British Journal of Dermatology最新文献

{"title":"Human scalp hair follicles can \"taste\": Chemosensory signalling via the bitter taste receptor, TAS2R4, inhibits hair growth ex vivo.","authors":"Jennifer Gherardini, Thomas Rouillé, Rivka C Stone, Markus Fehrholz, Wolfgang Funk, Jose Rodríguez-Feliz, Alan J Bauman, Tamás Bíró, Jérémy Chéret, Ralf Paus","doi":"10.1093/bjd/ljaf060","DOIUrl":"https://doi.org/10.1093/bjd/ljaf060","url":null,"abstract":"<p><strong>Background: </strong>Taste receptors (TRs) exert many 'non-gustatory' chemosensory functions beyond the sensation of taste. Recently, human keratinocytes were found to express some bitter TRs, whose physiological functions remain unknown. Since we had discovered that human scalp hair follicles (HFs) use olfactory receptors to regulate their growth, we hypothesized that some bitter TRs may exert a similar function.</p><p><strong>Objectives: </strong>To explore whether human scalp HFs express the bitter TR, TAS2R4, whether its stimulation with cognate agonists or its selective knockdown impacts key human HF functions and, if yes, how.</p><p><strong>Methods: </strong>TAS2R4 mRNA and protein expression were assessed in situ, and organ-cultured scalp HFs were stimulated with the TAS2R4-agonistic natural sweetener, rebaudioside A (Reb A), in the presence/absence of TAS2R4 siRNA. Subsequently, changes in hair growth, growth factor expression, and HF gene expression were assessed ex vivo.</p><p><strong>Results: </strong>TAS2R4 mRNA and protein are mainly expressed in the outer root sheath and matrix of human anagen scalp HFs. Stimulating these with Reb-A ex vivo initially inhibits hair matrix keratinocyte proliferation, followed by enhanced intrafollicular production of catagen-promoting TGF-β2. This leads to TGF-β-driven premature catagen entry, which can be antagonized by TGF-β-neutralizing antibodies. Premature catagen induction is also seen with other known TAS2R4 agonists, while TAS2R4 knockdown in the presence of Reb-A promotes hair growth, thus documenting the TAS2R4-dependence of the observed HF effects of Reb-A. Gene expression profiling (RNA-seq) revealed differential transcriptional signatures consistent with TAS2R4-mediated changes in cell cycle control and TGF-β pathway signalling.</p><p><strong>Conclusion: </strong>Our study uncovers that human scalp HFs engage in chemosensation via bitter TRs to regulate their growth, matrix keratinocyte proliferation, growth factor production, and overall gene expression. Specifically, we demonstrate that a simple tastant like Reb-A can promote the anagen-catagen switch of human scalp HFs, their TGF-β2 production, and modulate both HF keratinocyte proliferation and intrafollicular gene transcription in a TAS2R4-dependent manner. This expands our understanding of bitter TR-mediated chemosensation in human skin and invites a novel, drug-free strategy for inhibiting unwanted hair growth (hirsutism, hypertrichosis) by targeting TAS2R4, e.g. via topical Reb-A.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of long scalp hair in humans.","authors":"Lo-Yu Chang, Maksim V Plikus, Nina G Jablonski, Sung-Jan Lin","doi":"10.1093/bjd/ljae456","DOIUrl":"10.1093/bjd/ljae456","url":null,"abstract":"<p><p>The ability to grow long scalp hair is a distinct human characteristic. It probably originally evolved to aid in cooling the sun-exposed head, although the genetic determinants of long hair are largely unknown. Despite ancestral variations in hair growth, long scalp hair is common to all extant human populations, which suggests its emergence before or concurrently with the emergence of anatomically modern humans (AMHs), approximately 300 000 years ago. Long scalp hair in AMHs was also a trait that was selected because it conveyed essential signals related to an individual's age, sexual maturity, health and social status. Biologically, hair length is primarily determined by the amount of time that a hair follicle spends in the active growth phase (anagen). While anagen duration is typically tightly regulated in most mammals, the inherent ability of a hair follicle to continuously recruit new dividing progenitors to its base, where hair fibre is generated, theoretically removes limits on maximal anagen duration. We propose a model wherein hair cycle progression into and out of anagen is regulated by evolutionary malleable molecular checkpoints. Several animal species and domesticated animal breeds display long body hair, which suggests that extremely long scalp hair in humans emerged via attenuation of an existing out-of-anagen checkpoint mechanism rather than via a newly evolved molecular programme. Studying congenital and somatic mosaicism conditions featuring altered hair length could potentially unveil the currently unknown molecular basis underlying this human trait.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"574-584"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitiligo is associated with lower body mass index: a retrospective case-control study.","authors":"Afsheen Sharifzadeh, Rachel Wetstone, Li-Chi Chen, Yurima Guilarte-Walker, Julie Flahive, John E Harris","doi":"10.1093/bjd/ljae478","DOIUrl":"10.1093/bjd/ljae478","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"753-755"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and patterns of newly developed pigmented lesions in adults at high risk for melanoma.","authors":"Anna K Wolber, Dilki Jayasinghe, Brigid Betz-Stablein, Monika Janda, H Peter Soyer, Harald Kittler","doi":"10.1093/bjd/ljae467","DOIUrl":"10.1093/bjd/ljae467","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"751-753"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating artificial intelligence into skin cancer pathways: the opportunities and obstacles.","authors":"Buket Beresford-Wylie, Samuel Ashcroft, Bindi Gaglani, Alice Green, Robert W Smillie, Katie Tucker, Ameet Bakhai, Ben Esdaile, Ioulios Palamaras","doi":"10.1093/bjd/ljae480","DOIUrl":"10.1093/bjd/ljae480","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"738-739"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimal important difference of pain numeric rating scale in patients with hidradenitis suppurativa: results from THESEUS.","authors":"Tim Pickles, John R Ingram","doi":"10.1093/bjd/ljae486","DOIUrl":"10.1093/bjd/ljae486","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"761-763"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical application of the Hedgehog inhibitor patidegib in patients with Gorlin syndrome: a phase II trial.","authors":"John T Lear, Catherine A Harwood, Zeeshaan Hasan, Jonathan Kentley, Jason Thomson, Andre Khoo, Alix Alderman, Mark DeSouza, Ervin H Epstein, Gerd G Kochendoerfer, Jean Y Tang","doi":"10.1093/bjd/ljae444","DOIUrl":"10.1093/bjd/ljae444","url":null,"abstract":"<p><strong>Background: </strong>Patients with Gorlin (basal cell naevus) syndrome (GS) have numerous phenotypic abnormalities due to overactivity of the hedgehog (HH) signalling pathway, most commonly caused by a heritable mutation in PTCH1, which encodes a major inhibitor of this pathway. Oral HH inhibitors (HHi) can reverse some of the manifestations, most prominent of which is the development of numerous cutaneous basal cell carcinomas (BCCs). In order to improve the benefit-risk ratio, we developed a gel containing a small cyclopamine-derived molecule that can be applied topically in expectation that this mode of delivery can reduce the burden of BCCs without producing the systemic adverse effects that cause patients to stop oral HHi treatment.</p><p><strong>Objectives: </strong>To determine whether or not patidegib topical gel 2% or 4% can accumulate in high enough concentrations to have local anti-BCC efficacy but not so high that systemic drug levels produce the adverse effects typical of oral HHi treatment.</p><p><strong>Methods: </strong>We conducted a small randomized double-blinded phase IIA trial at two sites in the UK, to assess the clinical and molecular efficacy and adverse effects of 6 months of twice-daily application of patidegib topical gel to the entire face, as well as to treatment-targeted surgically eligible BCCs at other anatomical sites.</p><p><strong>Results: </strong>Post hoc analyses suggested that patidegib topical gel reduced the number of new, surgically eligible BCCs and the level of HH signalling, with minimal adverse effects.</p><p><strong>Conclusions: </strong>Patidegib topical gel warrants further clinical development.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"611-617"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient preferences for the treatment of Bowen disease.","authors":"Shima Ahmady, Klara Mosterd, Maud H E Jansen, Nicole W J Kelleners-Smeets, Brigitte A B Essers","doi":"10.1093/bjd/ljae477","DOIUrl":"10.1093/bjd/ljae477","url":null,"abstract":"<p><strong>Background: </strong>Discrete choice experiments (DCEs) are increasingly used to understand and quantify patient preferences for a variety of treatments, services or screening in order to analyse the choices patients make when faced with different alternatives.</p><p><strong>Objectives: </strong>The aim of this DCE was to examine patient preferences for the treatment of Bowen disease.</p><p><strong>Methods: </strong>A DCE was conducted alongside a randomized controlled noninferiority trial comparing the effectiveness of surgical excision, methyl aminolaevulinate photodynamic therapy (MAL-PDT) and 5-fluorouracil (5-FU) cream as treatments for Bowen disease. Preferences were elicited by presenting patients with choice tasks between surgical excision, MAL-PDT and 5-FU cream with the following attributes: effectiveness, cosmetic outcome, side-effects, treatment duration and process. A mixed logit model was used to account for the panel nature of the data (repeated choices for each respondent) and heterogeneity in preference.</p><p><strong>Results: </strong>A total of 215 patients completed the DCE. Patients have a clear preference for excision and noninvasive therapies were less valued, as indicated by the large and negative label effect. Both moderate and good-to-excellent cosmetic outcomes were accepted and preferred to poor cosmetic outcomes for all treatments. In addition, none or mild-to-moderate side-effects were considered acceptable and preferred to severe side-effects.</p><p><strong>Conclusions: </strong>Patients show a clear preference for surgical excision, and of the two noninvasive treatments, 5-FU cream is preferred to MAL-PDT. Treatment choice is also determined by attributes such as effectiveness, cosmetic outcome and side-effects. In the context of shared decision making for Bowen disease, it is important to discuss the elements of treatment that patients value to ensure that an informed decision is made.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"653-659"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Behind the scenes' of a clinic appointment: insights from the patient experience of eczema.","authors":"Ria Patel","doi":"10.1093/bjd/ljae488","DOIUrl":"10.1093/bjd/ljae488","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"739-740"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin microbiome and polymorphous light eruption.","authors":"Vijaykumar Patra, Peter Wolf","doi":"10.1093/bjd/ljae513","DOIUrl":"10.1093/bjd/ljae513","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"569-570"},"PeriodicalIF":11.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}