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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]

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]

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss. [ABSTRACT FROM AUTHOR]

Hair is a biofilament with unique multi-dimensional values. In human, in addition to physiologic impacts, hair loss and hair related disorders can affect characteristic features, emotions, and social behaviors. Despite significant advancement, there is a dire need to explore alternative novel therapies with higher efficacy, less side effects and lower cost to promote hair growth to treat hair deficiency. Glucocorticoid-induced leucine zipper (GILZ) is a protein rapidly induced by glucocorticoids. Studies from our group and many others have suggested that a synthetic form of GILZ, TAT-GILZ, a fusion peptide of trans-activator of transcription and GILZ, can function as a potent regulator of inflammatory responses, re-establishing and maintaining the homeostasis. In this study, we investigate whether TAT-GILZ could promote and contribute to hair growth. For our pre-clinical model, we used 9–12 week-old male BALB/c and nude (athymic, nu/J) mice. We applied TAT-GILZ and/or TAT (vehicle) intradermally to depilated/hairless mice. Direct observation, histological examination, and Immunofluorescence imaging were used to assess the effects and compare different treatments. In addition, we tested two current treatment for hair loss/growth, finasteride and minoxidil, for optimal evaluation of TAT-GILZ in a comparative fashion. Our results showed, for the first time, that synthetic TAT-GILZ peptide accelerated hair growth on depilated dorsal skin of BALB/c and induced hair on the skin of athymic mice where hair growth was not expected. In addition, TAT-GILZ was able to enhance hair follicle stem cells and re-established the homeostasis by increasing counter inflammatory signals including higher regulatory T cells and glucocorticoid receptors. In conclusion, our novel findings suggest that reprofiling synthetic TAT-GILZ peptide could promote hair growth by increasing hair follicle stem cells and re-establishing homeostasis. [ABSTRACT FROM AUTHOR]

The dehairing is one of the essential steps in the leather-making operation where the hair is removed using lime and sodium sulphide by the conventional method. In the present investigation, dehairing of goat skins has been attempted using zinc oxide and protease at the level of 0.5%, which gave satisfactory results. The DSC peaks indicated that the curve at 116.60 °C confirmed that the process is endothermic adsorbing more amount of zinc oxide favouring the dehairing process. Similarly, the TGA peaks showed that the process is a diffusion-controlled one, revealing more amount of zinc oxide has been transported to the skin sample favouring better dehairing in the experiments. SEM analysis clearly showed that control sample had long hair follicles, whereas the experimental sample showed complete removal of hair with hair bulbs, confirming that the experimental process is superior to control sample. FTIR analysis confirms the peaks in the visible in the ranges of 1630–1632 cm−1, 1544–1540 cm−1, and 1238–1236 cm−1 related to deformation vibration of N–H for amide bonds I, II, and III that facilitated better removal of interfibrillar proteins along with dermatan sulphate. The dehairing process was very effective, which can replace sodium sulphide in the considerable amount. This dehairing system reduces the pollution loads of BOD, COD, TDS, TSS to the level of 48, 37, 22, 23, respectively, over conventional lime and sodium sulphide dehairing system. The experimental leather sample revealed comparable shrinkage temperature, colour properties and physical strength properties to the control sample. [ABSTRACT FROM AUTHOR]

Introduction: Androgenetic alopecia (AGA) is one of the most common alopecia among men and women worldwide. It is a nonscarring alopecia that has a characterized pattern. In female pattern AGA, the hairline is stable but general thinning occurs most notably in the frontal region. In male‐pattern AGA, the hairline is receding and the thinning is most notable in the frontotemporal region. AGA has a complex pathogenesis and relation of subcutaneous fat in the scalp region and the miniaturization of terminal hair follicles is vague. In this study, subcutaneous fat in the frontal scalp an important region for AGA is compared to the occipital scalp that is spared in AGA. Method: Our study is a cross‐sectional study that has four groups. Male patient, female patient, male control, female control. Every group has 15 individuals. All of the people in the study are those referred to Rasoul Akram's dermatology clinic. The severity of alopecia is classified by Norwood scaling for male pattern AGA and Ludwig scaling for female pattern AGA. Subcutaneous tissue in the frontal and occipital regions is measured by ultrasonography. For evaluating the effect of aging on subcutaneous fat thickness, we subdivided any group into more than 40 years old and between 20 and 40 years old and compared these two subgroups. Results: The mean age of the three groups of male patient, female patient, and female control is 40 y/o and the mean age of male control is 41 y/o. The mean subcutaneous fat layer thickness in frontal region in male patients group is 6.0 mm (more than 40 y/o = 6.6 mm, between 20 and 40 y/o = 5.5 mm), in female patients group 5.1 mm (more than 40 y/o = 5.7 mm, between 20 and 40 y/o = 4.6 mm), in the male control group is 4.4 mm (more than 40 y/o = 4.7 mm, between 20 and 40 y/o = 4 mm) and in the female control group is 4.1 mm (more than 40 y/o = 4.5 mm, between 20 and 40 y/o = 3.6 mm). The mean subcutaneous fat layer thickness in the occipital region in the male patient's group is 6.4 mm (more than 40 y/o = 6.7 mm, between 20 and 40 y/o = 6 mm), in the female patient's group 6.1 mm (more than 40 y/o = 6.5 mm, between 20 and 40 y/o = 5.7 mm), in the male control group is 6.3 mm (more than 40 y/o = 6.8 mm, between 20 and 40 y/o = 5.7 mm) and in the female control group is 6.2 mm (more than 40 y/o = 6.6 mm, between 20 and 40 y/o = 5.8 mm). Conclusion: This study demonstrates that the subcutaneous fat layer in the frontal region in both males and females is thicker in AGA patients than healthy group and the more severe the AGA, the thicker is subcutaneous layer in the frontal region. In the male patients group, the subcutaneous fat layer in the frontal region is thicker than in the female patients group but in the male and female control groups is not so different. The subcutaneous fat layer in the occipital region is thicker in older individuals in both patients and control groups but is not different when compared to AGA patients and control individuals. [ABSTRACT FROM AUTHOR]

In this study, scalp tissues from Korean adults between 20 and 80 without skin disease were used. Scalp tissues were processed, and hair follicles were isolated and cultured with different treatments (including Bioscalp, Ultra Exo Booster, and Ultra S Line Plus) from Ultra V company. Over 12 days, observations and measurements of hair follicle characteristics were recorded at intervals (Days 0, 3, 6, 9, and 12). The study assessed the impact of these substances on hair follicle growth and morphology. Bioscalp, combined with Ultra Exo Booster and Ultra S Line Plus, showed significant hair elongation in ex vivo. Preservation of hair bulb diameter was observed, indicating potential for sustained hair growth by exosome‐based products. The hair growth cycle analysis suggested a lower transition to the catagen stage in test products from Ultra V compared to non‐treated groups. The research findings indicated that the tested formulations, especially the combination of Bioscalp, Ultra Exo Booster, and Ultra S Line Plus, demonstrated significant effectiveness in promoting hair growth, maintaining the integrity of the hair bulb, and reducing the transition to the catagen stage. The study suggests promising alternative treatments for hair loss, illustrating results that were as good as those of the conventional testing product groups. [ABSTRACT FROM AUTHOR]

Background: Acne inversa (Ai, also known as hidradenitis suppurativa) is a chronic recurrent skin disease of the terminal hair follicles. It occurs after puberty and predominantly in apocrine-gland-rich intertriginous skin areas. It repeatedly causes inflammatory nodules and abscesses located deeply in the skin, which in severe cases can lead to irreversible tunnels and scar formation. Objective: To demonstrate the high relevance of general practitioners in the diagnosis and treatment of Ai patients, who are often young and under great distress. Materials and methods: Review of the evidence on the current care situation and presentation of the authors' experiences from participation in the largest German healthcare research study on Ai (EsmAiL project). Results: The average time to diagnosis for Ai is currently 9 years. Due to disease progression during this time, patients often experience irreversible physical and psychological harm. As the primary point of contact, general practitioners have a significant influence on early diagnosis and the individual course of the chronic disease. The results of the healthcare research project EsmAiL show that by specializing in Ai, a central point of contact can be created that effectively cares for patients accounting for their degree of disease severity. Conclusion: With our holistic expertise as general practitioners, we are not only in a position to provide diagnostics, but can also help as a specialized center to ensure that Ai no longer has to be a stigmatizing disease. [ABSTRACT FROM AUTHOR]

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs–PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-β1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs–PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-β1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs–PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing. [ABSTRACT FROM AUTHOR]

Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth. [ABSTRACT FROM AUTHOR]

Purpose: Alopecia significantly affects the appearance and psychology of patients, and pharmacological therapies and hair transplantation are the main treatments for alopecia, but both have limitations. This review aimed to summarize the non-pharmacological therapies that promote hair growth and regeneration. Patients and Methods: This is a non-systematic review. Multiple databases was searched with relevant data published between 1997 and 2024. Searching and screening followed the PRISMA guidelines. Results: Novel therapeutic modalities, such as gas molecules, platelet-rich plasma, laser, and microneedling, can change the microenvironment of hair follicles, activate hair follicle stem cells, and promote hair growth and regeneration. Conclusion: This paper reviews research on the application of non-pharmacological therapies in alopecia treatment and hair regeneration, with a view to providing an important basis for future research on alopecia treatment and the postoperative treatment of patients after hair transplantation. [ABSTRACT FROM AUTHOR]

Background: Woolly Hair Syndrome (WHS) is a rare birth condition that affects the structure of hair in non‐black people. The pathogenesis is not yet defined. It is postulated that the hair follicle's desmosomes (specifically desmoplaquine, placoglobin and placofilin‐1, which are cell structural proteins that keep the adhesion among close cells) would be altered in this pathology, leading to fragility in the cellular union. It is subdivided into two large groups: the localized or circumscribed variant and the generalized variant. From birth or first months of life, patients with WHS are clinically characterized by the presence of a portion or entire scalp area of very short frizzy hair, usually of a smaller diameter, brittle and lighter color. The most frequent skin manifestations are pilar keratosis and palmo‐plantar keratodermia. The diagnosis is based on the clinical findings, and it is facilitated by trichotoscopic examination. However, a definitive diagnosis of WHS requires genetic testing. Oral agenesis, enamel defects (such as hypomineralization), atypical caries, dental inclusion, and malformed pin‐shaped teeth may occur. Objective: To describe an aesthetic alternative of oral rehabilitation using the mock‐up technique in a patient with WHS. Clinical case: A 5‐year‐old female patient diagnosed with WHS from the National Institute of Child Health Nihch: Breña, Lima, who was referred from the Genetic service to the Pediatric Dentistry service in order to screen outbreaks of infection associated with odontogenic origin and dental anomalies. At the ectoscopy, a patient with short capillary length, brittle and curly hair, dry skin, and nail dystrophy was observed. At the intraoral clinical examination, anterior pieces of 52, 51, 61, 62, and enamel hypomineralization were observed in all teeth. The radiographic examination showed agenesis of parts 41, 34, and 45. Integral dental treatment was performed in the operating room under general anesthesia due to the complexity of the case. Pulpectomy in pieces 52, 51, 61, 62, post of composite resin, and rehabilitation with supra‐nanow filling resin using the mock‐up technique were proposed as alternative treatments. Conclusion: The making of supra‐nano filling resin‐based crowns using the mock‐up technique is an alternative treatment for aesthetic oral rehabilitation in deciduous dentition of patients with WHS. The aesthetic treatment was achieved using supra nano‐filling resins. After 12 months of dental treatment, a favorable response was observed, improving the chewing, phonation and aesthetics of the patient. [ABSTRACT FROM AUTHOR]

Background: A precise balance between the proliferation and differentiation of epidermal progenitors is required to achieve the barrier function during the development of epidermis. During the entire process of skin development, the newly formed basal layer cells divide, differentiate, and migrate outward to the surface of the skin, which is tightly regulated by a series of events related to cell cycle progression. The CRL4DTL complex (Cullin 4 RING ligase, in association with the substrate receptor DTL) has long emerged as a master regulator in various cellular processes, which mediates the degradation of key cell cycle proteins. However, the roles of DTL in regulating epidermal morphogenesis during skin development remain unclear. Results: We showed that DTL deficiency in epidermal progenitor cells leads to defects in epidermal stratification and loss of hair follicles accompanied by reduced epidermal progenitor cells and disturbed cell cycle progression during skin development. Transcriptome analysis revealed that p53 pathway is activated in DTL‐depleted epidermal progenitor cells. The apoptosis of epidermal cells showed in DTL deficiency mice is rescued by the absence of p53, but the proliferation and differentiation defects were p53‐independent. Conclusion: Our findings indicate that DTL plays a vital role in epidermal malformation during skin development. Key Findings: Loss of DTL in developing skin leads to defects in epidermal stratification.DTL prevents activation of p53 pathway in developing epidermal progenitors.DTL regulates the proliferation and differentiation of epidermal progenitor cells through a p53‐independent way. [ABSTRACT FROM AUTHOR]

Acne or acne vulgaris is a common skin condition caused by clogging of hair follicles or pores of oily skin. Suji (Dracaena angustifolia [Medik.] Roxb.), an Indonesian herbal plant, is used to prevent bacterial growth. The study was conducted to identify the phytochemicals of ethanol extract of suji leaves and analyze the cytotoxic and antibacterial properties against Propionibacterium acnes and Staphylococcus aureus of its nanoemulsion. The results showed that the ethanol extract of suji leaves contained active compounds of alkaloids, phenols, flavonoids, saponins, triterpenoids, and steroids which are secondary metabolites. Serum nanoemulsion showed strong antibacterial activity against Propionibacterium acnes and Staphylococcus aureus at 500 and 750 ppm. The IC50 value of MTT Assay for the cytotoxic effect of nanoemulsion of ethanol extract of suji leaves was 61.92 μg/mL, which indicated that the extract was moderately active against prepuce cells, which is used as a model of acne prone skin. Nanoemulsion of suji leaf ethanol extract has antibacterial and cytotoxic properties, so it has potential as an anti-acne agent. [ABSTRACT FROM AUTHOR]

The Koebner phenomenon (KP), also known as the isomorphic response, describes the process by which new lesions that are clinically and histologically identical to a patient's existing skin disease develop following trauma. Many skin diseases exhibit this characteristic, with variations that include possible, questionable, and pseudo-Koebner reactions, with the latter category occurring due to infectious agents seeding at a trauma site. Laser application, a type of controlled skin injury used for improving cutaneous lesions and skin rejuvenation, is also considered a form of trauma. This raises the question of whether controlled thermal injury can be regarded as a type of mechanical trauma capable of producing Koebner-related reactions. We conducted a literature review of cases or studies to identify laser-induced dermatoses that correspond to Koebner-related or pathergy reaction categories. As a whole, we identified nine case reports on true KPs, two cases on possible KPs, seventeen cases on laser-induced questionable KPs comprising cases of vasculitis, eczema or Meyerson reactions, and eruptive squamous atypia cases (ESA) as well as two pseudo-Koebner cases involving wart occurrences at laser application sites. Laser-induced Koebner reactions highlight several aspects of the KP. Firstly, the type of mechanical damage influences disease promotion, as different lasers are associated with different KPs. For example, hair removal lasers are linked with true and questionable KPs such as vasculitis while resurfacing lasers were found to be more connected with ESA occurrence. Secondly, the laser target is significant, with vascular laser application for port-wine stains tending to result in eczematous reactions, while hair follicle destruction can frequently lead to true KPs. Thirdly, the number of sessions matters; true KPs and eruptive squamous atypia questionable KPs typically appear after one to two sessions, whereas eczematous reactions require more sessions (at least four). Additionally, skin phototype is crucial, with darker phototypes showing a higher KP frequency as laser treatment for hypertrichosis relies on melanin absorption in the hair bulge or bulb for follicle destruction, as chromophore competes with the abundant melanin in the epidermis. Further research with larger-scale studies into trauma-specific Koebner reactions is vital for refining treatment protocols, minimizing post-laser adverse effects, and improving dermatological care outcomes. [ABSTRACT FROM AUTHOR]

Hair loss is a common yet difficult to treat and distressing condition that is often seen in female patients. Causes include autoimmune, nutritional, infectious, hormonal, and traumatic etiologies. If left untreated, permanent hair loss can result due to damage to the hair follicle from long-standing inflammation. This article reviews common causes of hair loss in female patients and approaches to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Androgenetic alopecia (AGA) is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment, leading to cell apoptosis and eventual loss of hair follicles (HFs). Traditional therapeutic formulations, such as Minoxidil (MXD) tincture, have limitations in reshaping the perifollicular microenvironment and exhibit limited effectiveness. Here, we report a multi-synergistic therapeutic platform for high-performance hair regeneration therapy. The platform combines microneedle (MN) patches loaded with MXD-encapsulated nanostructured lipid carriers (MXD-NLC-MNs) and cold atmospheric plasma (CAP). The MNs' mechanical strength enables efficient transdermal delivery of MXD to the targeted dermal papilla cells, promoting cell proliferation. Furthermore, in collaboration with MXD, the mechanical stimulation exerted by MN application synergistically upregulates the expression of vascular endothelial growth factor, leading to neoangiogenesis. Meanwhile, the transient microchannels in the skin created by MNs facilitate the transdermal delivery of CAP-generated nitric oxide (NO) to the sites of HF lesions, whereby the synergistic interaction between MXD and NO boosts perifollicular vasodilation. Consequently, the perifollicular microenvironment can be effectively reshaped to accelerate hair regeneration in AGA murine models. This multi-synergistic combination therapy strategy would hold great promise for effectively treating AGA and promoting hair regrowth. [ABSTRACT FROM AUTHOR]

Chronic inflammation and excessive reactive oxygen species (ROS) can impair diabetic wound healing. Regulatory T cells (Tregs) have emerged as a promising target to promote wound healing by regulating the immune system and supporting tissue repair through the secretion of growth factors and cytokines. However, an effective strategy for the on‐demand recruitment of Tregs for wound healing is still lacking. Here, an ROS‐scavenging Tregs‐recruiting hydrogel patch is developed for the sequential release of C─C motif chemokine 22 (CCL22) triggered by the ROS in the diabetic wound bed. The hydrogel patch is prepared by crosslinking the gelatin with ROS cleavable linker together with CCL22 (RSG‐CCL22). RSG‐CCL22 presented desirable physical properties suitable for skin regeneration purposes. In addition, the ROS scavenging feature of the RSG suppresses the differentiation of T helper 17 (Th17) cells and protects the recruited Tregs from apoptosis and oxidative stress, which maximizes their function in accelerating wound closure and promoting hair follicle regeneration in a diabetic full‐thickness skin defect mouse model. Therefore, the proposed approach provides a new therapeutic strategy for tissue regeneration and wound repair via effective recruitment of functional Tregs through ROS‐triggered on‐demand delivery. [ABSTRACT FROM AUTHOR]

1. The aim of this study was to estimate heritability and genetic correlations, first among behavioural responses of juvenile South African Black ostriches towards humans and secondly with slaughter weight and skin traits.2. Behavioural traits, such as willingness of the birds to approach humans, keeping a distance from the human observer and allowing touch interactions by a human were recorded (n = 1012 birds). In addition, slaughter weight, skin size, scores for nodule size, nodule shape and the presence of hair follicles were recorded.3. Single- and multi-trait animal model analyses performed on the data using ASReml4 revealed high heritability estimates of 0.44 for allowing touch interactions and 0.48 for both willingness to approach and keeping a distance from the human observer. In addition, significant genetic correlations among behavioural response traits were estimated, ranging from −0.99 between keeping a distance and willingness to approach the human observer, to 0.87 between allowing touch interactions and willingness to approach the human observer.4. In contrast, genetic correlations of behavioural response traits with most slaughter and skin traits were low, variable, and not significant. The exception was hair follicle score, which appeared to be unfavourably correlated with key behavioural traits.5. This study suggested that the temperament of ostriches could be improved by selection of birds that demonstrate willingness to associate with humans without compromising slaughter weight or skin traits. [ABSTRACT FROM AUTHOR]

Background. Lichen planopilaris is the leading cause of cicatricial alopecia, and its management is challenging for dermatologists. It is a cell‐mediated autoimmune disorder in which activated T‐lymphocytes attack hair follicles. Aim. To compare the efficacy and safety of methotrexate versus azathioprine, two medications that affect lymphocyte function, in treating LPP. Methods. 32 LPP patients were randomly assigned to receive either 15 mg/week methotrexate or 2 mg/kg azathioprine for six months. Treatment efficacy was evaluated using the Lichen Planopilaris Activity Index (LPPAI), trichoscopy, and photography after 2, 4, and 6 months of treatment. Results. Both methotrexate and azathioprine groups showed significant improvements in LPPAI (P < 0.001) and perifollicular scaling on trichoscopy (P < 0.01). However, the two groups had no significant difference during the study. The azathioprine group significantly improved perifollicular erythema on trichoscopy (P = 0.002), but this was not significantly different from the methotrexate group (P = 0.69). Photographic assessment showed that more than 75% of patients in both groups improved without significant differences between the two groups. Conclusion. Methotrexate and azathioprine are two antilymphocyte medications which are both equally effective and well‐tolerated for managing LPP. This trial is registered with IRCT20191006045005N2. [ABSTRACT FROM AUTHOR]

Unravelling how energy metabolism and stress responses are regulated in human scalp hair follicles could reveal novel insights into the controls of hair growth and provide new targets to manage hair loss disorders. The Mitochondrial Pyruvate Carrier (MPC) imports pyruvate, produced via glycolysis, into the mitochondria, fuelling the TCA cycle. Previous work has shown that MPC inhibition promotes lactate generation, which activates murine epithelial hair follicle stem cells (eHFSCs). However, by pharmacologically targeting the MPC in short-term human hair follicle ex vivo organ culture experiments using UK-5099, we induced metabolic stress-responsive proliferative arrest throughout the human hair follicle epithelium, including within Keratin 15+ eHFSCs. Through transcriptomics, MPC inhibition was shown to promote a gene expression signature indicative of disrupted FGF, IGF, TGFβ and WNT signalling, mitochondrial dysfunction, and activation of the integrated stress response (ISR), which can arrest cell cycle progression. The ISR, mediated by the transcription factor ATF4, is activated by stressors including amino acid deprivation and ER stress, consistent with MPC inhibition within our model. Using RNAScope, we confirmed the upregulation of both ATF4 and the highly upregulated ATF4-target gene ADM2 on human hair follicle tissue sections in situ. Moreover, treatment with the ISR inhibitor ISRIB attenuated both the upregulation of ADM2 and the proliferative block imposed via MPC inhibition. Together, this work reveals how the human hair follicle, as a complex and metabolically active human tissue system, can dynamically adapt to metabolic stress. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%-90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson's trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%-90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established. [ABSTRACT FROM AUTHOR]

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development. [ABSTRACT FROM AUTHOR]

The advent of induced pluripotent stem cell (iPSC) technology has brought about transformative advancements in regenerative medicine, offering novel avenues for disease modeling, drug testing, and cell-based therapies. Patient-specific iPSC-based treatments hold the promise of mitigating immune rejection risks. However, the intricacies and costs of producing autologous therapies present commercial challenges. The hair follicle is a multi-germ layered versatile cell source that can be harvested at any age. It is a rich source of keratinocytes, fibroblasts, multipotent stromal cells, and the newly defined Hair Follicle-Associated Pluripotent Stem Cells (HAP). It can also be obtained non-invasively and transported via regular mail channels, making it the ideal starting material for an autologous biobank. In this study, cryopreserved hair follicle-derived iPSC lines (HF-iPS) were established through integration-free vectors, encompassing a diverse cohort. These genetically stable lines exhibited robust expression of pluripotency markers, and showcased tri-lineage differentiation potential. The HF-iPSCs effectively differentiated into double-positive cKIT+/CXCR4+ definitive endoderm cells and NKX6.1+/PDX1+ pancreatic progenitor cells, affirming their pluripotent attributes. We anticipate that the use of plucked hair follicles as an accessible, non-invasive cell source to obtain patient cells, in conjunction with the use of episomal vectors for reprogramming, will improve the future generation of clinically applicable pancreatic progenitor cells for the treatment of Type I Diabetes. [ABSTRACT FROM AUTHOR]

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment. [ABSTRACT FROM AUTHOR]

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination. Author summary: During embryonic development, teeth, hair follicles, and glands are examples of ectodermally-derived organs that are formed from slightly thickened epithelial layers, called placodes. These placodes undergo remarkable morphological transformations to first invaginate as an epithelial bud and later morph into a more complex structure resembling the adult organ. Movement and rearrangement of epithelial cells are thought to drive tooth invagination. But there remain key knowledge gaps in our understanding of the underlying molecular mechanisms and signaling regulation that control cell movement and epithelial morphogenesis. Here, we use the developing mouse tooth as a model to show that Shh, a signaling molecule from the early tooth signaling center, plays an important role in activating the motor protein non-muscle myosin II in dental epithelial cells. Myosin II is in turn required to promote strong adhesion between cells and power dental epithelial cells to converge towards the midline of the tooth bud to drive tooth invagination. Our results thus define the in vivo function of myosin II during epithelial invagination and explain how signaling from secreted molecules can facilitate morphogenetic cell movements via myosin II. [ABSTRACT FROM AUTHOR]

Background: The Qinghai Tibetan sheep, a local breed renowned for its long hair, has experienced significant deterioration in wool characteristics due to the absence of systematic breeding practices. Therefore, it is imperative to investigate the molecular mechanisms underlying follicle development in order to genetically enhance wool-related traits and safeguard the sustainable utilization of valuable germplasm resources. However, our understanding of the regulatory roles played by coding and non-coding RNAs in hair follicle development remains largely elusive. Results: A total of 20,874 mRNAs, 25,831 circRNAs, 4087 lncRNAs, and 794 miRNAs were annotated. Among them, we identified 58 DE lncRNAs, 325 DE circRNAs, 924 DE mRNAs, and 228 DE miRNAs during the development of medullary primary hair follicle development. GO and KEGG functional enrichment analyses revealed that the JAK-STAT, TGF-β, Hedgehog, PPAR, cGMP-PKG signaling pathway play crucial roles in regulating fibroblast and epithelial development during skin and hair follicle induction. Furthermore, the interactive network analysis additionally identified several crucial mRNA, circRNA, and lncRNA molecules associated with the process of primary hair follicle development. Ultimately, by investigating DEmir's role in the ceRNA regulatory network mechanism, we identified 113 circRNA–miRNA pairs and 14 miRNA–mRNA pairs, including IGF2BP1-miR-23-x-novel-circ-01998-MSTRG.7111.3, DPT-miR-370-y-novel-circ-005802-MSTRG.14857.1 and TSPEAR-oar-miR-370-3p-novel-circ-005802- MSTRG.10527.1. Conclusions: Our study offers novel insights into the distinct expression patterns of various transcription types during hair follicle morphogenesis, establishing a solid foundation for unraveling the molecular mechanisms that drive hair development and providing a scientific basis for selectively breeding desirable wool-related traits in this specific breed. [ABSTRACT FROM AUTHOR]

As an invaluable Chinese sheep germplasm resource, Hu sheep are renowned for their high fertility and beautiful wavy lambskins. Their distinctive characteristics have evolved over time through a combination of artificial and natural selection. Identifying selection signatures in Hu sheep can provide a straightforward insight into the mechanism of selection and further uncover the candidate genes associated with breed‐specific traits subject to selection. Here, we conducted whole‐genome resequencing on 206 Hu sheep individuals, each with an approximate 6‐fold depth of coverage. And then we employed three complementary approaches, including composite likelihood ratio, integrated haplotype homozygosity score and the detection of runs of homozygosity, to detect selection signatures. In total, 10 candidate genomic regions displaying selection signatures were simultaneously identified by multiple methods, spanning 88.54 Mb. After annotating, these genomic regions harbored collectively 92 unique genes. Interestingly, 32 candidate genes associated with reproduction were distributed in nine genomic regions detected. Out of them, two stood out as star candidates: BMPR1B and GNRH2, both of which have documented associations with fertility, and a HOXA gene cluster (HOXA1‐5, HOXA9, HOXA10, HOXA11 and HOXA13) had also been linked to fertility. Additionally, we identified other genes that are related to hair follicle development (LAMTOR3, EEF1A2), ear size (HOXA1, KCNQ2), fat tail formation (HOXA10, HOXA11), growth and development (FAF1, CCNDBP1, GJB2, GJA3), fat deposition (ACOXL, JAZF1, HOXA3, HOXA4, HOXA5, EBF4), immune (UBR1, FASTKD5) and feed intake (DAPP1, RNF17, NPBWR2). Our results offer novel insights into the genetic mechanisms underlying the selection of breed‐specific traits in Hu sheep and provide a reference for sheep genetic improvement programs. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced alopecia (CIA) represents one of the most severe side effects of chemotherapy, which forces some patients to reject cancer treatment. The exact pathophysiological mechanisms of CIA are not clearly understood, which makes it difficult to discover efficient preventive or therapeutic procedures for this adverse effect. N-acetylcysteine (NAC) has a strong antioxidant activity as it stimulates glutathione synthesis and acts as an oxygen radical scavenger. The current study tried to investigate the efficacy of NAC in preserving biochemical parameters and hair follicle structure against cyclophosphamide (CYP) administration. In total, 40 adult female C57BL/6 mice were induced to enter anagen by depilation (day 0) and divided into four groups: group I (control), group II (CYP) received a single dose of CYP [150 mg/kg body weight (B.W.)/intraperitoneal injection (IP)] at day 9, group III (CYP & NAC) received a single dose of CYP at day 9 as well as NAC (500 mg/kg B.W./day/IP) from day 6–16, and group IV (NAC) received NAC from day 6–16. CYP administration in group II induced an increase in malondialdehyde (MDA), decrease in superoxide dismutase (SOD), histological hair follicle dystrophy, disruption of follicular melanogenesis, overexpression of p53, and loss of ki67 immunoreactivity. NAC coadministration in group III reversed CYP-induced alterations in the biochemical parameters and preserved hair follicle structure, typical follicular melanin distribution as well as normal pattern of p53 and ki67 expression. These findings indicated that NAC could be used as an efficient and safe therapeutic option for hair loss induced by chemotherapy. [ABSTRACT FROM AUTHOR]

Cutaneous-type adnexal tumors involving the breast are rare and create a diagnostic dilemma as they are often indistinguishable from primary mammary neoplasms. Tumors showing hair follicular differentiation are particularly challenging due to their rarity and the subtle appreciation of the intricate microanatomy of the hair follicle. We report a triple negative cutaneous-type adnexal carcinoma with follicular differentiation involving the breast to bring attention to the existence of these specialized group of tumors which should be managed differently from conventional triple negative carcinomas of the breast. [ABSTRACT FROM AUTHOR]

Simple Summary: Dermal papilla cells (DPCs) play a key role in the growth and development of hair follicles, and their number can regulate the shape and size of hair. Previous studies found that the BMP7 gene is differentially expressed in Hu sheep lamb skin of different pattern types and plays a key role in the proliferation of Hu sheep DPCs. However, the molecular mechanism of the differential expression of the BMP7 gene remains unclear. Here, we aim to investigate the cause of the BMP7 gene differentially expressed in Hu sheep lamb skin of different pattern types. Our findings demonstrate that DNA methylation modification can affect the expression of the BMP7 gene and can regulate the proliferation and cell cycle of Hu sheep DPCs. Previous studies have shown that the BMP7 gene is differentially expressed in Hu sheep lamb skin of different pattern types, and its expression level is significantly correlated with hair follicle indices of different pattern types, but the molecular mechanism of the differential expression of the BMP7 gene remains unclear. This study investigated the effect of DNA methylation on the transcriptional expression of BMP7. Firstly, we found that the mRNA expression of the BMP7 gene and the activity of the core promoter of the BMP7 gene were upregulated after 5-Aza-Deoxycytidine-induced demethylation treatment using qRT-PCR and double luciferase reporter assay. Then, we found that the proliferation of Hu sheep DPCs in vitro was promoted after 5-Aza-Deoxycytidine-induced demethylation treatment through qRT-PCR, CCK-8, and EdU assay, and that the overexpression of DNMT1 in DPCs induced the opposite effect. In addition, the results of the cell cycle assay reveal that the percentage of cells in the S phase was increased after 5-Aza-Deoxycytidine-induced demethylation treatment, and that the percentage of cells in the S phase was decreased after overexpression of DNMT1 in DPCs. This study indicated that the differential expression of the BMP7 gene in different patterns of Hu sheep lamb skin may be regulated by DNA methylation modification. In addition, DNA methylation can regulate the proliferation and cell cycle of DPCs in Hu sheep. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are known for their immunosuppressive properties. Based on the demonstrated anti-inflammatory effect of mouse MSCs from hair follicles (moMSCORS) in a murine wound closure model, this study evaluates their potential for preventing type 1 diabetes (T1D) in C57BL/6 mice. T1D was induced in C57BL/6 mice by repeated low doses of streptozotocin. moMSCORS were injected intravenously on weekly basis. moMSCORS reduced T1D incidence, the insulitis stage, and preserved insulin production in treated animals. moMSCORS primarily exerted immunomodulatory effects by inhibiting CD4+ T cell proliferation and activation. Ex vivo analysis indicated that moMSCORS modified the cellular immune profile within pancreatic lymph nodes and pancreatic infiltrates by reducing the numbers of M1 pro-inflammatory macrophages and T helper 17 cells and upscaling the immunosuppressive T regulatory cells. The proportion of pathogenic insulin-specific CD4+ T cells was down-scaled in the lymph nodes, likely via soluble factors. The moMSCORS detected in the pancreatic infiltrates of treated mice presumably exerted the observed suppressive effect on CD4+ through direct contact. moMSCORS alleviated T1D symptoms in the mouse, qualifying as a candidate for therapeutic products by multiple advantages: non-invasive sampling by epilation, easy access, permanent availability, scalability, and benefits of auto-transplantation. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 5 (FGF5) plays key roles in promoting the transition from the anagen to catagen during the hair follicle cycle. The sheep serves as an excellent model for studying hair growth and is frequently utilized in various research processes related to human skin diseases. We used the CRISPR/Cas9 system to generate four FGF5-edited Dorper sheep and only low levels of FGF5 were detected in the edited sheep. The density of fine wool in GE sheep was markedly increased, and the proportion of fine wool with a diameter of 14.4–20.0 μm was significantly higher. The proliferation signal in the skin of gene-edited (GE) sheep was stronger than in wild-type (WT) sheep. FGF5 editing decreased cortisol concentration in the skin, further activated the activity of antioxidant enzymes such as Glutathione peroxidase (GSH-Px), and regulated the expression of Wnt signaling pathways containing Wnt agonists (Rspondins, Rspos) and antagonists (Notum) in hair regeneration. We suggest that FGF5 not only mediates the activation of antioxidant pathways by cortisol, which constitutes a highly coordinated microenvironment in hair follicle cells, but also influences key signals of the Wnt pathway to regulate secondary hair follicle (SHF) development. Overall, our findings here demonstrate that FGF5 plays a significant role in regulating SHF growth in sheep and potentially serves as a molecular marker of fine wool growth in sheep breeding. [ABSTRACT FROM AUTHOR]

• The nipple-areolar complex (NAC) is a major landmark anatomically and when performing breast ultrasound. • However, the nipples themselves do not seem to be closely observed unless there are any special symptoms or changes in the shape of the nipple. • It is also not easy to view the protruding nipple as a linear ultrasound probe. • Therefore, we aim to help in diagnosis by introducing examination methods that allow for good observation of the nipple area with ultrasound and the characteristics of ultrasound images for each disease in the NAC. • In addition, ultrasound-guided aspiration or biopsy may be helpful for accurate diagnosis, including exclusion of malignancy, and determination of treatment method. Categories of nipple-areolar complex (NAC) lesions 1. Anatomy and variation 2. Tips for ultrasonographic evaluation of the nipple 3. Benign conditions 4. Malignant conditions 1. Anatomy And Variation 3) Montgomery glands and tubercles Montgomery glands (areolar glands) • sebaceous glands in the areola • make oily secretions (lipoid fluid) to keep the areola and the nipple lubricated and protected • The portions of the gland visible on the skin's surface (1–2-mm-diameter) • The round bumps are found in the areola, and on the nipple itself. • They can become exposed and raised when the nipple is stimulated. • The skin over the surface opening is lubricated and tends to be smoother than the rest of the areola. • The tubercles become more pronounced during pregnancy. 4) Polythelia (accessory nipples) • most commonly in the axilla or inframammary fold • may occur anywhere along the embryologic milk line, from the axilla to the groin • pigmented accessory nipples may be mistaken for moles • Polythelia is uncommon, also may be seen in males Polymastia (Supernumerary breasts; formation of an accessory true mammary gland) also may occur when involution of the milk line is incomplete, but it is rare. Accessory breasts may have normal tissue and even function during lactation. 5) Nipple retraction or inversion • Nipple inversion should only be used when the entire nipple is pulled inward, whereas retraction should be used when the nipple only has an inward slit like area. • Nipple retraction and inversion are either congenital or acquired and either unilateral or bilateral. Nipple inversion • typically occur during puberty • normal variants of the nipple position or result from the development of fibrous tissue between the nipple and the subareolar parenchyma • hinders breast-feeding and predisposes to mastitis and abscess formation • when inverted nipples are detected on mammography, radiologists must not confuse them with subareolar masses Grade 1 Inverted nipple is easily pulled out maintains its projection fairly well without traction Grade 2 Inverted nipple can be pulled out, but not as easily after releasing traction, the nipple tends to fall back and invert again. Grade 3 Nipple is severely retracted and inverted difficult to physically force this nipple out and hold it there. 2. Tips for ultrasonographic evaluation of the nipple 1) Clinical examination; symptoms, inspection 2) Bilateral assessment 3) Linear & high frequency transducer (17–5-MHz) 4) Using a generous amount of jelly around the nipple 5) Intraductal lesion evaluation with radial scan 6) Doppler mode increase the specificity of conventional B-mode US and improve its diagnostic performance 3. Benign conditions 1) Dermal lesions 2) Subareolar abscess 3) Papillomas 4) Benign masses with calcifications • Eczema of the nipple-areolar complex typically occurs bilaterally and may be associated with systemic symptoms of atopic dermatitis, including (but not limited to) flexural dermatitis. Eczema is responsive to topical application of a moderate-dose steroid cream. However, if the symptoms do not improve, a biopsy may be necessary to exclude Paget disease of the nipple, which may have a similar appearance. • Psoriasis also may cause nipple changes, including excoriation and ulceration. A complete clinical history may be helpful for differential diagnosis, as patients may have other manifestations of disease. • Nevoid hyperkeratosis, a benign idiopathic condition that is characterized by slowly growing verrucous thickening and hyperpigmentation of the nipple, areola, or both; and periareolar fistula, an extraintestinal cutaneous manifestation of Crohn disease. • Pathogenesis • -Epidermalization or squamous metaplasia of the cuboidal epithelium lining the ducts -Leading to obstruction of the ducts by keratin plugs -Dilatation of the duct and ampulla occurs -Rupture of the thin columnar epithelial lining of the major duct formation of an abscess • MG: Negative in young patients with dense breast parenchyma • US: Most common imaging option for detecting abscess • Ill-defined or a well-defined outline • Anechoic or low echoic lesion with posterior enhancement • Treatment; Abscess drainage, Surgical therapy (warranted) Central papillomas • arise in the subareolar space and are usually solitary, within major ducts • spontaneous, unilateral, bloody nipple discharge • intraductal proliferation of epithelial and myoepithelial cells overlying a fibro-vascular stalk • less associated with a coexisting malignancy • US findings; mass, a complex cystic-solid mass or duct changes only ; internal vascularity • Calcifications may develop in the nipple areolar complex in some patients and typically are benign. • Calcifications may occur in the skin of the areola, within the Montgomery glands, within hair follicles, in association with a mass, or in the context of Paget disease. • Calcifications in the skin of the areola may be secondary to surgery such as reduction mammoplasty but also may occur in patients without a history of such surgery. • Calcified cutaneous horns are typically asymptomatic and benign but also have been associated with malignant lesions, including Paget disease and squamous cell carcinoma. 1) Paget disease 2) Invasion and recurrence of carcinoma • Malignant masses of the nipple-areolar complex may be more difficult to diagnose than cancers elsewhere in the breast because subareolar masses can be easily confused with normal nipple structures on mammography. • On sonography, subareolar masses or intraductal lesions may be more easily identified than on mammography. • Contrast- enhanced MRI is useful when mammographic and sonographic findings are inconclusive. • Underlying cancer may originate immediately deep to the nipple or extend from another location in the breast to the nipple-areolar complex. • Nipple retraction and ulceration are secondary signs of malignancy and may occur with the extension of advanced breast cancer to the skin surface. • a rare disorder of the nipple-areolar complex • 0.5% to 5% of all breast cancer (often associated with an underlying in situ or invasive carcinoma) • Infiltration of the nipple epidermis by adenocarcinoma cells - characteristic eczematous eruption on the nipple and areola. • Clinical features - Early; erythema and scaling of the nipple, eczematiod change - Late; nipple erosion or ulceration, bloody nipple discharge, nipple retraction - palpable mass(50%) or thickening in the breast • Histologic hallmark of Paget disease - involvement of the epidermis by malignant cells called Paget cells • MG - skin thickening, nipple retraction, subareolar or more diffuse malignant microcalcifications - discrete mass or masses - negative (50%) • US - parenchymal heterogeneousness, hypoechoic areas, discrete masses, skin thickening or dilated ducts • MRI - abnormal nipple enhancement, thickening of the nipple-areolar complex - linear clumped enhancement indicative of DCIS in association with Paget disease [ABSTRACT FROM AUTHOR]

The native Spanish Merino breed was the founder of all the other Merino and Merino-derived breeds worldwide. Despite the fact that this breed was created and improved to produce the highest quality fine wool, the global wool market crisis led to the wholescale crossing of most of the herds with breeds for meat purposes. Nevertheless, there are still some purebred animals with a high potential for producing quality wool. The objective of this study was to characterize the current wool quality of the breed and identify genes associated with these parameters. To achieve this, over 12,800 records from the most representative animals of the breed (registered in the herd book) were analyzed using the Australian OFDA 2000 system, for parameters such as fiber diameter (FD), standard deviation (SD), coefficient of variation (CV), fibers over 15 microns (>15%), staple length (SL), and comfort factor (CRV). Additionally, animals with the most extreme FD values were whole-genome sequenced using NGS. Genome-wide association studies (GWAS) determined the association of 74 variants with the different traits studied, which were located in 70 different genes. Of these genes, EDN2, COL18A1, and LRP1B, associated with fibers over 15%, and FGF12 and ADAM17, associated with SL, play a key role in hair follicle growth and development. Our study reveals the great potential for recovering this breed for fine wool production, and identifies five candidate genes whose understanding may aid in that selection process. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to investigate the mechanism by which low‐level laser stimulation promotes the proliferation of intraepithelial hair follicle stem cells (HFSCs) in wounds. This research aims to expand the applications of laser treatment, enhance wound repair methods, and establish a theoretical and experimental foundation for achieving accelerated wound healing. Methods: The experimental approach involved irradiating a cell model with low‐level laser to assess the proliferation of HFSCs and examine alterations in the expression of proteins related to the Wnt/β‐catenin signaling pathway. A mouse back wound model was established to investigate the effects of low‐level laser irradiation on wound healing rate, wound microenvironment, and the proliferation of HFSCs in relation to the Wnt/β‐catenin signaling pathway. Results: The research findings indicate that low‐level laser light effectively activates the Wnt signaling pathway, leading to the increased accumulation of core protein β‐catenin and the upregulation of key downstream gene Lef 1. Consequently, this regulatory mechanism facilitates various downstream biological effects, including the notable promotion of HFSC proliferation and differentiation into skin appendages and epithelial tissues. As a result, the process of wound healing is significantly accelerated. Conclusion: Low levels of laser activates the Wnt signalling pathway, promotes the regeneration of hair follicle stem cells and accelerates wound healing. [ABSTRACT FROM AUTHOR]

Transglutaminases (TGMs) cross-link proteins by introducing covalent bonds between glutamine and lysine residues. These cross-links are essential for epithelial cornification which enables tetrapods to live on land. Here, we investigated which evolutionary adaptations of vertebrates were associated with specific changes in the family of TGM genes. We determined the catalog of TGMs in the main clades of vertebrates, performed a comprehensive phylogenetic analysis of TGMs, and localized the distribution of selected TGMs in tissues. Our data suggest that TGM1 is the phylogenetically oldest epithelial TGM, with orthologs being expressed in the cornified teeth of the lamprey, a basal vertebrate. Gene duplications led to the origin of TGM10 in stem vertebrates, the origin of TGM2 in jawed vertebrates, and an increasing number of epithelium-associated TGM genes in the lineage leading to terrestrial vertebrates. TGM9 is expressed in the epithelial egg tooth, and its evolutionary origin in stem amniotes coincided with the evolution of embryonic development in eggs that are surrounded by a protective shell. Conversely, viviparous mammals have lost both the epithelial egg tooth and TGM9. TGM3 and TGM6 evolved as regulators of cornification in hair follicles and underwent pseudogenization upon the evolutionary loss of hair in cetaceans. Taken together, this study reveals the gain and loss of vertebrate TGM genes in association with the evolution of cornified skin appendages and suggests an important role of TGM9 in the evolution of amniotes. [ABSTRACT FROM AUTHOR]

Melanin is considered the main chromophore for laser hair removal. Due to a lack of laser-absorbing chromophores, removing non-pigmented hair with laser is quite problematic with unsatisfactory outcomes. This problem could be solved by delivering more melanin to the area around the hair follicle and enhancing that area as a target for light absorption. The insolubility of Sepia melanin as an exogenous dye, in most solvents, limits its bioavailability and thus its clinical use. In our study, to overcome the solubility problems and increase the bioavailability of melanin for biomedical and cosmetic applications, natural sepia melanin was loaded in different nano-delivery systems (spanlastics and transfersomes) to be delivered to the hair follicles. The different formulations of melanin were prepared and characterized. In vivo skin deposition and histopathological studies were conducted on albino mice. Transmission electron microscopy (TEM) showed the spherical shape of the prepared vesicles with an average particle size of 252 and 262 nm and zeta potential of −22.5 and −35 mV for melanin spanlastics and melanin transfersomes, respectively. Histopathological examination of hair follicles and pilosebaceous glands for the irradiated and non-irradiated albino mice skin was studied post the application of the prepared formulations topically and subcutaneously. Qualitative statistical analysis was conducted and melanin transfersomes and melanin spanlastics showed significant damage to pilosebaceous glands and hair follicles with a p-value of 0.031 and 0.009 respectively. Melanin nanovesicles as transfersomes and spanlastics could be considered a promising approach for the removal of non-pigmented hair. [ABSTRACT FROM AUTHOR]

Ovarian dermoid cyst is characterised by the presence of hair follicles, sebaceous glands grossly observed as clusters of matted hair in greyish cheesy material in the vicinity of ovaries. Upon examination of 235 buffalo genitalia, five were found to have abnormal ovarian texture and were relatively large in size. Further investigation revealed presence of dermoid cyst in these ovaries. Histopathological analysis showed degenerated primary, secondary and tertiary/Graafian follicles in the ovarian parenchyma, with patches of neuro‐ectodermal rosette‐like structures composed of glial cells. Other extra‐gonadal tissues often less organised were also observed like cartilage, fibrous connective tissue and glandular structures. In two of the specimens, corpus luteum with degenerated luteal cells was also present in the parenchyma of the ovary. These detailed investigations pointed to the infertility problems in buffaloes associated with this condition and often dictated in slaughterhouse‐derived ovaries. It has clinical significance as these structures are often confused with cystic ovarian disease upon rectal palpation, and treatment is unsuccessful in reducing the size of the ovary at the field level. [ABSTRACT FROM AUTHOR]

Chemotherapy induced alopecia (CIA) is one of the most common side effects in cancer patients, however; it doesn't have an effective pharmacological treatment yet. In this study we aimed to research the protective effect of newly developed HDDPiW-jSB solution on docetaxel (DTX) -induced rat alopecia model. Docetaxel (10 mg/kg/week) was administered to the 6–8 months old rats for three weeks. HDDPiW-jSB solution was applied once or twice a week for 4 weeks beginning prior to one week before DTX. Rat hair follicles were evaluated with hematoxylin-eosin and immune-histochemical staining. In the first stage of this study, alopecia was successfully developed by DTX (10 mg/kg/three times) application. In the second stage of the study, application of HDDPiW-jSB solution, did not change the study parameters significantly on control group. The solution improved the anagen hair follicle count and Bcl-2 levels in the skin samples of DTX-induced alopecic rat groups, especially when applied twice weekly. Additionally, level of Caspase 3 was decreased. HDDPiW-jSB solution was safe when applied on the skin. Topical HDDPiW-jSB solution could be effective and safe for the protection of DTX-induced alopecia in rat models. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 12-year-old boy with alopecia universalis and trachyonychia, a nail disorder associated with alopecia areata. The patient showed improvement in trachyonychia after treatment with diphenylcyclopropenone (DPCP) for alopecia universalis. The study highlights the relationship between trachyonychia and alopecia areata, as well as the potential systemic therapeutic effects of contact immunotherapy. Dermoscopy was used to monitor the response to treatment, showing promise as a diagnostic and assessment tool for trachyonychia therapies. [Extracted from the article]

Background: Tinea versicolor is a very common condition. We reported a specific follicular manifestation and proposed that this particular presentation might be related to the patient's history of previous keratosis pilaris. Case presentation: A 46-year-old Asian woman of Han ethnicity presented to the clinic with trunk lesions for over a year. On physical examination: multiple light brown patches of varying size centered on hair follicles in the axillae and trunk, with the patches on the back fusing together and scales visible on the surface of the patches. Finally, through fungal microscopy and pathological examination, the patient was diagnosed with folliculocentric tinea versicolor. Conclusions: Follicular tinea versicolor is a rare type of tinea versicolor. It is still not clear what causes tinea versicolor to become folliculocentric. This case may suggest that patients with a history of keratosis pilaris may have a tendency to develop follicular centration in the course of other diseases. [ABSTRACT FROM AUTHOR]

Malignant Proliferating Trichilemmal Tumour (MPTT) is a rare, malignant cutaneous adnexal tumour that originates from the outer root sheath cells of the isthmus of hair follicles. This article aims to report a rare case of a high-grade malignant trichilemmal tumour arising in the context of a proliferating Trichilemmal Cyst (TC) in a 65-year-old female who presented with a painless swelling in the left gluteal region that had been present for two months. There have been only about 100 cases reported so far. Both the clinical features and the imaging findings were suggestive of an ostensibly benign lesion. As a result, the cyst was excised; however, further histopathological evaluation revealed an unexpected case of rare MPTT. Consequently, a timely second revision surgery was performed to ensure tumour-free margins. This case illustrates that the diagnosis of MPTT is highly challenging. Without prior knowledge and a high index of suspicion, the diagnosis of MPTT could easily be missed. MPTT is often misdiagnosed as a variant of Squamous Cell Carcinoma (SCC). The subtle nuances of the unique histopathological pattern of MPTT can help differentiate it from SCC. [ABSTRACT FROM AUTHOR]

This article discusses the use of trichoscopy as a monitoring tool in assessing treatment response in scalp pemphigus (SP), an autoimmune blistering disease. The study conducted at the University of Bologna enrolled 37 adult patients with confirmed SP and assessed their clinical status using the Pemphigus Disease Area Index (PDAI), laboratory evaluations, and trichoscopy. The results showed that trichoscopy can be valuable in diagnosing and monitoring SP, with dystrophic hair disappearance indicating treatment efficacy. The study also found a correlation between anti-Dsg values and trichoscopy, suggesting that anagen hair loss is related to disease activity. Trichoscopy can serve as a non-invasive tool for monitoring SP and may eliminate the need for skin biopsy. However, the study has limitations, and further research is needed to investigate persistent trichoscopic signs and recurrences. [Extracted from the article]

This article discusses the use of single microneedle radiofrequency (SMRF) therapy as a potential treatment for dissecting cellulitis of the scalp (DCS), a rare inflammatory condition that can cause permanent hair loss. The usual treatment for DCS involves Isotretinoin and oral antibiotics, but the effectiveness can vary. Recent studies have shown that SMRF therapy can reduce sebum secretion and treat acne, making it a potential alternative treatment for DCS. The article presents a case study of a 16-year-old patient who experienced significant improvement in their scalp lesions after receiving isotretinoin combined with SMRF therapy. However, more research is needed to fully understand the potential of SMRF for treating DCS. [Extracted from the article]

Abstract JAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.