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Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, −7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects. [Display omitted] • These hybrid vesicles improved storage stability for cargos, follicle retention, and drug encapsulation efficiency (EE%) for finasteride. • The Hybrid/Au@Fi (115.07 ± 0.32 nm, −7.50 ± 1.68 mV) facilitated simulated in vitro layered dermal papilla cell (DPC) migration and angiogenesis with favorable cell dynamic behavior and no cytotoxicity. • In an AGA mouse model, once-daily topical application of Hybrid/Au@Fi gel exhibited a faster transition of hair follicles from the catagen to the anagen, higher hair regrowth coverage, and improved quality of regrowth hair, compared to once-daily 5% minoxidil treatment. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA), an immune-mediated disorder, is marked by temporary, nonscarring hair loss. The bulge area is protected from immune attacks by immune privilege; however, recent studies demonstrated immune cells infiltrating the bulge area. Objective: This study aims to investigate the immunohistochemical expression of the sex-determining region Y-box 9 (SOX9) and cluster of differentiation 34 (CD34) in AA patients as markers of hair follicle stem cells (HFSCs) and progenitor cells, respectively. Methods: Immunohistochemical staining of SOX9 and CD34 was applied on skin samples of 20 AA patients and 20 healthy controls. Results: SOX9 and CD34 were significantly lower in lesional samples of cases compared to perilesional and control skin biopsies. Furthermore, SOX9 level was negatively correlated with the severity of alopecia tool score (SALT score) among the studied AA patients. Moreover, lowered SOX9 expression was present in patients with recurrent attacks. Conclusions: The significant reduction of stem cell markers (SOX9 and CD34) in our studied AA cases signifies the pathological affection of HFSCs and their progeny in AA. This is thought to cause a loss of competence in generating new hair in some AA cases, which needs to be validated in further research. Limitations of the study: This study has a small sample size. [ABSTRACT FROM AUTHOR]

The human skin is a readily accessibl esurface for drug delivery. Skin of an average adult body covers a surface of approximately 2m2 and receives about one-third of the blood circulating through the body. Over the past decades, developing controlled drug delivery as become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on anaverage, 10-70 hair follicles and 200-250 sweat ducts on every square centimeters of the skin area. It is one of the most readily accessibl eorgans of the human body. There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, thes kin, in particular the stratum corneum, poses a formid able barrier drug penetration there by limiting topical and Transdermal bioavailability. Skin penetration enhancement techniques have been devel oped to improve bioavailability and increase the range of drugs for which topical and Transdermal delivery syste(NDDS). [ABSTRACT FROM AUTHOR]

The hair follicle and nail unit develop and regenerate through epithelial-mesenchymal interactions. Here, we review some of the key signals and molecular interactions that regulate mammalian hair follicle and nail formation during embryonic development and how these interactions are reutilized to promote their regeneration during adult homeostasis and in response to skin wounding. Finally, we highlight the role of some of these signals in mediating human hair follicle and nail conditions. [Display omitted] • Reciprocal signaling between different cell types regulates hair follicle development. • Hair follicle regeneration after injury uses developmental and wound repair processes. • Reciprocal signaling spatiotemporally regulates adult hair follicle regeneration. • Nails share similar developmental mechanisms as hair follicles. • Mutations in genes involved in hair and nail development lead to diseases in humans. [ABSTRACT FROM AUTHOR]

While many gene expression studies have focused on male pattern baldness (MPB), few studies have investigated the genetic differences between bald and non-bald hair follicles in female pattern hair loss (FPHL). This study aimed to identify molecular biomarkers associated with FPHL through genetic analysis of paired bald and non-bald hair follicles from 18 FPHL patients, using next-generation sequencing (NGS) techniques. RNA transcriptome analysis was performed to identify differentially expressed genes (DEGs) between bald and non-bald hair follicles in FPHL. The DEGs were validated using real-time PCR, and protein expression was confirmed through immunohistochemistry and western blot analysis. Our findings suggest that HOXB13, SFRP2, PTGDS, CXCR3, SFRP4, SOD3, and DCN are significantly upregulated in bald hair follicles compared to non-bald hair follicles in FPHL. SFRP2 and PTGDS were found to be consistently highly expressed in bald hair follicles in all 18 samples. Additionally, elevated protein levels of SFRP2 and PTGDS were confirmed through western blot and immunohistochemical analysis. Our study identified SFRP2 and PTGDS as potential biomarkers for FPHL and suggests that they may play a role in inducing hair loss in this condition. These findings provide a foundation for further research on the pathogenesis of FPHL and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Demodex density is known to increase in various immunosuppressive conditions. The relationship between biologic therapy and Demodex density remains unknown. We aimed to investigate whether the density of Demodex mites is higher in psoriasis patients treated with biologic agents compared to treatment‐naive or topically treated patients. Methods: A cross‐sectional study was conducted, comparing psoriasis patients receiving biologic therapy (n = 34) with controls (n = 33). Demodex density was assessed using the standardized skin surface biopsy technique (SSSB). Statistical analysis was performed to compare the densities and prevalence of demodicosis between the two groups. Results: Demodex density was significantly higher in the biologic therapy group compared to the control group on the right cheek (7.29 vs. 0.12/cm2; P = 0.001), left cheek (8.15 vs. 0.24/cm2; P = 0.002), and whole face (average of all four regions: 5.50 vs. 0.80/cm2; P = 0.001). The prevalence of demodicosis was significantly higher in the biologic therapy group on the forehead (35.3% vs. 12.1%; P = 0.043), right cheek (41.2% vs. 0%; P < 0.001), and left cheek (44.1% vs. 0%; P < 0.001). The frequency of cases with demodicosis in at least one localization was higher in the biological therapy group compared to the control group (61.8% vs. 15.2%; P < 0.001). Conclusions: Psoriasis patients receiving biologic therapy had a higher Demodex density and prevalence of demodicosis compared to controls. Biologics may lead to an increase in Demodex density by blocking specific cytokines, such as interleukin‐17 and tumor necrosis factor‐α, which play a role in immunity against Demodex. Further research is needed to explore the impact of different biological agents on Demodex density. Plain Language Summary: "Demodex" mites live in human hair follicles, usually without causing any harm. However, when the immune system is suppressed due to several conditions, the Demodex density (Dd) can increase. "Biological drugs" that suppress some immunity elements are used to treat psoriasis. We aimed to determine if Dd increases in 34 psoriasis patients using biological therapies compared to those who do not. Dd on the face was significantly higher in the biological treatment group compared to the controls. The blockage of certain immune system molecules by biological drugs could explain this. [ABSTRACT FROM AUTHOR]

Therapeutic antibodies (Abs) have been anticipated as promising alternatives to conventional treatments such as topical minoxidil and oral finasteride for androgenetic alopecia (AGA). Due to the high molecular weight of typical Abs, the half-life of subcutaneous Abs exceeds 2 weeks, allowing an administration intervals of once a month or longer. Direct injection into the areas of hair loss is also feasible, potentially enhancing treatment efficacy while minimizing systemic side effects. However, therapeutic Abs are rarely developed for AGA therapy due to the requirement to be responsiveness to androgens and to exist in the extracellular fluid or cell surface surrounding the hair follicle. In this review, we introduce recent progress of antibody therapeutics in AGA targeting the prolactin receptor, Interleukin-6 receptor, C-X-C motif chemokine ligand 12, and dickkopf 1. As therapeutic Abs for AGA are still in the early stages, targets need further validation and optimization for clinical application. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Keratosis pilaris (KP) is a prevalent benign dermatological condition characterized by small bumps at the hair follicles alongside surrounding redness, significantly impacting both aesthetics and mental well‐being.This study investigated the potential benefits of a non‐cross‐linked hyaluronic acid (HA) compound for treating KP.A split‐body, investigator‐blinded, randomized, intraindividual comparative clinical trial was conducted. The non‐cross‐linked HA compound was injected into KP‐affected regions on both upper arms. The treatment was delivered across four sessions scheduled at 4‐week intervals. Blinded physicians and patients assessed differences in erythema, skin roughness, and overall scores between treated and control areas at the final follow‐up visit. At the 12th and 24th weeks post‐treatment, a four‐point scale was utilized to assess subjects' perceived treatment efficacy. Additionally, dermoscopic images, histological alterations, and adverse events were monitored.Physician assessments revealed a significant reduction in roughness and overall scores for treated areas compared to controls. Patient self‐assessments also reflected improvements in roughness, redness, and overall scores for treated sides at the final visit, with 35.71% of patients demonstrating sustained improvement in redness and 71.43% reporting persistent improvements in roughness at 24th weeks post‐treatment. The dermatoscopic examinations revealed a notable enhancement in both the quantity of follicular plugs and the extent of erythema among the subjects in the treatment group. Histopathological outcomes also demonstrated improvement.This study suggests that the non‐cross‐linked HA compound effectively improves skin roughness and promotes hair shaft growth in KP treatment, demonstrating a favorable safety profile. These findings position it as a potentially viable alternative therapy in clinical practice. [ABSTRACT FROM AUTHOR]

Background Objectives Materials and Methods Results Conclusion There is still no certain effective treatment for vitiligo as a common chronic skin disorder characterized by depigmented patches and loss of skin melanocytes.This study evaluates the efficacy of oral silymarin combined with hair follicle transplantation compared to follicle transplantation alone in the treatment of refractory vitiligo.Twenty refractory vitiligo patients were enrolled in this randomized controlled clinical trial, following up for 3 months. One group underwent hair transplantation plus oral silymarin, while the other group underwent follicle transplantation alone. We assessed the progress with Vitiligo Extent Tensity Index (VETI) in both groups and the peri‐follicular pigmentation diameter was estimated monthly. The Friedman test for comparing two groups at the end and the Mann–Whitney test for comparing two groups during each month was used.The mean age was 30.22 (18–59) years, with the male to female ratio of 1:1. The decrease in the VETI and increase in the perifollicular pigmentation was statistically significant between silymarin and another group in monthly follow‐up (p‐value: 0.019, 0.019, and 0.035, respectively). Finally, the re‐pigmentation was notable in silymarin group (p‐value <0.001 vs. 0.029, respectively). In addition, both genders had a significant increase in peri‐follicular re‐pigmentation in the last follow‐up (p‐value: 0.012 and 0.044, respectively); although the improvement was not statistically significant between genders in each month.According to our study, silymarin in combination with hair transplantation could be a potential medical treatment for vitiligo; however, further trials are needed to establish the efficacy of combination therapies. [ABSTRACT FROM AUTHOR]

Background: The probiotic potential of Lacticacid bacteria has been studied in various medical complications, from gastrointestinal diseases to antibiotic resistance infections recently. Moreover, diabetic ulcer (DU) is known as one of the most significant global healthcare concerns, which comprehensively impacts the quality of life for these patients. Given that the conventional treatments of DUs have failed to prevent later complications completely, developing alternative therapies seems to be crucial. Methods: We designed the stable oleogel-based formulation of viable probiotic cells, including Lactobacillus rhamnosus (L. rhamnosus), Lactobacillus casei (L. casei), Lactobacillus fermentum (L. fermentum), and Lactobacillus acidophilus (L. acidophilus) individually to investigate their effect on wound healing process as an in vivo study. The wound repair process was closely monitored regarding morphology, biochemical, and histopathological changes over two weeks and compared it with the effects of topical tetracycline as an antibiotic approach. Furthermore, the antibiofilm activity of probiotic bacteria was assessed against some common pathogens. Results: The findings indicated that all tested lactobacillus groups (excluded L. casei) included in the oleogel-based formulation revealed a high potential for repairing damaged skin due to the considerably more levels of hydroxyproline content of tissue samples along with the higher numerical density of mature fibroblasts cell and volume density of hair follicles, collagen fibrils, and neovascularization in comparison with antibiotic and control groups. L. acidophilus and L. rhamnosus showed the best potential of wound healing among all lactobacillus species, groups treated by tetracycline and control groups. Besides, L. rhamnosus showed a significant biofilm inhibition activity against tested pathogens. Conclusions: This experiment demonstrated that the designed formulations containing probiotics, particularly L. acidophilus and L. rhamnosus, play a central role in manipulating diabetic wound healing. It could be suggested as an encouraging nominee for diabetic wound-healing alternative approaches, though further studies in detailed clinical trials are needed. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Achieving successful outcomes in hair transplant surgery involves various critical factors, including donor area harvesting, graft survival, and minimizing post‐operative complications. This study investigates the differences in grafts obtained using the rotary and oscillatory punch methods during follicular unit extraction (FUE) surgery.The study involved 15 patients undergoing FUE. Four 4 × 6 cm2 areas in two rows were selected for each patient, with each row utilizing a different punch method (rotary or oscillatory). The grafts were extracted and examined under a microscope, classified into single, double single, double, and triple categories. The total yield rate and average number of hairs per graft were measured and compared.The average number of hair follicles per graft was 2.029 for the rotary method and 2.084 for the oscillatory method, indicating no statistically significant difference. However, the total yield rate was 88.3% for the rotary group and 90.5% for the oscillatory group, with the difference being statistically significant. In selected cases with soft scalps or deeper punch requirements, the oscillatory method showed significantly better results, with an average of 2.078 hairs per graft compared to 1.836 for the rotary method. The total yield rate in these cases was 91% for oscillatory and 86% for rotary.While the overall differences between rotary and oscillatory punches are minimal, the oscillatory punch is significantly more effective in cases with soft scalps or deeper punch requirements. Adhering to a structured guideline before extraction can help reduce the transection rate and increase the number of hairs per graft. [ABSTRACT FROM AUTHOR]

Background: Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia characterized by an irreversible destruction of the hair follicle resulting in its permeant destruction. The clinical presentation of LPP is a progressive patchy scarring alopecia. A variety of systemic agents is used to treat LPP with varying success. The aim of this retrospective, real-life analysis was to evaluate the treatment of hydroxychloroquine for LPP. Method: In this retrospective, single-center study, we analyzed 110 patients with LPP and frontal fibrosing alopecia (FFA) who received treatment over a 12-month period from March 2014 to March 2021 at the Department of Dermatology, University of Mainz Medical Center. Patient records were analyzed for response to treatment, co-morbidities, disease progression-free survival (DPFS), and safety. Clinical parameters associated with treatment response were determined with Cox regression modelling and logistic regression. Results: Overall, 77 of 110 patients were treated with a systemic agent. There was a clear association between LPP and the occurrence of Hashimoto thyroiditis. Topical treatment with corticosteroids did not improve clinical symptoms in the majority of patients (15 out of 101). In 71% of patients treated with systemic cyclosporine A and 62% of patients treated with hydroxychloroquine, we observed a significant resolution of the inflammatory process, which correlated with a robust durable clinical response (p < 0.001). Toxicity was observed in 17% (n = 9) of patients receiving systemic treatment with hydroxychloroquine and correlated with the duration of systemic treatment (p < 0.001). Treatment discontinuation was associated with a flare-up of clinical symptoms (29%), which required the re-initiation of second-line therapy in 13 out of 51 patients. Overall, the initiation of second-line treatment, either hydroxychloroquine or Cyclosporine A (CsA), yielded positive results, especially in the patient cohort treated with hydroxychloroquine (overall response rate, ORR = 100%), who showed disease progression during CsA or retinoids. Conclusions: Our results from this contemporary cohort of patients with LPP and FFA indicate that hydroxychloroquine and cyclosporine are effective systemic agents in decreasing clinical symptoms. However, our data also show that the discontinuation of treatment is often associated with the exacerbation of clinical symptoms. Response rates to second-line treatment were especially favorable in the patient cohort with hydroxychloroquine. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is characterized by microinflammation and abnormal immune responses, particularly in the upper segment of hair follicles (HFs). However, the precise patterns of immune dysregulation remain unclear, partly due to limitations in current analysis techniques to preserve tissue architecture. The infundibulum, a major part of the upper segment of HFs, is associated with significant clusters of immune cells. In this study, we investigated immune cells around the infundibulum, referred to as peri-infundibular immune infiltration (PII). We employed spatial transcriptome profiling, a high-throughput analysis technology, to investigate the immunological disruptions within the PII region. Our comprehensive analysis included an evaluation of overall immune infiltrates, gene set enrichment analysis (GSEA), cellular deconvolution, differential expression analysis, over-representation analysis, protein-protein interaction (PPI) networks, and upstream regulator analysis to identify cell types and molecular dysregulation in immune cells. Our results demonstrated significant differences in immune signatures between the PII of AGA patients (PII-A) and the PII of control donors (PII-C). Specifically, PII-A exhibited an enrichment of CD4+ helper T cells, distinct immune response patterns, and a bias toward a T helper (Th) 2 response. Immunohistochemistry revealed disruptions in T cell subpopulations, with more CD4+ T cells displaying an elevated Th2 response and a reduced Th1-cytotoxic response compared to PII-C. These findings reveal the unique immune landscapes of PII-A and PII-C, suggesting potential for the development of innovative treatment approaches. [ABSTRACT FROM AUTHOR]

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Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma thought to arise via either viral (Merkel cell polyomavirus) or ultraviolet-associated pathways. Surgery and radiotherapy have historically been mainstays of management, and immunotherapy has improved outcomes for advanced disease. However, there remains a lack of effective therapy for those patients who fail to respond to these established approaches, underscoring a critical need to better understand MCC biology for more effective prognosis and treatment. Here, we review the fundamental aspects of MCC biology and the recent advances which have had profound impact on management. The first genetically-engineered mouse models for MCC tumorigenesis provide opportunities to understand the potential MCC cell of origin and may prove useful for preclinical investigation of novel therapeutics. The MCC cell of origin debate has also been advanced by recent observations of MCC arising in association with a clonally related hair follicle tumor or squamous cell carcinoma in situ. These studies also suggested a role for epigenetics in the origin of MCC, highlighting a potential utility for this therapeutic avenue in MCC. These and other therapeutic targets form the basis for a wealth of ongoing clinical trials to improve MCC management. Here, we review these recent advances in the context of the existing literature and implications for future investigations. [ABSTRACT FROM AUTHOR]

Background: Female‐pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles. Objective: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL]. Methods: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included. We identified 120 patients from our database who fulfilled the inclusion and exclusion criteria, and patients were then categorized into two groups, Group A comprising patients who were taking 100 mg of spironolactone once daily and Group B comprising patients who were taking 50 mg of bicalutamide once daily along with topical minoxidil 2% in both groups. Patient were analysed at approximately at 24 weeks from the commencement of the treatment. Results: Mean reduction in hair loss severity score on Sinclair scale was 19.51% in spironolactone group compared to 28.20% in bicalutamide group at 24 weeks, which was statistically significant. On global photographic assessment, marked improvement was seen in bicalutamide group compared to spironolactone group (p = 0.139). Conclusions: Our study, though limited by its retrospective design and small sample size, showed that bicalutamide has greater efficacy and better safety profile in comparison to spironolactone in the treatment of FPHL. [ABSTRACT FROM AUTHOR]

This article discusses a case of normolipemic xanthoma associated with folliculotropic mycosis fungoides (fMF), a variant of mycosis fungoides. The patient, a 60-year-old Japanese man, presented with yellowish masses and patchy alopecia on the scalp, as well as follicular papules on the trunk and extremities. Trichoscopy and histological analysis revealed mucin deposition, lymphocyte and eosinophil infiltrations, and dense infiltration of histiocytes mixed with eosinophils and lymphocytes. The article suggests that the tumour microenvironment triggers histiocyte infiltration, which may lead to xanthoma formation. The case highlights the challenges in diagnosing fMF due to excessive granulomatous/xanthomatous components and emphasizes the importance of a comprehensive assessment for a definitive diagnosis. [Extracted from the article]

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy. [ABSTRACT FROM AUTHOR]

Alopecia affects patients' appearance and psychology. Mixed-lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis plays a role in various skin diseases, but its effect on hair growth is unclear. To investigate the effects of MLKL on hair growth and its regulatory mechanisms and to determine the potential clinical value of Necrosulfonamide (NSA, a MLKL-targeting inhibitor) in promoting hair growth and counteracting dihydrotestosterone (DHT) inhibition of hair growth. The expression level of MLKL was detected in the scalp of androgenetic alopecia (AGA) patients and the skin tissues of mice. Knock down MLKL expression or use NSA to observe hair growth in vivo and in vitro. In AGA patients, MLKL expression is elevated in the alopecia areas. In mice, MLKL is significantly expressed in the outer root sheath (ORS) cells of hair follicles, peaking during the catagen phase. Knockdown expression of MLKL in mice skin promoted hair growth. NSA enhanced hair growth and prevented hair follicle regression via the Wnt signaling. Reduced MLKL boosts ORS cell proliferation without directly impacting DPCs' growth. Interestingly, NSA boosts DPCs' proliferation and induction when co-cultured with ORS cells. Besides, NSA alleviated the inhibition of DHT on hair growth in vivo and vitro. NSA inhibited the activation of MLKL in ORS cells, promoted the activation of Wnt signal in DPC cells, and improved the inhibition of hair growth by DHT, illuminating a new alopecia mechanism and aiding anti-alopecia drug development. • MLKL was significantly upregulated in alopecia area in AGA patients. • MLKL knockdown or inhibition promoted hair growth. • NSA inhibits MLKL activation to promote hair growth. • NSA limits MLKL activity in ORS to foster proliferation and induce ability of DPC. • NSA ameliorates DHT-induced hair growth inhibition. [ABSTRACT FROM AUTHOR]

Cashmere goats possess two types of hair follicles, with the secondary hair follicles producing valuable cashmere fiber used for textiles. The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. Transcription factors play crucial roles during this process. The transcription factor, cold-shock domain, containing C2 (Csdc2) plays a crucial role in modulating cell proliferation and differentiation. Our preceding research indicated that the expression of Csdc2 changes periodically during anagen to telogen. However, the mechanisms of Csdc2 in regulating SHF growth remain unclear. Here, we found that the knockdown of Csdc2 inhibits the proliferation of dermal papilla cells. ChIP-Seq analysis showed that Csdc2 had a unique DNA binding motif in SHFs. Through conjoint analysis of ChIP-Seq and RNA-Seq, we revealed a total of 25 candidate target genes of Csdc2. Notably, we discovered a putative Csdc2 binding site within roundabout guidance receptor 2 (Robo2) on chromosome 1 of the goat genome. Furthermore, qRT-PCR and dual-luciferase reporter assay confirmed Csdc2's positive regulatory influence on Robo2. These findings expand the research field of hair follicle transcriptional regulatory networks, offering insights into molecular breeding strategies to enhance cashmere production in goats. [ABSTRACT FROM AUTHOR]

The hair follicle is the basis of hair regeneration, and the dermal papilla is one of the most important structures in hair regeneration. New intervention and reversal strategies for hair loss may arise due to the prevention of oxidative stress. GC/MS analysis was used to determine the compounds contained in NSO. Then, NSO was applied to DPC for cell proliferation and oxidative stress experiments. RNA-seq was performed in cells treated with NSO and minoxidil. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the gene expression. The effects of NSO on hair length, weight, the number and depth of hair follicles, and the dermal thickness were also studied. GC/MS analysis showed that the main components of NSO were eicosapentaenoic acid, palmitic acid, and linoleic acid. NSO promotes DPC proliferation and reduces H2O2-mediated oxidative damage. NSO can also activate hair growth-related pathways and upregulate antioxidant-related genes analyzed by gene profiling. The topical application of NSO significantly promotes hair growth and increases hair length and weight in mice. NSO extract promotes hair growth and effectively inhibits oxidative stress, which is beneficial for the prevention and treatment of hair loss. [ABSTRACT FROM AUTHOR]

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti‐inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro‐inflammatory cytokines IL‐1β to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17β‐Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pilomatricoma, a rare benign skin tumor arising from hair follicle matrix cells, warrants consideration in the evaluation of subcutaneous nodules or masses, especially when presenting as painless and firm lesions. Accurate diagnosis hinges on histopathological examination, underscoring the significance of clinician vigilance and prompt intervention. Pilomatricoma, also referred to as Pilomatrixomas or Calcifying epithelioma of Malherbe, is a rare benign skin tumor derived from hair follicle matrix cells, presents a diagnostic challenge due to its diverse clinical manifestations. Females are more commonly affected by Pilomatricoma. This condition typically manifests as a painless, firm, and slowly progressive lesion. Histopathological analysis shows characteristic findings, such as basaloid cells at the periphery and shadow cells centrally. Immunohistochemical studies assess the expression of cytokeratin's associated with hair matrix differentiation. Complete surgical excision remains the cornerstone of treatment, ensuring favorable outcomes and minimizing the risk of recurrence. Awareness of this entity among clinicians is essential for timely recognition and appropriate intervention. In this specific case‐study, we present a case of Pilomatricoma situated in the lower left orbital region of a 32‐year‐old male individual who had been noticing swelling in that vicinity over the preceding 7 months. [ABSTRACT FROM AUTHOR]

This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 μm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki‐67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure. [ABSTRACT FROM AUTHOR]

Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF‐1, FGF and irisin are reprehensive myokines. Although VEGF, IGF‐1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/β‐catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF‐1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/β‐catenin signalling inhibitor, suppressed the irisin‐mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/β‐catenin pathway and highlight its therapeutic potential in hair loss treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess differences in various scalp parameters between patients with androgenetic alopecia (AGA) and healthy volunteers using 22 MHz ultrasound. Methods: Thirty patients with AGA (AGA group) and 30 healthy volunteers (control group) who visited the Department of Dermatology at the Second Affiliated Hospital of Soochow University from September 2021 to June 2022 were randomly selected. The patients with AGA met the diagnostic criteria outlined in the Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia. The severity of alopecia was assessed for males between grades 2 and 4 on the Norwood–Hamilton scale, and for females between stages 2 and 3 on the Ludwig scale. No artificial interventions were conducted at the vertex, and all examination conditions remained consistent. Ultrasound examinations at 22 MHz were performed on the scalp at the vertex in both the AGA and control groups. Seven parameters were measured, namely, epidermis + dermis thickness, entire scalp thickness, subcutaneous tissue thickness, average follicle width, average follicle length, follicle count, and the presence of color flow signals in the subcutaneous tissue. The differences in these parameters were then compared. Results: The AGA group showed reduced thickness of the entire scalp and subcutaneous tissue, narrower average follicle width, shorter average follicle length, lower hair follicle count, and fewer instances of color flow signals in the subcutaneous tissue at the vertex area (p < 0.05). Conclusion: High‐frequency (22 MHz) ultrasonography can be employed to visualize the entrance echo, dermis, subcutaneous tissue, and hair follicles of the scalp, thereby providing imaging for the clinical assessment of hair loss. [ABSTRACT FROM AUTHOR]

Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8+NKG2D+T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata. Reversal of alopecia areata with topical TFB NPs treatment by blocking the JAK-STAT signaling pathways, reduced the expression levels of IFN-γ and the frequencies of NKG2D+CD8+ T cells, restored immune environment and promoted hair regrowth. [Display omitted] • Ex vivo mouse hair follicles model was used to assess formulations. • Hair follicles blocked skin model was used to evaluate drug permeation. • Cationic nanostructured carriers minimize systemic circulation and maximize hair follicle targeting. • The formulation restored immune privilege and ensured safe topical delivery for the treatment of alopecia areata. [ABSTRACT FROM AUTHOR]

The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing–thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20℃ for 9 days: thawed at 4℃, room temperature (RT), and 32℃. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32℃. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing–thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs. [ABSTRACT FROM AUTHOR]

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics powered by skin tissue engineering offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth. [ABSTRACT FROM AUTHOR]

Our research focuses on evaluating the preliminary stability of solid lipid nanoparticles (SLNs) in order to identify an optimal formulation for studying the skin penetration of SLNs loaded with sesamol, with a view to developing potential cosmetic applications. For this study, SLNs were prepared with varying lipid and surfactant compositions and produced through homogenization and ultrasonication. The particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were analyzed for the different formulations. We identified OP2Se as the optimal formulation for skin penetration assessment due to its stable PS, PDI, ZP, and EE over time, with a Turbiscan Stability Index (TSI) below 1 after a month, indicating favorable stability conditions. The in vitro skin permeation study compared sesamol-loaded SLNs with a control sesamol hydrogel, revealing controlled release characteristics ideal for localized skin effects without significant bloodstream penetration, attributed to the SLNs' 200 nm particle size. Further exploration could enhance skin retention and targeting, potentially extending penetration studies and reducing particle size to improve accumulation in hair follicles. Exploring SLN applications beyond sesamol, such as incorporating mineral filters for suncare, offers promising avenues, underscoring SLNs' versatility in cosmetic formulations and skincare applications. [ABSTRACT FROM AUTHOR]

Alopecia is traditionally viewed as androgen-dependent, but emerging evidence has implicated oxidative stress in the pathogenesis of hair loss. Current treatments for alopecia have limited efficacy, leading to the need for new therapies. Human dermal papilla cells (hDPCs) play a pivotal role in hair follicle (HF) development and hair growth regulation. In this study, we investigated the potential of (S)-3-((S)-2-(6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxoisoindolin-2-yl)butanamido)-4-oxo-5-(2,3,5,6 tetrafluorophenoxy) pentanoic acid (THPA), a pan-caspase inhibitor, to reduce ROS-induced cellular damage and apoptosis in hDPCs. Our study revealed that THPA effectively suppressed hydrogen peroxide-induced apoptosis while also attenuating activated caspase signaling. Additionally, THPA restored the down-regulated expression of β-catenin, a key mediator of the Wnt/β-catenin pathway, in hDPCs exposed to hydrogen peroxide. Furthermore, significant alterations in Akt/mTOR/p70S6K signaling were observed following THPA treatment. Notably, THPA treatment led to a reduction in the expression of Dickkopf-1 (DKK-1), an inhibitor of the Wnt/β-catenin pathway implicated in hair follicle regression. Moreover, THPA treatment decreased the expression of the cell senescence markers p21 and p16, suggesting a potential role in preserving hDPC function and delaying hair follicle regression. Collectively, our findings highlight the therapeutic potential of THPA in preventing hair loss by protecting hDPCs against oxidative stress damage. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic wounds present a growing challenge in the aging population, resulting in an extended course of treatment and an increased influx of patients with recalcitrant wounds seeking admission to hospitals. Furthermore, the general trend in patient care is toward simple and inexpensive treatment methods, feasible in an outpatient setting with little material costs. This retrospective case study aims to elucidate the operative procedure and outcomes associated with hair follicle unit transplantation utilizing punch grafts from the scalp for the management of hard‐to‐heal wounds. Methods: A cohort of 28 patients, comprising 20 males and eight females, with a mean age of 72.61 years (range: 48−89) and an average wound area of 82.49 cm2, underwent dissection of punch grafts containing hair follicles (2−3 mm in diameter) from the scalp. Subsequently, these grafts were transplanted into the wound bed. The retrospective evaluation of ulcer healing encompassed photo documentation and clinical records, while patient satisfaction was assessed through structured questionnaires. Results: In 78.6% (22) of the cases, a favorable impact on wound healing was observed, characterized by epithelization, and in 57.1% (16) of the patients, complete wound closure was achieved. With the exception of one donor site, all other sites healed without complications. The patient survey indicated that the majority of individuals subjected to the procedure did not perceive it as painful or time‐consuming. Notably, 81% (17) of individuals expressed a willingness to undergo the treatment again. Even in challenging wound conditions, such as pyoderma gangrenosum, our method demonstrated a positive effect on wound healing. Conclusion: Within our cohort, the utilization of hair follicle units in the management of hard‐to‐heal wounds resulted in either complete or partial wound closure for the majority of patients, accompanied by minimal morbidity, reduced operation time, and a low incidence of complications and associated costs. [ABSTRACT FROM AUTHOR]

Background Aims Methods Results Conclusions Androgenetic alopecia (AGA) is common. While topical minoxidil remains the only FDA‐approved therapeutic for AGA, its efficacy is limited in stimulating clinically significant hair regrowth over the longer term. Oral minoxidil, which is used off‐label, is a promising alternative; however, its effectiveness and underlying mechanisms warrant further investigation.To elucidate the site of action and infer the physiological mechanisms underlying therapeutic responses to oral minoxidil in patients with AGA.Forty‐one patients with AGA underwent 6 months of low‐dose oral minoxidil treatment. Minoxidil sulfotransferase (SULT) activity was assayed in plucked scalp hair follicles. The primary outcome was hair growth after low‐dose oral minoxidil treatment for a minimum of 6 months, and the secondary outcome was SULT activity in hair follicles.After 6 months of treatment, 26 (63.4%) patients experienced a clinical improvement in alopecia symptoms. The response rate was higher in men (19/26 [73.1%]) than in women (6/15 [40.0%]). Patients with low hair follicle SULT activity demonstrated a higher minoxidil response rate than those with high enzyme activity (85% vs. 43%, p = 0.009).Our findings indicate that low SULT activity within the hair follicles is associated with a favorable response to oral minoxidil therapy in patients with AGA. Further elucidation of the underlying mechanisms could significantly improve personalized therapeutic approaches through improved patient selection and the rational design of adjuvant treatments. [ABSTRACT FROM AUTHOR]

The terms “onychofibroblast” (nail‐specific fibroblast) and onychodermis (nail‐specific dermis) were first introduced in 2006 and 2012, respectively, based on distinctive histologic and immunohistochemical features from the dermis of the surrounding skin and have been demonstrated in multiple studies. Recently, based on molecular research, the definition of onychodermis containing onychofibroblasts has been expanded to encompass the area located between the nail matrix and bed epithelium and periosteum. Single‐cell RNA sequencing and in situ hybridization demonstrated that onychofibroblasts within the onychodermis express the genes including RSPO4, MSX1, WIF‐1, and BMP5, which are implicated in nail formation and/or in disorders with nail phenotype. A mutation in RSPO4, a component of the Wnt signaling pathway, causes anonychia congenita. Nail matrix onychodermis and nail bed onychodermis share many similar characteristics which differ from the surrounding normal dermis of the skin. Comparative spatial transcriptomic and single‐cell analyses of human nail units and hair follicles suggest that onychodermis is the counterpart of follicular dermal papilla, which plays a key role in hair follicle growth and morphogenesis. Onychomatricoma, as a nail‐specific tumor, has been demonstrated to be a mesenchymal tumor that originates from onychofibroblasts and is associated with the upregulation of Wnt signaling. Collectively, the onychodermis and onychofibroblasts play crucial roles in nail development and these specialized nail mesenchymal elements are key components in the pathogenesis of onychomatricoma. The concept of onychodermis containing onychofibroblasts is very important for nail biology and pathology. [ABSTRACT FROM AUTHOR]

Background: Angrogenetic alopecia (AGA) is one of the most prevalent hair loss disorders worldwide. The hair follicle stem cell (HFSC) is closely related to the formation of hair follicle (HF) structure and HF self-renewal. The activation of HFSC in AGA is critical for hair growth. Pilose antler has been reported to have hair growth-promoting activity, but the mechanism of action on AGA and HFSC has not been reported. Methods: We previously extracted an active component from the pilose antler known as PAEs. In this study, we conducted experiments using AGA mice and HFSC. The effects of PAEs on hair growth in AGA mice were firstly detected, and then the mechanisms of PAEs for AGA were predicted by integrating network pharmacology and de novo transcriptomics data of pilose antler. Finally, biological experiments were used to validate the molecular mechanism of PAEs in treating AGA both in vivo and in vitro. Results: It was found that PAEs promoted hair regrowth by accelerating the activation of anagen, delaying the anagen-catagen transition. It also alleviated the morphological changes, such as hair shortening, thinning, miniaturization, and HF number reduction, and regulated the hair regeneration process of four subtypes of hair. We further found that PAEs could promote the proliferation of HFSC, outer root sheath (ORS) cells, and hair bulb cells in AGA mice. We then integrated network pharmacology and pilose antler transcriptomics data to predict that the mechanism of PAEs treatment in AGA mice is closely related to the PI3K-AKT/Wnt-ß-Catenin pathways. Subsequently, it was also verified that PAEs could activate both pathways in the skin of AGA mice. In addition, we found that PAEs perhaps increased the number of blood vessels around dermal papilla (DP) in experiments in vivo. Meanwhile, the PAEs stimulated the HFSC proliferation in vitro and activated the AKT and Wnt pathways. However, the proliferative activity of HFSC was inhibited after blocking the Wnt pathway and AKT activity. Conclusion: This study suggests that the hair growth-promoting effect of PAEs in AGA mice may be closely related to the stimulation of the AKT and Wnt pathways, which in turn activates the proliferation of HFSC. [ABSTRACT FROM AUTHOR]

Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors β-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/β-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing. [ABSTRACT FROM AUTHOR]

Sheep body size can directly reflect the growth rates and fattening rates of sheep and is also an important index for measuring the growth performance of meat sheep. Inner Mongolia Cashmere Goat is a local excellent breed of cashmere and meat dual-purpose, which is a typical heterogeneous indumentum. The hair follicles cycle through periods of vigorous growth (anagen), a regression caused by apoptosis (catagen), and relative rest (telogen). At present, it is not clear which genes affect the cycle transformation of hair follicles and unclear how proteins impact the creation and expansion of hair follicles. we using multi-omics joint analysis methodologies to investigated the possible pathways of transformation and apoptosis in goat hair follicles. The results showed that 917,1,187, and 716 proteins were specifically expressed in anagen, catagen andtelogen. The result of gene ontology (GO) annotation showed that differentially expressed proteins (DEPs) are in different growth cycle periods, and enriched GO items are mostly related to the transformation of cells and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment result indicated that the apoptosis process has a great impact on hair follicle's growth cycle. The results of the protein interaction network of differential proteins showed that the ribosomal protein family (RPL4, RPL8, RPS16, RPS18, RPS2, RPS27A, RPS3) was the core protein in the network. The results of combined transcriptome and proteomics analysis showed that there were 16,34, and 26 overlapped DEGs and DEPs in the comparison of anagen VS catagen, catagen VS telogen and anagen VS telogen, of which API5 plays an important role in regulating protein and gene expression levels. We focused on API5 and Ribosomal protein and found that API5 affected the apoptosis process of hair follicles, and ribosomal protein was highly expressed in the resting stage of hair follicles. They are both useful as molecular marker candidate genes to study hair follicle growth and apoptosis, and they both have an essential function in the cycle transition process of hair follicles. The results of this study may provide a theoretical basis for further research on the growth and development of hair follicles in Inner Mongolian Cashmere goats. [ABSTRACT FROM AUTHOR]

Simple Summary: Depilation is a well-established method for synchronizing the hair growth in mice which is valuable to test hair growth interventions. However, our experience with the previously published depilation protocols showed that upon depilation mice developed wounds. Here, we propose a new depilation method that protects the mouse skin, minimizing skin injuries and improving not only experimental conditions but also animal welfare. We test this new protocol not only in C57BL/6J mice, the most commonly used strain in hair growth pre-clinical studies, but also in other two strains (Sv129 and B6129F1), which lack a well-characterized hair growth cycle. Our results show that hair cycle kinetics are similar in all the analyzed strains, but Sv129 and B6129F1 skins are morphologically different from C57BL/6J skin, presenting increased number and size of hair follicles in anagen, consistent to the higher hair density observed macroscopically. This study reveals a new method to improve animal hair research and characterizes the hair growth in two different strains, enhancing their suitability in future studies. In mice, hair growth follows a mosaic or wavy patterning. Therefore, synchronization of the hair growth cycle is required to adequately evaluate any trichogenic interventions pre-clinically. Depilation is the established method for synchronizing the growth phase of mouse hair follicles. When attempting to reproduce procedures reported in the literature, C57BL/6J mice developed severe wounds. This led us not only to optimize the procedure, but also to test the procedure in other strains, namely Sv129 and the F1 generation from C57BL/6J crossed with Sv129 (B6129F1 mixed background), for which the hair growth cycle has not been ascertained yet. Here, we describe an optimized depilation procedure, using cold wax and an extra step to protect the animal skin that minimizes injury, improving experimental conditions and animal welfare in all strains. Moreover, our results show that, although hair cycle kinetics are similar in all the analyzed strains, Sv129 and B6129F1 skins are morphologically different from C57BL/6J skin, presenting an increased number and size of hair follicles in anagen, consistent to the higher hair density observed macroscopically. Altogether, the results disclose an optimized mouse depilation method that excludes the detrimental and confounding effects of skin injury in hair growth studies and reveals the hair cycle features of other mouse strains, supporting their use in hair growth pre-clinical studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Inner Mongolia Albas white cashmere goat is a unique biological resource in Northwest China, and the cashmere produced by goat is sold well at home and abroad because of its softness and warmth. Cashmere is the product of the growth and development of secondary hair follicles, and dermal papilla cells (DPCs) are the seeds of hair follicle growth and development, which are regulated by a variety of factors in growth and development. At present, the regulation mechanism of Shh gene on DPCs of secondary hair follicles in cashmere goats is not clear. In this study, we found that Shh gene expression was significantly higher in anagen than in catagen and telogen in the secondary hair follicles of cashmere goats, and the proliferation and viability of DPCs after overexpressing Shh gene were increased, whereas the apoptosis of DPCs after interfering with Shh gene was elevated. In addition to this, we demonstrated that Shh gene promotes the expression of the related genes Ptched (Ptch), Smoothened (Smo), and GLI Family Zinc Finger 2 (Gli2) in the Hedgehog signaling pathway. Therefore, this study reveals that Shh regulates the genes related to the Hedgehog signaling pathway to affect the proliferation and apoptosis of dermal papilla cells, leading to the differential expression of the Shh gene in the secondary hair follicle growth cycle of cashmere goats. The result is of great significance for the study of the pathway regulation mechanism of secondary hair follicles in cashmere goat and provides a theoretical direction for the positive development of the cashmere industry. Sonic hedgehog (Shh) is a component of the Hedgehog signaling pathway, playing an important role in regulating cell proliferation, differentiation, apoptosis, and the repair of damaged organisms. To further clarify the expression pattern of Shh gene in the secondary hair follicle growth cycle of cashmere goats and its mechanism of action on secondary hair follicle papilla cells, and improve cashmere quality, in this study, we took Inner Mongolia Albas white cashmere goats as the research objects and collected skin samples at different growth stages to obtain secondary hair follicles, detected Shh and its gene expression by RT-qPCR, Western blot, immunohistochemistry, and other techniques, while we also cultured DPCs in vitro. Shh gene overexpression and interference vectors were constructed, and the effects of Shh gene on the proliferation and apoptosis of DPCs were studied through cell transfection technology. The results showed that there are significant differences in Shh and its gene expression in the secondary hair follicle growth cycle skins of cashmere goats, with the highest expression level in anagen, followed by catagen, and the lowest expression level in telogen. Shh was mainly expressed in the inner root sheath, outer root sheath, and secondary hair follicle papilla. After the overexpression of Shh gene, the proliferation and vitality of the hair papilla cells were enhanced compared to the interference group. After Shh gene interference, the apoptosis rate of the cells increased, indicating that Shh gene can regulate downstream Ptch, Smo, and Gli2 gene expression to promote the proliferation of DPCs, and thus form its expression pattern in the secondary hair follicle growth cycle of cashmere goats. [ABSTRACT FROM AUTHOR]

Wool is generated by hair follicles (HFs), which are crucial in defining the length, diameter, and morphology of wool fibers. However, the regulatory mechanism of HF growth and development remains largely unknown. Dermal papilla cells (DPCs) are a specialized cell type within HFs that play a crucial role in governing the growth and development of HFs. This study aims to investigate the proliferation and induction ability of ovine DPCs to enhance our understanding of the potential regulatory mechanisms underlying ovine HF growth and development. Previous research has demonstrated that microRNA-181a (miR-181a) was differentially expressed in skin tissues with different wool phenotypes, which indicated that miR-181a might play a crucial role in wool morphogenesis. In this study, we revealed that miR-181a inhibited the proliferation and induction ability of ovine DPCs by quantitative Real-time PCR (qRT-PCR), cell counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, and alkaline phosphatase staining. Then, we also confirmed G protein subunit alpha i2 (GNAI2) is a target gene of miR-181a by dual luciferase reporter assay, qRT-PCR, and Western blot, and that it could promote the proliferation and induction ability of ovine DPCs. In addition, GNAI2 could also activate the Wnt/β-Catenin signaling pathway in ovine DPCs. This study showed that miR-181a can inhibit the proliferation and induction ability of ovine DPCs by targeting GNAI2 through the Wnt/β-Catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) is the most common type of alopecia and its treatments involve drugs that have various adverse effects and are not completely effective. Radiofrequency-based therapies (RF) are an alternative for AGA treatment. Although there is increasing clinical evidence of the effectiveness of RF for alopecia, its effects at the tissue and cellular level have not been studied in detail. The objective of this study was to analyze ex vivo the potential effect of RF currents used in capacitive resistive electrical transfer (CRET) therapy on AGA. Hair follicles (HFs) were donated by patients with AGA and treated with CRET. AGA-HFs were exposed in vitro to intermittent 448 kHz electric current in subthermal conditions. Cell proliferation (Ki67), apoptosis (TUNEL assay), differentiation (β-catenin), integrity (collagen and MMP9), thickness of the epidermis surrounding HF, proportion of bulge cells and melanoblasts in AGA-HF were analyzed by immunohistochemistry. CRET increased proliferation and decreased death of different populations of AGA-HF cells. In addition, the melanoblasts increased in bulge and the epidermis surrounding the hair follicle thickened. These results support the effectiveness of RF-based therapies for the treatment of alopecia. However, clinical trials are necessary to know the true effectiveness of CRET therapy and other RF therapies for AGA treatment. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia is a genetic disorder that commonly causes progressive hair loss in men, leading to diminished self-esteem. Although cannabinoids extracted from Cannabis sativa are used in hair loss treatments, no study has evaluated the effects of germinated hemp seed extract (GHSE) and exosomes derived from the calli of germinated hemp seeds on alopecia. Therefore, this study aimed to demonstrate their preventive effects against alopecia using various methodologies, including quantitative PCR, flow cytometry, ELISA, and immunocytochemistry. Our research highlights the preventive functions of GHSE (GE2000: 2000 µg/mL) and exosomes from the calli of germinated hemp seeds (E40: 40 μg/mL) in three biochemical categories: genetic modulation in hair follicle dermal papilla stem cells (HFDPSCs), cellular differentiation, and immune system modulation. Upon exposure to dihydrotestosterone (DT), both biomaterials upregulated genes preventing alopecia (Wnt, β-catenin, and TCF) in HFDPSCs and suppressed genes activating alopecia (STAT1, 5α-reductase type 1, IL-15R). Additionally, they suppressed alopecia-related genes (NKG2DL, IL2-Rβ, JAK1, STAT1) in CD8+ T cells. Notably, E40 exhibited more pronounced effects compared to GE2000. Consequently, both E40 and GE2000 effectively mitigated DT-induced stress, activating mechanisms promoting hair formation. Given the limited research on alopecia using these materials, their pharmaceutical development promises significant economic and health benefits. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate circadian rhythms in independently living adults with obesity and mental disease, exploring the interplay between biological markers and lifestyle factors. Eighty participants divided equally into four groups; (i) people with obesity and schizophrenia; (ii) people with obesity and bipolar disorder; (iii) people with obesity without mental disease or sleep disorders, and (iv) people without obesity, mental disease or sleep disorders. Over two consecutive days, participants engage in repeated self-sampling of hair follicle and saliva; concurrently, data is collected on diet, body temperature, light exposure, sleep parameters, and physical activity by accelerometry. Hair follicles are analyzed for circadian gene expression, saliva samples for cortisol and melatonin concentrations. Circadian rhythms are investigated by cosinor analysis. The study employs a participant-tailored sampling schedule to minimize disruptions to daily routine and enhance ecological validity. The methodology aims to provide a comprehensive insight into the factors contributing to circadian disruptions in people with obesity, bipolar disorder and schizophrenia, potentially informing strategies for future management and mitigation. Trial registration: (ClinicalTrials.gov Identifier: NCT05413486). [ABSTRACT FROM AUTHOR]

Motivation The burgeoning generation of single-cell or spatial multiomic data allows for the characterization of gene regulation networks (GRNs) at an unprecedented resolution. However, the accurate reconstruction of GRNs from sparse and noisy single-cell or spatial multiomic data remains challenging. Results Here, we present SCRIPro, a comprehensive computational framework that robustly infers GRNs for both single-cell and spatial multiomics data. SCRIPro first improves sample coverage through a density clustering approach based on multiomic and spatial similarities. Additionally, SCRIPro scans transcriptional regulator (TR) importance by performing chromatin reconstruction and in silico deletion analyses using a comprehensive reference covering 1292 human and 994 mouse TRs. Finally, SCRIPro combines TR-target importance scores derived from multiomic data with TR-target expression levels to ensure precise GRN reconstruction. We benchmarked SCRIPro on various datasets, including single-cell multiomic data from human B-cell lymphoma, mouse hair follicle development, Stereo-seq of mouse embryos, and Spatial-ATAC-RNA from mouse brain. SCRIPro outperforms existing motif-based methods and accurately reconstructs cell type-specific, stage-specific, and region-specific GRNs. Overall, SCRIPro emerges as a streamlined and fast method capable of reconstructing TR activities and GRNs for both single-cell and spatial multiomic data. Availability and implementation SCRIPro is available at https://github.com/wanglabtongji/SCRIPro. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata (AA) is an autoimmune disease of the hair follicles. Although some cases resolve spontaneously, many patients require some form of treatment, including corticosteroids and vitamin D analogues, among others. Cytokine signaling in autoimmune disorders and their inhibition have been the prime objective in therapeutic research over the past few years. Janus kinase inhibitors such as tofacitinib have shown efficacy in the treatment of AA. The present study aimed to evaluate the efficacy of a novel formulation of topical tofacitinib compared to vehicle in patients with AA. Materials and Methods: A prospective, non‑blinded, intrasubject vehicle‑controlled study was conducted in patients with AA for a total duration of 6 months. A 2% tofacitinib citrate ointment was compounded in the pharmacy. Tofacitinib tablets (5 mg) were crushed and mixed in white soft paraffin to produce 2% ointment. A thin layer of this ointment was applied to the treatment patch, while the control patches received the application of the vehicle twice daily. Both patches in each patient were evaluated for percentage change in severity of alopecia tool [SALT] score after 24 weeks as the primary outcome. This was graded as excellent response (>50% improvement), intermediate response (25–50%), mild response (5–25%), and no response (<5% improvement). Trichoscopy and hair pull test were evaluated as secondary outcomes. Results: The present study included 30 patients with AA having a median age of 27 years. Among 30 patients, 40% achieved excellent response (>50% change in the SALT score) over six months of treatment. The mean SALT score was significantly reduced from baseline to six months of treatment (mean [95% CI]: 4.3 [1.9–6.3]; P = 0.001). The control patch had substantially higher positive results in the final hair pull test, indicating disease activity (Treatment: 10% vs. Control: 86.7%, P < 0.001). Compared to the control patch, the prevalence of upright hair (10.0% vs. 80.0%) and terminal hair (3.3% vs. 70.0%) were significantly higher in the treatment patch (P < 0.001). No serious adverse effects were reported during the study duration. Limitations: Sample size was small and the followup was not long enough to study the full effects of tofacitinib, as well as maintenance of remission or relapse after discontinuation. Conclusion: Topical tofacitinib proved to be an efficacious and well‑tolerated treatment modality for AA with no adverse effects reported during this study. [ABSTRACT FROM AUTHOR]

The wound-healing process is a paradigm of the directed migration of various pools of stem cells fromtheir niche to the site of injury where they replenish damaged cells. Two decades have elapsed since the observation that wounding activates multipotent hair follicle stem cells to infiltrate the epidermis, but the cues that coax these cells out of their niche remain unknown. Here, we report that Caspase-1, a protein classically known as an integral component of the cytosolic inflammasome, is secreted upon wounding and has a non-canonical role in the extracellular milieu. Through its caspase activation recruitment domain (CARD), Caspase-1 is sufficient to initiate the migration of hair follicle stem cells into the epidermis. Uncovering this novel function of Caspase-1 also facilitates a deeper understanding of the mechanistic basis of the epithelial hyperplasia found to accompany numerous inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Background: The cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits. Results: We estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109–1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 < PIC < 0.25), and the polymorphic information content of 79 SNPs were moderate polymorphism (0.25 < PIC < 0.50). We analyzed the association of SNPs with phenotypes and found that the homozygous mutant type of SNP1 and SNP3 was associated with the highest cashmere yield, the heterozygous mutant type of SNP30 was associated with the lowest cashmere thickness, the wild type of SNP76, SNP77, SNP78, SNP80, and SNP81 was associated with the highest cashmere thickness, and the wild type type of SNP137 was associated with the highest fleece length. 21 haplotype blocks and 68 haplotype combinations were constructed. Haplotypes A2A2, B2B2, C2C2, and D4D4 were associated with increased cashmere yield, haplotypes E2E2, F1F1, G5G5, and G1G5 were associated with decreased cashmere fineness, haplotypes H2H2 was associated with increased cashmere thickness, haplotypes I1I1, I1I2, J1J4, L5L3, N3N2, N3N3, O2O1, P2P2, and Q3Q3 were associated with increased cashmere length. We verified the polymorphism of 8 SNPs by KASP, and found that chr7_g.102631194A > G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P < 0.05). Conclusions: In conclusion, the genetic effect of single SNP on phenotypes is small, and SNPs are more inclined to be inherited as a whole. By constructing haplotypes from SNPs that are significantly associated with cashmere traits, it will help to reveal the complex and potential causal variations in cashmere traits of Inner Mongolia cashmere goats. This will be a valuable resource for genomics and breeding of the cashmere goat. [ABSTRACT FROM AUTHOR]

The marmoset is a fundamental nonhuman primate model for the study of aging, neurobiology, and many other topics. Genetic management of captive marmoset colonies is complicated by frequent chimerism in the blood and other tissues, a lack of tools to enable cost‐effective, genome‐wide interrogation of variation, and historic mergers and migrations of animals between colonies. We implemented genotype‐by‐sequencing (GBS) of hair follicle derived DNA (a minimally chimeric DNA source) of 82 marmosets housed at the Southwest National Primate Research Center (SNPRC). Our primary goals were the genetic characterization of our marmoset population for pedigree verification and colony management and to inform the scientific community of the functional genetic makeup of this valuable resource. We used the GBS data to reconstruct the genetic legacy of recent mergers between colonies, to identify genetically related animals whose relationships were previously unknown due to incomplete pedigree information, and to show that animals in the SNPRC colony appear to exhibit low levels of inbreeding. Of the >99,000 single‐nucleotide variants (SNVs) that we characterized, >9800 are located within gene regions known to harbor pathogenic variants of clinical significance in humans. Overall, we show the combination of low‐resolution (sparse) genotyping using hair follicle DNA is a powerful strategy for the genetic management of captive marmoset colonies and for identifying potential SNVs for the development of biomedical research models. Research Highlights: Genotype‐by‐sequencing of hair follicle DNA allows effective genetic characterization of captive marmosets for colony management.Ancestry analysis of genetic data reflects recent colony mergers and site‐specific genetic characteristics.Genetic data augments pedigree records to reveal previously unknown relationships in a captive population. [ABSTRACT FROM AUTHOR]

Traction alopecia (TA) refers to thinning hair caused by prolonged or repeated strain on hair follicles. Hairstyles associated with a higher risk of TA are common in early childhood, particularly among women. The case was presented of an otherwise healthy 7-year-old girl treated for a long time for pediculosis and seborrheic dermatitis, in which the dermoscopic demonstration of white hair casts led to the diagnosis of traction alopecia. Recognizing TA in its early and reversible phase in the pediatric population is essential, since timely interventions and counseling can prevent permanent cicatricial alopecia. [ABSTRACT FROM AUTHOR]

Melanocyte stem cells (McSCs) of the hair follicle are a rare cell population within the skin and are notably underrepresented in whole‐skin, single‐cell RNA sequencing (scRNA‐seq) datasets. Using a cell enrichment strategy to isolate KIT+/CD45− cells from the telogen skin of adult female C57BL/6J mice, we evaluated the transcriptional landscape of quiescent McSCs (qMcSCs) at high resolution. Through this evaluation, we confirmed existing molecular signatures for qMcCS subpopulations (e.g., Kit+, Cd34+/−, Plp1+, Cd274+/−, Thy1+, Cdh3+/−) and identified novel qMcSC subpopulations, including two that differentially regulate their immune privilege status. Within qMcSC subpopulations, we also predicted melanocyte differentiation potential, neural crest potential, and quiescence depth. Taken together, the results demonstrate that the qMcSC population is heterogeneous and future studies focused on investigating changes in qMcSCs should consider changes in subpopulation composition. [ABSTRACT FROM AUTHOR]