterona/farmacologia , Técnicas de Silenciamento de Genes , Folículo Piloso/química , Folículo Piloso/metabolismo , Humanos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Testosterona/farmacologia , Regulação para Cima/efeitos dos fármacos
13.
Semin Cell Dev Biol ; 23(9): 946-53, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23085626

RESUMO

Activation of epithelial stem cells and efficient recruitment of their proliferating progeny plays a critical role in cutaneous wound healing. The reepithelialized wound epidermis has a mosaic composition consisting of progeny that can be traced back both to epidermal and several types of hair follicle stem cells. The contribution of hair follicle stem cells to wound epidermis is particularly intriguing as it involves lineage identity change from follicular to epidermal. Studies from our laboratory show that hair follicle-fated bulge stem cells commit only transient amplifying epidermal progeny that participate in the initial wound re-epithelialization, but eventually are outcompeted by other epidermal clones and largely disappear after a few months. Conversely, recently described stem cell populations residing in the isthmus portion of hair follicle contribute long-lasting progeny toward wound epidermis and, arguably, give rise to new interfollicular epidermal stem cells. The role of epithelial stem cells during wound healing is not limited to regenerating stratified epidermis. By studying regenerative response in large cutaneous wounds, our laboratory uncovered that epithelial cells in the center of the wound can acquire greater morphogenetic plasticity and, together with the underlying wound dermis, can engage in an embryonic-like process of hair follicle neogenesis. Future studies should uncover the cellular and signaling basis of this remarkable adult wound regeneration phenomenon.


Assuntos
Células Epidérmicas , Células Epiteliais/citologia , Folículo Piloso/citologia , Reepitelização/fisiologia , Regeneração/fisiologia , Glândulas Sebáceas/citologia , Células-Tronco/citologia , Adulto , Medula Óssea/fisiologia , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Cicatriz/prevenção & controle , Epiderme/lesões , Epiderme/fisiologia , Células Epiteliais/fisiologia , Folículo Piloso/fisiologia , Humanos , Glândulas Sebáceas/fisiologia , Células-Tronco/fisiologia , Ferimentos Penetrantes/patologia , Ferimentos Penetrantes/reabilitação
14.
Adv Healthc Mater ; 13(12): e2303256, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38207170

RESUMO

Janus kinase (JAK) inhibitors are approved for many dermatologic disorders, but their use is limited by systemic toxicities including serious cardiovascular events and malignancy. To overcome these limitations, injectable hydrogels are engineered for the local and sustained delivery of baricitinib, a representative JAK inhibitor. Hydrogels are formed via disulfide crosslinking of thiolated hyaluronic acid macromers. Dynamic thioimidate bonds are introduced between the thiolated hyaluronic acid and nitrile-containing baricitinib for drug tethering, which is confirmed with 1H and 13C nuclear magnetic resonance (NMR). Release of baricitinib is tunable over six weeks in vitro and active in inhibiting JAK signaling in a cell line containing a luciferase reporter reflecting interferon signaling. For in vivo activity, baricitinib hydrogels or controls are injected intradermally into an imiquimod-induced mouse model of psoriasis. Imiquimod increases epidermal thickness in mice, which is unaffected when treated with baricitinib or hydrogel alone. Treatment with baricitinib hydrogels suppresses the increased epidermal thickness in mice treated with imiquimod, suggesting that the sustained and local release of baricitinib is important for a therapeutic outcome. This study is the first to utilize a thioimidate chemistry to deliver JAK inhibitors to the skin through injectable hydrogels, which has translational potential for treating inflammatory disorders.


Assuntos
Azetidinas , Hidrogéis , Purinas , Pirazóis , Pele , Sulfonamidas , Animais , Hidrogéis/química , Purinas/química , Purinas/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/administração & dosagem , Camundongos , Pirazóis/química , Pirazóis/farmacologia , Azetidinas/química , Azetidinas/farmacologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Humanos , Psoríase/tratamento farmacológico , Psoríase/patologia , Psoríase/induzido quimicamente , Imiquimode/química , Imiquimode/farmacologia , Inibidores de Janus Quinases/química , Inibidores de Janus Quinases/farmacologia , Feminino
15.
JAMA Dermatol ; 160(3): 341-350, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324292

RESUMO

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.


Assuntos
Alopecia em Áreas , Humanos , Alopecia/diagnóstico , Alopecia em Áreas/diagnóstico , Consenso , Morbidade , Qualidade de Vida
16.
Mol Carcinog ; 52(10): 751-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22431489

RESUMO

The multistage model of nonmelanoma skin carcinogenesis has contributed significantly to our understanding of epithelial cancer in general. We used the Krt1-15CrePR1;R26R transgenic mouse to determine the contribution of keratin 15+ cells from the hair follicle to skin tumor development by following the labeled progeny of the keratin 15 expressing cells into papillomas. We present three novel observations. First, we found that keratin 15 expressing cells contribute to most of the papillomas by 20 weeks of promotion. Second, in contrast to the transient behavior of labeled keratin 15-derived progeny in skin wound healing, keratin 15 progeny persist in papillomas, and some malignancies for many months following transient induction of the reporter gene. Third, papillomas have surprising heterogeneity not only in their cellular composition, but also in their expression of the codon 61 signature Ha-ras mutation with approximately 30% of keratin 15-derived regions expressing the mutation. Together, these results demonstrate that keratin 15 expressing cells of the hair follicle contribute to cutaneous papillomas with long term persistence and a subset of which express the Ha-ras signature mutation characteristic of initiated cells.


Assuntos
Transformação Celular Neoplásica/patologia , Folículo Piloso/patologia , Queratina-15/fisiologia , Papiloma/patologia , Neoplasias Cutâneas/patologia , Células-Tronco/patologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Carcinógenos/toxicidade , Transformação Celular Neoplásica/efeitos dos fármacos , Feminino , Genes ras/genética , Folículo Piloso/efeitos dos fármacos , Humanos , Integrases/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Microdissecção e Captura a Laser , Camundongos , Camundongos Transgênicos , Mutação/genética , Papiloma/induzido quimicamente , Papiloma/genética , Pele/efeitos dos fármacos , Pele/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Células-Tronco/efeitos dos fármacos , Acetato de Tetradecanoilforbol/toxicidade
17.
Nature ; 447(7142): 316-20, 2007 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-17507982

RESUMO

The mammalian hair follicle is a complex 'mini-organ' thought to form only during development; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders.


Assuntos
Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Regeneração/fisiologia , Proteínas Wnt/metabolismo , Cicatrização/fisiologia , Animais , Linhagem da Célula , Células Epiteliais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologia , Ferimentos e Lesões/patologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-36123030

RESUMO

Adult mammals retain the remarkable ability to regenerate hair follicles after wounding. Wound-induced hair neogenesis (WIHN) in many ways recapitulates embryogenesis. The origin of the stem cells that give rise to a nascent hair follicle after wounding and the role of mesenchymal cells and signaling pathways responsible for this regenerative phenomenon are slowly being elucidated. WIHN provides a potential therapeutic window for manipulating cell fate by the introduction of factors during the wound healing process to enhance hair follicle formation.


Assuntos
Cabelo , Pele , Animais , Humanos , Pele/metabolismo , Cicatrização , Folículo Piloso , Alopecia/metabolismo , Mamíferos
19.
JAMA Dermatol ; 159(2): 143-150, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36515962

RESUMO

Importance: Clinical estimation of hair density has an important role in assessing and tracking the severity and progression of alopecia, yet to the authors' knowledge, no automation currently exists for this process. While some algorithms have been developed to assess alopecia presence on a binary level, their scope has been limited by focusing on a re-creation of the Severity of Alopecia Tool (SALT) score for alopecia areata (AA). Yet hair density loss is common to all alopecia forms, and an evaluation of that loss is used in established scoring systems for androgenetic alopecia (AGA), central centrifugal cicatricial alopecia (CCCA), and many more. Objective: To develop and validate a new model, HairComb, to automatically compute the percentage hair loss from images regardless of alopecia subtype. Design, Setting, and Participants: In this research study to create a new algorithmic quantification system for all hair loss, computational imaging analysis and algorithm design using retrospective image data collection were performed. This was a multicenter study, where images were collected at the Children's Hospital of Philadelphia, University of Pennsylvania (Penn), and via a Penn Dermatology web interface. Images were collected from 2015 to 2021, and they were analyzed from 2019 to 2021. Main Outcomes and Measures: Scoring systems correlation analysis was measured by linear and logarithmic regressions. Algorithm performance was evaluated using image segmentation accuracy, density probability regression error, and average percentage hair loss error for labeled images, and Pearson correlation for manual scores. Results: There were 404 participants aged 2 years and older that were used for designing and validating HairComb. Scoring systems correlation analysis was performed for 250 participants (70.4% female; mean age, 35.3 years): 75 AGA, 66 AA, 50 CCCA, 27 other alopecia diagnoses (frontal fibrosing alopecia, lichen planopilaris, telogen effluvium, etc), and 32 unaffected scalps without alopecia. Scoring systems showed strong correlations with underlying percentage hair loss, with coefficient of determination R2 values of 0.793 and 0.804 with respect to log of percentage hair loss. Using HairComb, 92% accuracy, 5% regression error, 7% hair loss difference, and predicted scores with errors comparable to annotators were achieved. Conclusions and Relevance: In this research study,it is shown that an algorithm quantitating percentage hair loss may be applied to all forms of alopecia. A generalizable automated assessment of hair loss would provide a way to standardize measurements of hair loss across a range of conditions.


Assuntos
Alopecia em Áreas , Alopecia , Criança , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Alopecia/diagnóstico , Alopecia em Áreas/diagnóstico , Cabelo , Couro Cabeludo
20.
J Invest Dermatol ; 143(11): 2132-2144.e15, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37236597

RESUMO

Skin injury and several diseases elicit fibrosis and induce hair follicle (HF) growth arrest and loss. The resulting alopecia and disfiguration represent a severe burden for patients, both physically and psychologically. Reduction of profibrotic factors such as dipeptidyl peptidase 4 (DPP4) might be a strategy to tackle this issue. We show DPP4 overrepresentation in settings with HF growth arrest (telogen), HF loss, and nonregenerative wound areas in mouse skin and human scalp. Topical DPP4 inhibition with Food and Drug Administration/European Medicines Agency-approved sitagliptin on preclinical models of murine HF activation/regeneration results in accelerated anagen progress, whereas treatment of wounds with sitagliptin results in reduced expression of fibrosis markers, increased induction of anagen around wounds, and HF regeneration in the wound center. These effects are associated with higher expression of Wnt target Lef1, known to be required for HF anagen/HF-activation and regeneration. Sitagliptin treatment decreases profibrotic signaling in the skin, induces a differentiation trajectory of HF cells, and activates Wnt targets related to HF activation/growth but not those supporting fibrosis. Taken together, our study shows a role for DPP4 in HF biology and shows how DPP4 inhibition, currently used as oral medication to treat diabetes, could be repurposed into a topical treatment agent to potentially reverse HF loss in alopecia and after injury.

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