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Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent inflammatory lesions, which affect skin and hair follicles in intertriginous areas. HS has a multifactorial aetiology resulting in barrier dysfunction associated with aberrant immune activation. There is increased evidence for the role of inflammasomes in the pathophysiology of inflammatory skin diseases, including HS. Inflammasomes are multiprotein complexes activated following exposure to danger signals, including microbial ligands and components of damaged host cells. Inflammasome activation induces many signalling cascades and subsequent cleavage of proinflammatory cytokines – most notably interleukin (IL)-1β – which have a role in HS pathogenesis. Limited immunotherapies are approved for treating moderate-to-severe HS, with variable response rates influenced by disease heterogeneity. Inflammasomes represent attractive targets to suppress multiple inflammatory pathways in HS, including IL-1β and IL-17. This review aims to summarize the role of inflammasomes in HS and to evaluate evidence for inflammasomes as therapeutic targets for HS treatment. [ABSTRACT FROM AUTHOR]

Background Inhibitors of epidermal growth factor receptor (EGFRi) or mitogen-activated kinase (MEKi) induce a folliculitis in 75–90% of patients, the pathobiology of which remains insufficiently understood. Objectives To characterize changes in the skin immune status and global transcriptional profile of patients treated with EGFRi; to investigate whether EGFRi affects the hair follicle's (HF) immune privilege (IP); and to identify early proinflammatory signals induced by EGFRi/MEKi in human scalp HFs ex vivo. Methods Scalp biopsies were taken from patients exhibiting folliculitis treated long term with EGFRi ('chronic EGFRi' group, n = 9) vs. healthy scalp skin (n = 9) and patients prior to commencing EGFRi treatment and after 2 weeks of EGFRi therapy ('acute EGFRi' group, n = 5). Healthy organ-cultured scalp HFs were exposed to an EGFRi (erlotinib, n = 5) or a MEKi (cobimetinib, n = 5). Samples were assessed by quantitative immunohistomorphometry, RNA sequencing (RNAseq) and in situ hybridization. Results The 'chronic EGFRi' group showed CD8+ T-cell infiltration of the bulge alongside a partial collapse of the HF's IP, evidenced by upregulated major histocompatibility complex (MHC) class I, β2-microglobulin (B2 M) and MHC class II, and decreased transforming growth factor-β1 protein expression. Healthy HFs treated with EGFRi/MEKi ex vivo also showed partial HF IP collapse and increased transcription of human leucocyte antigen (HLA)-A, HLA-DR and B2 M transcripts. RNAseq analysis showed increased transcription of chemokines (CXCL1, CXCL13, CCL18, CCL3, CCL7) and interleukin (IL)-26 in biopsies from the 'chronic EGFRi' cohort, as well as increased IL-33 and decreased IL-37 expression in HF biopsies from the 'acute EGFRi' group and in organ-cultured HFs. Conclusions The data show that EGFRi/MEKi compromise the physiological IP of human scalp HFs and suggest that future clinical management of EGFRi/MEKi-induced folliculitis requires HF IP protection and inhibition of IL-33. [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]

Terminal differentiation of epithelial cells is critical for the barrier function of the skin, the growth of skin appendages, such as hair and nails, and the development of the skin of amniotes. Here, we present the hypothesis that the differentiation of cells in the embryonic periderm shares characteristic features with the differentiation of epithelial cells that support the morphogenesis of cornified skin appendages during postnatal life. The periderm prevents aberrant fusion of adjacent epithelial sites during early skin development. It is shed off when keratinocytes of the epidermis form the cornified layer, the stratum corneum. A similar role is played by epithelia that ensheath cornifying skin appendages until they disintegrate to allow the separation of the mature part of the skin appendage from the adjacent tissue. These epithelia, exemplified by the inner root sheath of hair follicles and the epithelia close to the free edge of nails or claws, are referred to as scaffolding epithelia. The periderm and scaffolding epithelia are similar with regard to their transient functions in separating tissues and the conserved expression of trichohyalin and trichohyalin-like genes in mammals and birds. Thus, we propose that parts of the peridermal differentiation program were coopted to a new postnatal function during the evolution of cornified skin appendages in amniotes. [Display omitted] • The periderm prevents adhesion of adjacent stratified epithelia during development • Cornified skin appendages require scaffolding epithelia for morphogenesis • The inner root sheath of the hair follicle is an example a scaffolding epithelium • Scaffoldin is a marker of the periderm and scaffolding epithelia of birds • Trichohyalin is the mammalian homolog of scaffoldin [ABSTRACT FROM AUTHOR]

Background: The growth of secondary hair follicles (SHFs) in cashmere goats has periodic changes, including telogen, anagen, and catagen, during which proteins play important roles as the executor of life activities. Results: In this study, the skin tissues of cashmere goats at three different growth stages of SHFs were collected for proteome sequencing and validation experiments. Through protein differential expression analysis and time series analysis, FKBP prolyl isomerase 10 (FKBP10) and fibrillin 2 (FBN2) were screened as the key proteins for SHF cycle growth of cashmere goats, and albumin (ALB), collagen type I alpha 1 chain (COL1A1) and elastin (ELN) were predicted to be their interacting proteins. The results of quantitative real-time PCR (qRT- PCR), western blot, and immunohistochemistry experiments showed that the mRNA and protein expression levels of FKBP10, FBN2, COL1A1, ELN and ALB were higher in anagen and lower in telogen. They were all highly expressed in the outer root sheath of SHFs in anagen. Conclusion: FKBP10, FBN2, COL1A1, ELN, and ALB can promote the growth of SHFs in cashmere goats. This study lays the foundation for analyzing the growth cycle regulatory mechanism of SHFs in cashmere goats, and provides new ideas for further improving cashmere yield and quality. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion To investigate the role of miR‐30a‐5p on the proliferation and apoptosis of hair follicle stem cells (HFSCs) and whether the Wnt/β‐catenin signaling pathway is involved.HFSCs derived from the vibrissa of mammary rats were obtained by enzymatic digestion, and subsequently the obtained HFSCs were treated with Lipofectamine 2000 cell transfection and divided into normal cell culture group (control), miR‐30a‐5p overexpression group (miR‐30a‐5p mimic), miR‐30a‐5p empty vector group (miR‐NC), miR‐30a‐5p inhibitor group (in‐miR‐30a‐5p), and in‐miR‐30a‐5p empty vector group (in‐miR‐NC). After transfection, the cell proliferation and apoptosis rates were examined separately. In addition, the mRNA expression of β‐catenin, proliferating cell nuclear antigen (PCNA) and apoptosis‐related genes (Bax and Bcl‐2) were examined.The results of cell proliferation ability showed that in‐miR‐30a‐5p group promoted cell proliferation of HFSCs relative to other groups, along with significant upregulation of gene levels of PCNA. Apoptosis analysis indicated that apoptosis rate was reduced in the in‐miR‐30a‐5p group, and the expression of Bax was suppressed, while that of Bcl‐2 was promoted. Wnt/β‐catenin signaling pathway investigation revealed a significant increase in the levels of β‐catenin in HFSCs in the in‐miR‐30a‐5p group.Downregulation of miR‐30a‐5p levels inhibited HFSCs apoptosis and simultaneously promoted proliferation, furthermore, the increased expression of β‐catenin indirectly confirmed the activation of the Wnt/β‐catenin signaling pathway. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objectives Methods Results Conclusions Polytrichia is a common clinical and trichoscopic feature in folliculitis decalvans (FD) that morphologically corresponds to compound follicular structures (CFS) of six or more follicles sharing a single infundibulum, surrounded by fibrosis.To characterize the type of follicles in the CFS in scalp biopsy specimens from FD.We retrospectively reviewed 10 scalp biopsy specimens obtained by using the trichoscopy‐guided approach from the affected scalp of patients diagnosed with early‐stage FD between 2018 and 2023. We assessed the number and type of follicles within the CFS on horizontal sections.The total number of assessed follicles was 205, out of which 159 were part of CFS. Of those, 156 were terminal follicles (146 anagen and ten telogen), three intermediate, and zero vellus follicles. Other common findings included dense mixed cell infiltrate consisting of histiocytes, plasma cells, lymphocytes, neutrophils, and eosinophils; psoriasiform hyperplasia; and fragmented hair shafts.We show that CFS in FD are composed largely of terminal anagen follicles. This may help with further understanding of the disease. [ABSTRACT FROM AUTHOR]

Background: Cashmere, named as "soft gold", derives from the secondary hair follicles (SHFs) of cashmere goat which is vital to Northwest China's economy. The cytodifferentiation stage (E120), mirroring the complete hair follicle (HF) structure of adult goats and marking a critical phase in SHF development. Therefore, this study aims to enhance the understanding of SHF development and its impact on fiber quality, informing breeding strategies. Results: From the scRNA-seq data analysis, the intricate processes and transcriptional dynamics of inner layer cell differentiation of HFs were unveiled in this study. we identified nine cell populations during cytodifferentiation and key structures such as the hair shaft and inner root sheath. And we discovered three main inner layer lineages and seven subpopulations, clarifying their roles in specialization and signaling. Pseudotime mapping analysis showed cell evolution from early stage to mature stages marked by unique gene expressions, and the intermediate stage on the differentiation of each lineage was revealed. The identification and spatial localization of specific transcription factors, such as GATA3, LEF1 and PRDM1, as well as keratin genes highlight regulatory pathways involved in HF development, which was further validated by immunofluorescence. These findings suggested the potential strategies to improve fiber quality, and the discovery of diverse cell types and their developmental molecular mechanisms, particularly in this species-specific context, offered a nuanced view of the regulatory mechanisms driving HF development in cashmere goats. Conclusion: Overall, these findings provide a systematic molecular atlas of skin, defining three major branches and cell states of inner layer cells of HF, and determining how the branch-specific transcription factors, keratins, and signals coordinate HF morphogenesis during cytodifferentiation stage. This research not only advances skin tissue research in goats but also holds broader implications for the understanding of HF regeneration and development across various species. [ABSTRACT FROM AUTHOR]

Oxytocin has various effects ranging from promoting labor in pregnant women to alleviating stress. Recently, we reported the hair growth-promoting effects of oxytocin in hair follicle organoids. However, its clinical application faces challenges such as rapid degradation in vivo and poor permeability due to its large molecular weight. Therefore, in this study, we investigated the effects of the oxytocin receptor (OXTR) agonists WAY267464 and LIT001 as alternatives to oxytocin on hair growth. Human dermal papilla (DP) cells were cultured in WAY267464 or LIT001-supplemented medium. The addition of WAY267464 and LIT001 increased the expression of hair growth-related genes in DP cells. We tested the hair growth-promoting effects of WAY267464 and LIT001 using hair follicle organoids in vitro and found that they significantly promoted hair follicle sprouting. Thus, our findings indicate that WAY267464 and LIT001 are potential hair growth agents and may encourage further research on the development of novel hair growth agents targeting OXTR in patients with alopecia. [ABSTRACT FROM AUTHOR]

Introduction: The hair follicle (HF) is a micro-organ capable of regeneration. A HF cycle consists of an anagen, catagen and telogen. Abnormalities in the HF cycle can lead to many hair disorders such as hair loss. The pig is a good biomedical model, but there are few data on their HF cycle. The aim of this study was to classify the pig HF cycle and determine the feasibility of the pig as an animal model for human HF cycle. Methods: Skin samples from 10 different postnatal (P) days Yorkshire pigs was collected to determine the key time points of the first HF cycle in pig by H&E staining, immunofluorescence staining, q-PCR and western-blot. Results: By morphological observation and detection of markers at different stages, pig HF cycle was classified into three main periods - the first anagen until P45, catagen (P45-P85), telogen (P85-P100), and next anagen (>P100). In addition, we examined the expression of important genes AE15, CD34, Versican, Ki67 et al. related to the HF cycle at different stages of pig HF, indicating that pig and human share similarities in morphology and marker gene expression patterns of HF cycle. Discussion: Our findings will facilitate the study of HF cycle and offer researchers a suitable model for human hair research. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterised by epidermal virus replication in skin and mucosa and the formation of blisters. We have previously shown that VZV infection has a profound effect on keratinocyte differentiation, altering the normal pattern of epidermal gene expression. In particular, VZV infection reduces expression of suprabasal keratins 1 and 10 and desmosomal proteins, disrupting epidermal structure to promote expression of a blistering phenotype. Here, we extend these findings to show that VZV infection upregulates the expression of keratin 15 (KRT15), a marker expressed by basal epidermal keratinocytes and hair follicles stem cells. We demonstrate that KRT15 is essential for VZV replication in the skin, since downregulation of KRT15 inhibits VZV replication in keratinocytes, while KRT15 exogenous overexpression supports viral replication. Importantly, our data show that VZV upregulation of KRT15 depends on the expression of the VZV immediate early gene ORF62. ORF62 is the only regulatory gene that is mutated in the live attenuated VZV vaccine and contains four of the five fixed mutations present in the VZV Oka vaccine. Our data indicate that the mutated vaccine ORF62 is not capable of upregulating KRT15, suggesting that this may contribute to the vaccine attenuation in skin. Taken together our data present a novel association between VZV and KRT15, which may open a new therapeutic window for a topical targeting of VZV replication in the skin via modulation of KRT15. [ABSTRACT FROM AUTHOR]

Hair loss is a prevalent issue worldwide, which, though not life-threatening, can result in psychological problems, low self-esteem, and social anxiety. Previous studies have shown that ultraviolet radiation can have negative effects on hair follicle cells, leading to hair loss, while the impact of blue light on hair and hair follicle has largely been overlooked. This study aimed to examine the effects of blue light on hair follicle stem cells (HFSCs) and primary dermal papilla cells (DPCs), which are essential components of hair follicles. Human HFSCs and primary DPCs were exposed to blue light (457 nm) at various intensities (1, 4, 8, and 16 mW/cm2) for 3 days. Subsequently, cell viability, cell proliferation, and intracellular reactive oxygen species (ROS) were assessed. The results showed that blue light (457 nm) significantly reduced the cell viability and proliferation of HFSCs and DPCs in vitro, with the inhibition being intensity-dependent. Additionally, blue light triggered the overproduction of ROS in the DPCs. While the exact mechanisms by which blue light affects hair follicle cells remain unclear, these findings suggest that blue light could impede the growth of these cells. This insight may offer a new approach to protecting hair by avoiding exposure to high-intensity blue light. Highlights: 457 nm blue LED light significantly inhibited the cell viability of HFSCs and DPCs. Blue light at comparable high irradiances has toxic effects on hair follicle cells. 16 mW/cm2 blue light significantly induced oxidative stress and inhibited growth of DPCs. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is an immune‐mediated chronic alopecia disease, but its specific pathogenesis is unclear. Gene expression data for AA patients (AAs) and healthy controls (HCs) were retrieved from the GEO database, and the differentially expressed genes (DEGs) between AAs and HCs were identified. Then, GO, KEGG and GSEA analysis were performed. A PPI network for the DEGs was then constructed to screen for hub genes, which were validated by three additional datasets. Subsequently, the potential miRNAs interacting with the hub genes were obtained through TarBase and miRNet. The differentially expressed lncRNAs (DElncRs) were obtained for subcellular localisation analysis, and the DElncRs located in the cytoplasm were further screened to identify miRNAs that interact with them. The shared miRNAs interacting with the hub genes and lncRNAs were used to construct a network of mRNA‐miRNA‐lncRNA interactions. Lastly, ROC analysis was performed to evaluate the potential diagnostic value of the hub genes and DElncRs identified. A total of 173 DEGs were obtained, mainly enriched in cytokines, chemokines, hair follicle development and hair cycle related signalling pathways. Through PPI screening and validation based on 3 additional datasets, 24 hub genes were finally yielded. Of them, five hub genes were upregulated and the potential miRNAs that interact with these five hub genes were identified. Additionally, 26 DElncRs were obtained, including 9 upregulated lncRNAs located in the cytoplasm that were predicted to interact with the miRNAs. Finally, an mRNA‐miRNA‐lncRNA regulatory network was constructed using five hub genes, four lncRNAs and their shared five miRNAs. The regulatory relationship between CD8A, mir‐185‐5p and FOXD2‐AS1 might be crucial in AA pathogenesis, with CD8A and FOXD2‐AS1 exhibiting diagnostic potential. CD8A and FOXD2‐AS1 may serve as potential therapeutic targets in AA. [ABSTRACT FROM AUTHOR]

The hair follicle can cycle throughout a lifetime, undergoing periods of growth (anagen), regression (catagen) and relative quiescence (telogen). The time that a hair follicle spends in each of these stages is crucial to determine the length of hair fibre that it produces. Perturbations in this regard can manifest in various hair diseases such as anagen effluvium, or acute and chronic telogen effluvium. The established 'dogma' when considering how many hair follicles there are in each stage has long been that the majority are in anagen (85%–90%), followed by telogen (10%–15%) and catagen (1%–2%). These values are based on various studies using different methodologies such as hair plucking, phototrichograms and histology. However, these methods have flaws when it comes to differentiating between catagen and telogen follicles. We sought to determine the catagen: telogen ratio through the ex vivo stereomicroscopic examination of hundreds of hair follicles removed from the occipital scalp of 14 Caucasian males during routine hair transplantation procedures. Using this methodology, and in agreement with a similar observation by another research group, we found that the percentage of catagen hair follicles was higher (7.5%) than telogen (3.5%) in all patients assessed. Consequently, we believe that the percentage of catagen follicles is clearly underestimated and therefore challenge the current established dogma. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alopecia significantly affects the mental health and social relationship of women since childbearing age, highlighting the need for a safe, effective, and convenient treatment. RESULTS: Comparing the photographs taken before and after the intervention, 67% of patients' hair density increased from 151 6 39.82 hairs/cm² (preintervention) to 170.96 6 37.14 hairs/cm² (at 24-week follow-up), representing an approximate increase of 19 hairs/cm². Meanwhile, hair follicle density increased by approximately 15 follicles/cm² after 24 weeks since the first treatment, rising from 151.04 6 41.99 follicles/cm² to 166.72 6 37.13 follicles/cm². The primary adverse reactions observed were local swelling and pain due to injections. METHODS: The authors have conducted a prospective self-controlled trial involving 15 female patients at childbearing age with alopecia. These patients received a subcutaneous scalp injection of platelet-rich plasma once every 4 weeks for 3 treatments in total. Outcome measurements were included below: changes in hair density (hair/cm²), hair follicle density (hair follicle/cm²), and overall photographic assessment (improved or not) at 4, 12, and 24 weeks right after the first treatment. CONCLUSION: Local injection of nonactivated platelet-rich plasma with low leukocytes concentration could be an effective strategy to alleviate alopecia symptoms in female patients. [ABSTRACT FROM AUTHOR]

Abnormal healing following skin injury, such as slow healing and scar formation, can significantly affect an individual's life. Complex treatment methods and cumbersome instruments have reduced the efficacy of treating such diseases. In this study, a novel biocompatible liquid metal (LM) composite wound dressing (LGPU) is designed by synthesizing polyurea polyurethane (PU) and blending it with LM modified with glutathione (GSH), a bioactive three‐peptide compound. The effects of external electrical stimulation (ES) on wound‐induced hair follicle neogenesis are explored. The dressings exhibited a few important properties, including conductivity, high stretchability, recyclability, and, most importantly, excellent self‐healing capacity, owing to the liquid nature of the LM fillers and the highly dynamic characteristics of hydrogen bonds. Furthermore, the combination therapy with LGPU and ES promoted fibroblast migration and accelerated wound healing. The wounds treated with the combination therapy fully healed in nine days, while the wounds in the blank group are still in a scabbing state. Remarkably, this treatment method can activate the regeneration and healthy growth of hair follicles at the site of injury, which is beneficial for reducing wound scarring. Collectively, this innovative therapy provides a facile strategy to accelerate skin wound healing and achieve scar‐free repair. [ABSTRACT FROM AUTHOR]

The feather growth rate in chickens included early and late feathering. We attempted to characterize the genes and pathways associated with the feather growth rate in chickens that are not in agreement with Mendelian inheritance. Gene expression profiles in the hair follicle tissues of late-feathering cocks (LC), early-feathering cocks (EC), late-feathering hens (LH), and early-feathering hens (EH) were acquired using RNA sequencing (RNA-seq), mass spectrometry (MS), and quantitative reverse transcription PCR (qRT‑PCR). A total of 188 differentially expressed genes (DEGs) were ascertained in EC vs. LC and 538 DEGs were identified in EH vs. LH. We observed that 14 up-regulated genes and 9 down-regulated genes were screened both in EC vs. LC and EH vs. LH. MS revealed that 41 and 138 differentially expressed proteins (DEPs) were screened out in EC vs. LC and EH vs. LH, respectively. Moreover, these DEGs and DEPs were enriched in multiple feather-related pathways, including JAK-STAT, MAPK, WNT, TGF-β, and calcium signaling pathways. qRT-PCR assay showed that the expression of WNT8A was decreased in LC compared with EC, while ALK and GRM4 expression were significantly up-regulated in EH relative to LH. This study helps to elucidate the potential mechanism of the feather growth rate in chickens that do not conform to genetic law. [ABSTRACT FROM AUTHOR]

This article discusses the use of a non-invasive scanning technique called cellular resolution full-field optical coherence tomography (CRFF-OCT) to analyze the features of melasma, a skin condition associated with photoaging. The study found that melasma lesions had significantly higher numbers and activities of activated melanocytes, resulting in spinous hyperpigmentation and increased vascularity compared to nearby perilesions. However, there were no significant differences in basal hyperpigmentation, basement membrane disruption, melanophages, inflammatory cells, or collagen degradation between the two. The findings suggest that photodamage is present in the facial skin of patients with melasma, and treatment should focus on rejuvenating the entire dermis. [Extracted from the article]

Objective: Dandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff‐affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune privilege (HF IP) remain unknown. Here, we characterised the HF immune microenvironment and immune privilege status in dandruff‐affected scalp skin. Methods: We assessed relevant key parameters in healthy versus dandruff‐affected human scalp biopsies using quantitative immunohistomorphometry, laser capture microdissection, and RNA sequencing. Results: The number of epidermal CD4+ and CD8+ T cells was increased in lesional dandruff scalp skin, while the number of MHC class II+/CD1a+ Langerhans cells was decreased in the infundibulum. The number of intrafollicular and perifollicular CD4+ T cells and CD8+ T cells, perifollicular CD68+ macrophages, and tryptase+ mast cells remained unchanged. Interestingly, MHC class Ia and ß2‐microglobulin protein expression were significantly increased specifically in the suprabulbar outer root sheath (ORS) compartment of dandruff‐associated HFs. RNAseq analysis of laser capture micro‐dissected suprabulbar ORS compartment revealed antigen presentation pathway as the top regulated canonical pathway, along with the upregulation of HF‐IP genes such as HLA‐C, HLA‐DP, and TAP1, which are normally down‐regulated in healthy HFs. Intrafollicular protein expression of known HF IP guardians (CD200 and α‐MSH) and 'danger signals' (MICA and CXCL10) remained unaltered at the IP sites of dandruff lesional HFs compared to non‐lesional and healthy HFs. Instead, the expression of macrophage migration inhibiting factor (MIF), another HF IP guardian, was reduced. Conclusion: Together, this work shows that dandruff is associated with epidermal T‐cell infiltration and a weakened HF IP in the suprabulbar ORS of HFs in dandruff lesional scalp. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aldehyde dehydrogenase 2 (ALDH2) levels in human hair follicles (HFs) are significantly increased during the anagen phase. • ALDH2 expression is primarily localized in the outer root sheath of human HFs. • Activation of ALDH2 in HFs leads to anagen induction and subsequent hair shaft elongation. • ALDH2 activation triggers reactive oxygen species scavenging in HFs and upregulates β-catenin signaling. • Modulation of ALDH2 may be a promising therapeutic approach for inducing the anagen phase, providing novel insights into the impact of ALDH2 activation on HFs. Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion. To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion. The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2′,7′- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen. During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs. Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction. [ABSTRACT FROM AUTHOR]

Delayed wound healing induced by bacterial infection and a persistent inflammatory response remains a great clinical challenge. Herein, we reported a paintable, anti-bacterial, and anti-inflammatory Nap-F3K-CA (Nap-Phe-Phe-Phe-Lys-Caffeic Acid) hydrogel for burn wound management based on caffeic acid (CA)-functionalized short peptides (Nap-Phe-Phe-Phe-Lys). Hydrogels are assembled by non-covalent interactions between gelators, and the incorporation of CA promotes the self-assembly of the hydrogel. After being applied to burn wounds, the hydrogel effectively adapted to irregular wound beds and maintained a moist protective environment at the wound. The Nap-F3K-CA hydrogel can scavenge ROS to relieve oxidative damage and downregulate proinflammatory levels. The Nap-F3K-CA hydrogel also displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria, which reduced the incidence of wound infections. Moreover, the hydrogel exhibited good biocompatibility and hemostatic function. In vivo experiments demonstrated that the Nap-F3K-CA hydrogel significantly accelerated the repair of the skin structure including promoting collagen deposition, vascular regeneration, and hair follicle formation. These findings proved the clinical application potential of the Nap-F3K-CA hydrogel as a promising burn wound dressing. [ABSTRACT FROM AUTHOR]

Prostaglandin D2 (PGD2) levels are high in the balding areas of human scalps, and PGD2 has been found to inhibit hair growth. It is known that the inhibition of the PGD2 receptor can promote hair growth by preventing hair follicles from entering the catagen phase. Thus, we identified an antagonist of DP2, the receptor for PGD2, as a potential treatment for hair loss using an AI-based DeepZema® drug development program. In this study, we identified that the DP2 antagonist (DP2A) could ameliorate alopecia in human follicle dermal papilla cells (HFDPCs) that were stimulated by dihydrotestosterone (DHT), a known molecule related to hair loss. We observed that the DP2A promoted wound healing efficiency and increased alkaline phosphatase levels in the HFDPCs that were damaged with DHT. In addition, we found that the DP2A diminished the reactive oxygen species (ROS) levels generated in the DHT-damaged HFDPCs. We confirmed that the DP2A effectively recovered the membrane potential of mitochondria in these cells. We also demonstrated that the DP2A enhanced the phosphorylation levels of both Akt and ERK in the HFDPCs that were damaged with DHT. Notably, we revealed that the DP2A slightly enlarged the three-dimensional spheroid size in these cells and confirmed that the DP2A improved hair growth in the organ culture of human hair follicles. Taken together, we suggest that DP2A has therapeutic effects on HFDPCs that are damaged by DHT and holds promise as a potential treatment for treating hair loss. [ABSTRACT FROM AUTHOR]

Permanent makeup (PMU) is a popular form of tattooing applied to the eyebrows, eyelids, and lips for corrective and aesthetic purposes. It also has medical applications, such as reconstructing the breast areola, mimicking hair follicles on the head, and covering scars and vitiligo. Unlike body tattoos, PMU often requires reapplication to maintain color density and shape, as the pigments fade over time. This fading is likely due to the characteristics of PMU colorants rather than the application methods or apparatuses. The aim of our study was to assess the application depth of PMU colorants and tattoo ink after procedures. PMU colorants typically contain larger pigment particles in their composition compared to the nanoparticles found in traditional tattoo inks. We applied both tattoo ink and PMU colorants on SKH-1 mice using a PMU apparatus and a tattoo apparatus. To clarify the semi-permanent nature of PMU compared to the more permanent body tattoos, skin biopsies were performed at various intervals throughout this study. The results showed that PMU and tattoo ink were placed at approximately the same depth but exhibited key differences in behavior. PMU with larger inorganic pigments fades over time, while tattoos with smaller, stable organic pigments ensure permanence. [ABSTRACT FROM AUTHOR]

Simple Summary: The dermal papilla (DP) is a specialized mesenchymal compartment that forms at the base of the hair follicle. It acts as a signaling center that regulates hair growth, shape, size, and color. Dermal papilla cells (DPCs) exhibit stem cell properties and show significant potential for use in cell therapy. They can be induced into other functional cells, regenerate skin tissues and new hair follicles when combined with epithelial stem cells, and promote hair growth and wound healing when administered on the skin. This review summarizes the functions of DPs in the hair follicle, shows how DPCs could be used in cell therapy, and discusses the challenges and recent advances in the field, from basic research to translational applications. As an appendage of the skin, hair protects against ultraviolet radiation and mechanical damage and regulates body temperature. It also reflects an individual's health status and serves as an important method of expressing personality. Hair loss and graying are significant psychosocial burdens for many people. Hair is produced from hair follicles, which are exclusively controlled by the dermal papilla (DP) at their base. The dermal papilla cells (DPCs) comprise a cluster of specialized mesenchymal cells that induce the formation of hair follicles during early embryonic development through interaction with epithelial precursor cells. They continue to regulate the growth cycle, color, size, and type of hair after the hair follicle matures by secreting various factors. DPCs possess stem cell characteristics and can be cultured and expanded in vitro. DPCs express numerous stemness-related factors, enabling them to be reprogrammed into induced pluripotent stem cells (iPSCs) using only two, or even one, Yamanaka factor. DPCs are an important source of skin-derived precursors (SKPs). When combined with epithelial stem cells, they can reconstitute skin and hair follicles, participating in the regeneration of the dermis, including the DP and dermal sheath. When implanted between the epidermis and dermis, DPCs can induce the formation of new hair follicles on hairless skin. Subcutaneous injection of DPCs and their exosomes can promote hair growth. This review summarizes the in vivo functions of the DP; highlights the potential of DPCs in cell therapy, particularly for the treatment of hair loss; and discusses the challenges and recent advances in the field, from basic research to translational applications. [ABSTRACT FROM AUTHOR]

Background and Objectives: Alopecia areata (AA) is a tissue-specific immune-mediated disorder that affects hair follicles and the nail apparatus. Due to the collapse of hair follicle immune privilege in AA, hair loss ranges in severity from small, localized patches on the scalp to the loss of entire body hair. Although AA is of uncertain etiology, the disease has a common genetic basis with a number of other autoimmune diseases. Materials and Methods: To identify candidate genes that confer susceptibility to AA in the Jordanian population and further understand the disease background, we performed DNA genotyping using case–control samples of 152 patients and 150 healthy subjects. Results: While no significant result was observed in the ten single-nucleotide polymorphisms (SNPs), CLEC4D rs4304840 variants showed significant associations with AA development within our cohort (p = 0.02). The strongest associations were for the codominant and recessive forms of rs4304840 (p = 0.023 and p = 0.0061, respectively). Conclusions: These findings suggest that CLEC4D gene variants may contribute to AA pathogenesis among Jordanians. Further advanced genetic analysis and functional investigations are required to elucidate the genetic basis of the disease. [ABSTRACT FROM AUTHOR]

Background: Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis. Results: We report generation of Alx4f/f conditional mice and show that tissue‐specific Cre‐mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4‐null mice but without affecting postnatal survival. While Alx4‐null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development. Conclusion: The Alx4f/f mice provide a valuable resource for systematic investigation of cell type‐ and stage‐specific function of ALX family transcription factors in development and disease. Key Findings: We report successful generation and analysis of Alx4 conditional mice.We demonstrate lineage‐specific requirements of Alx4 in craniofacial, limb, and hair development.Our results demonstrate that Alx4 functions in multiple lineages to control hair follicle development.The Alx4 conditional mice provide a valuable and unique resource for systematic characterization of the cellular and molecular mechanisms involving the ALX family transcription factors in development and disease. [ABSTRACT FROM AUTHOR]

Mice hair follicles (HFs) are a valuable model for studying various aspects of hair biology, including morphogenesis, development, and regeneration due to their easily observable phenotype and genetic manipulability. The initiation and progression of hair follicle morphogenesis, as well as the hair follicle cycle, are regulated by various signaling pathways, of which the main role is played by the Wingless-type MMTV integration site family (Wnt) and the Bone Morphogenic Protein (BMP). During the hair follicle cycle, the BMP pathway maintains hair follicle stem cells (HFSCs) in a dormant state while the Wnt pathway activates them for hair growth. Given the pivotal role of the Wnt pathway in hair biology and HFSCs regulation, we investigated the influence of the Wnt modulator - R-spondin 3 (Rspo3), in these processes. For this purpose, we developed a transgenic mice model with the overexpression of Rspo3 (Rspo3GOF) in the whole ectoderm and its derivatives, starting from early morphogenesis. Rspo3GOF mice exhibited a distinct phenotype with sparse hair and visible bald areas, caused by reduced proliferation and increased apoptosis of hair matrix progenitor cells, which resulted in a premature anagen-to-catagen transition with a shortened growth phase and decreased overall length of all hair types. In addition, Rspo3GOF promoted induction of auchene and awl, canonical Wnt-dependent hair type during morphogenesis, but the overall hair amount remained reduced. We also discovered a delay in the prebulge formation during morphogenesis and prolonged immaturity of the HFSC population in the bulge region postnatally, which further impaired proper hair regeneration throughout the mice's lifespan. Our data supported that Rspo3 function observed in our model works in HFSCs' formation of pre-bulge during morphogenesis via enhancing activation of the canonical Wnt pathway, whereas in contrast, in the postnatal immature bulge, activation of canonical Wnt signaling was attenuated. In vitro studies on keratinocytes revealed changes in proliferation, migration, and colony formation, highlighting the inhibitory effect of constitutive overexpression of Rspo3 on these cellular processes. Our research provides novel insights into the role of Rspo3 in the regulation of hair morphogenesis and development, along with the formation and maturation of the HFSCs, which affect hair regeneration. [ABSTRACT FROM AUTHOR]

Obesity is a complex multifactorial disease in which excess body fat triggers negative health effects. Systemically, obesity causes several changes, such as inflammation, oxidative stress, mitochondrial dysfunction and apoptosis; factors linked to the slow and incomplete epithelial regenerative process. Specifically, in the integumentary system, obesity causes an expansion of the skin's surface area and changes in collagen deposition. Molecular underpinnings of why obesity delays wound healing are still poorly understood. In addition to the primary role of dermal adipocytes in lipid storage and heat insulation, they also promote skin immunity, wound healing and hair follicle cycling. As a consequence of the cellular and dysfunctional adaptations of adipocytes, inflammatory immune alterations, alteration in the expression of proteins genes associated with the blood supply, altered collagen formation through fibroblast senescence and excessive degradation of extracellular matrix proteins are metabolic characteristics of the system in obesity that contribute to sustained inflammation and decreased mechanical resistance of the skin. [ABSTRACT FROM AUTHOR]

We previously showed that inhibition of glycolysis in cutaneous squamous cell carcinoma (SCC)-initiating cells had no effect on tumorigenesis, despite the perceived requirement of the Warburg effect, which was thought to drive carcinogenesis. Instead, these SCCs were metabolically flexible and sustained growth through glutaminolysis, another metabolic process frequently implicated to fuel tumorigenesis in various cancers. Here, we focused on glutaminolysis and genetically blocked this process through glutaminase (GLS) deletion in SCC cells of origin. Genetic deletion of GLS had little effect on tumorigenesis due to the up-regulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We went on to show that posttranscriptional regulation of nutrient transporters appears to mediate metabolic flexibility in this SCC model. To define the limits of this flexibility, we genetically blocked both glycolysis and glutaminolysis simultaneously and found the abrogation of both of these carbon utilization pathways was enough to prevent both papilloma and frank carcinoma. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusion The robotic hair transplant technology, ARTAS, has a series of fine mechanical structure and an intelligent recognition system that allows it to independently select hair follicular units (FUs) and effectively harvest hair. After entering China in 2016, ARTAS has attracted the attention of hair transplant surgeons and hair loss patients given its advantages in a short learning curve and simple operation.To compare the efficacy and safety between the ARTAS system and follicular unit excision (FUE) in the treatment of male androgenetic alopecia (AGA) and to further promote the improvement and upgrading of ARTAS technology concerning hair transplantation.Thirteen Chinese male patients with Norwood–Hamilton II–IV AGA aged 25–35 years were enrolled in this study. The donor site of each patient was randomly divided into left and right regions, receiving ARTAS on one side and FUE on the other. Yield, transection, and discard rates of hair FUs from both sides were compared. Safety of the procedures in whole, as well as follow‐up results were investigated and evaluated.The total yield rate on the ARTAS side was lower than on the FUE side (82.05% vs. 90.03%, p > 0.05); the total discard rate on the ARTAS side was higher than on the FUE side (10.71% vs. 5.46%, p < 0.05); the total transection rate on the ARTAS side was lower than on the FUE side (13.17% vs. 13.96%, p > 0.05). No significant difference was found in patient satisfaction (efficacy), and no side effects or complications were detected during or after all surgeries.The current iteration of Robotic hair transplant technology is effective and safe, and can be recommended for AGA hair transplantation surgery. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a pervasive skin disease characterized by inflammation of sebaceous units surrounding hair follicles. It results from the complex interplay between skin physiology and the intricate cutaneous microbiome. Current acne treatments, while effective, have major limitations, prompting a shift towards microbiome‐based therapeutic approaches. This study aims to determine the relationship between acne and the cutaneous microbiome, assess the effects of current treatments on the cutaneous microbiome and explore the implications for developing new therapies. A systematic review was performed using PubMed and SCOPUS databases within the last 10 years. Methodological quality was assessed independently by two authors. The search retrieved 1830 records, of which 26 articles met the inclusion criteria. Meta‐analysis of alpha diversity change was assessed using fixed and randomized effect models per therapeutic group. Eight studies pertain to the role of the cutaneous microbiome in acne, identifying C. acnes, S. aureus and S. epidermidis as key contributors through overproliferation, commensalism or dysbiosis. Eleven studies discuss current acne treatments, including doxycycline (1), topical benzoyl peroxide (BPO) (4), isotretinoin (2), sulfacetamide‐sulfur (SSA) (2) and aminolevulinic acid‐photodynamic therapy (ALA‐PDT) (2), identified as modulating the cutaneous microbiome as a mechanism of efficacy in acne treatment. Seven studies discuss new treatments with topical probiotics, plant derivatives and protein derivatives, which contribute to acne clearance via modulation of dysbiosis, inflammatory markers and diversity indexes. A meta‐analysis of the effects of existing therapeutics on the cutaneous microbiome identified benzoyl peroxide as the only treatment to facilitate significant change in diversity. Despite the heterogeneity of study types and microbiome classifications limiting the analysis, this review underscores the complexity of microbial involvement in acne pathogenesis. It delineates the effects of acne therapeutics on microbial diversity, abundance and composition, emphasizing the necessity for personalized approaches in acne management based on microbiome modulation. [ABSTRACT FROM AUTHOR]

Both alopecia areata (AA) and vitiligo share common pathogenesis involving, interferon‐γ (IFN‐γ) and interleukin‐15 (IL‐15) signalling pathways that activate cytotoxic CD8+ T lymphocytes. These shared mechanisms may explain why both diseases respond to currently available treatments (e.g. topical/systemic corticosteroid) and emerging treatment modalities. As compared with the speed of re‐pigmentation in vitiligo lesions, the regeneration of pigmented terminal hair follicles in AA lesions appears fast in response to treatments targeting the inhibition of the Janus kinases (JAKs) and other kinases. We summarize the commonalities and differences between AA and vitiligo focusing on the treatment modalities, followed by recent findings associated with hair follicle stem cells (HFSC) in hair bulge (HBg) and melanocyte stem cells (McSC) in HBg and hair germ (HGm). We then discuss how HFSC and HGm‐McSC are involved in the initiation of anagen phase, followed by pigmented terminal hair regrowth in the recovering AA lesions in association with immunology. We also discuss how HBg‐McSC contribute to the migration of fully dendritic mature melanocytes into interfollicular epidermis and the equal distribution of melanin in recovering vitiligo lesions. Finally, we present four hypotheses to elucidate the delayed distribution of melanin by mature melanocytes in depigmented vitiligo lesions from the aspects of stem cell biology, as compared with quick hair recovery in AA: (1) McSC are less abundant than HFSC. (2) McSC require a long travel, whereas HFSC reside close to hair regeneration trigger point. (3) Keratinocyte scaffold to accept melanin is not well preserved, whereas scaffold for hair regrowth is well preserved. (4) Inhibitors targeting JAKs and other kinases have less direct effects on melanocyte proliferation and differentiation in vitiligo than hair regrowth in AA. Our review provides an overview of treatment modalities and bridges the gap between scientific advancement and clinical practice in AA and vitiligo management. [ABSTRACT FROM AUTHOR]

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole‐treated groups, we revealed that MLT supplementation significantly up‐regulated Wnt/β‐catenin signalling pathway‐related genes. In‐depth analysis of the expression of key molecules in the Wnt/β‐catenin signalling pathway revealed that MLT up‐regulated the Wnt/β‐catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP‐HFSCs co‐culture system, we verified that MLT activated Wnt/β‐catenin signalling in DPs when co‐cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/β‐catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans. [ABSTRACT FROM AUTHOR]

Chronic skin wounds are estimated to affect 6.5 million patients in the US, at a cost of over USD 25 billion. Efforts to prevent and/or treat such wounds will result in reduced morbidity and economic losses. This project is focused on the role of vitamin D signaling in the epidermis in the control of stem cell (SC) activation and function during the initial response to the wounding of the skin, a response that, if defective, contributes to poor wound healing or cancer. In this review, I first describe the anatomy of the skin, focusing first on the epidermis, describing the different cell layers which in a spatial way also represent the differentiation process of the interfollicular epidermis (IFE) as it undergoes continuous regeneration. I then describe the other components of the skin, particularly the hair follicle (HF), which undergoes a cyclic pattern of regeneration. Adult SCs residing in these regenerative tissues play essential roles in the maintenance of these tissues. However, when the skin is wounded, the progeny of SCs from all regions of the HF and IFE contribute to the healing process by changing their initial cell fate to take on an epithelial genotype/phenotype to heal the wound. Although earlier lineage tracing studies helped to define the contributions SCs from the different niches made to wound healing, scRNAseq studies have demonstrated a considerably more nuanced picture. The role of vitamin D signaling will be introduced by reviewing the unique role played by the epidermal keratinocyte first in producing vitamin D and then in metabolizing it into its active form 1,25(OH)2D. 1,25(OH)2D is the principal ligand for the vitamin D receptor (VDR), a transcription factor that helps to mediate the genomic changes in the stem cells in their response to wounding. In these actions, the VDR is regulated by coregulators, of which the steroid receptor coactivator complexes SRC 2 and 3 and the mediator complex (MED) play essential roles. The VDR generally acts in association with other transcription factors such as p63 and β-catenin that can colocalize with the VDR in the genes it regulates. Although much remains to be understood, the role of the VDR in the stem cell response to wounding is clearly essential and quite different from its classic roles in regulating calcium metabolism, although calcium is essential for the actions of vitamin D signaling in the skin. [ABSTRACT FROM AUTHOR]

Background: Bilateral cleft lip palate is a severe congenital birth defect of the mouth and face. Immunity factors modulate immune response, inflammation, and healing; therefore, they are vital in the assessment of the immunological status of the patient. The aim of this study is to assess the distribution of Gal-10, CD-163, IL-4, IL-6, IL-10, HBD-2, HBD-3, and HBD-4 in tissue of the bilateral cleft lip palate in primary dentition children. Methods: Five patients underwent cheiloplasty surgery, where five tissue samples of lip were obtained. Immunohistochemical staining, semi-quantitative evaluation, and non-parametric statistical analysis were used. Results: A statistically significant increase in HBD-2, HBD-3, and HBD-4 was found in skin and mucosal epithelium, hair follicles, and blood vessels. A notable increase was also noted in IL-4, IL-6, and IL-10 in the mucosal epithelium and CD163 in blood vessels. The connective tissue of patients presented with a statistically significant decrease in Gal-10, IL-10, and HBD-3. Spearman's rank correlation revealed multiple significant positive and negative correlations between the factors. Conclusions: Upregulation of CD163 points to increased angiogenesis but the increase in IL-4 and IL-10 as well as the decrease in Gal-10 points to suppression of excessive inflammatory damage. Decreased connective tissue healing and excessive scarring are suggested by the decrease in HBD-3 and IL-10 and the increase in IL-6. [ABSTRACT FROM AUTHOR]

Docetaxel is a commonly used taxane chemotherapeutic agent in the treatment of a variety of cancers, including breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, gastric cancer, and head and neck cancer. Docetaxel exerts its anti-cancer effects through inhibition of the cell cycle and induction of proapoptotic activity. However, docetaxel also impacts rapidly proliferating normal cells in the scalp hair follicles (HFs), rendering the HFs vulnerable to docetaxel-induced cell death and leading to chemotherapy-induced alopecia (CIA). In severe cases, docetaxel causes persistent or permanent CIA (pCIA) when hair does not grow back completely six months after chemotherapy cessation. Hair loss has severe negative impacts on patients' quality of life and may even compromise their compliance with treatment. This review discusses the notable prevalence of docetaxel-induced CIA and pCIA, as well as their prevention and management. At this moment, scalp cooling is the standard of care to prevent CIA. Treatment options to promote hair regrowth include but are not limited to minoxidil, photobiomodulation (PBMT), and platelet-rich plasma (PRP). In addition, a handful of current clinical trials are exploring additional agents to treat or prevent CIA. Research models of CIA, particularly ex vivo human scalp HF organ culture and in vivo mouse models with human scalp xenografts, will help expedite the translation of bench findings of CIA prevention and/or amelioration to the clinic. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic skin disease, characterized by clinical inflammation of the hair follicle with the recurrence of abscesses, nodules, and tunnels. Recently, several studies suggested a role of IL‐1 family (IL‐1F) cytokines in eliciting and sustaining the disease. The aim of this work is to perform a comprehensive analysis of IL‐1F cytokines, soluble inhibitors and receptors in a cohort of HS patients not treated with biological agents. Sixteen patients affected by HS and 16 healthy controls were recruited; clinical data were collected and disease severity evaluated by means of the International HS Severity Score System (IHS4). Serum levels of IL‐1F cytokines, inhibitors and receptors were measured using a Multiplex Assays. IL‐18 and free IL‐18 levels were significantly higher in patients vs controls. Among soluble inhibitors, IL‐1Ra, IL‐1R2 and ST2/IL‐1R4 were significantly increased. IL‐18, free IL‐18 and IL‐33 levels are strongly correlated with IHS4. Also the inhibitors IL‐1Ra and IL‐18BP show a correlation with IHS4. The data obtained in this study confirm the involvement of IL‐1F cytokines in mediating the disease and determining its severity and suggest a possible role for IL‐18 as novel serum biomarker of active disease. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) innovative preservative on hair follicle activity of rat vibrissae under low temperature conditions. Methods From January 2021 to December 2023, the upper of hair follicle (UHF) from male SD rat vibrissae was used in the experiment. These UHF were equally divided into NS, IGF-1, EGF, and IGF-1+EGF preservation solutions groups. At 3, 6 and 12 hours, the cultured UHF were analyzed by hematoxylin and eosin (HE) staining and alkaline phosphatase (ALP) activity. The UHF co-cultured with NS and IGF-1+EGF for 3 hours were further transplanted into the dorsum of nude mice. After 24 hours, the transplanted UHF was taken to observe by HE staining and ALP activity. Results In vitro preservation, HE staining results indicated that the cultured UHF at 3 hours, the follicle structure and cell arrangement were normal without obvious changes. At 12 hours, only the IGF-1+EGF group had intact follicle structure and clear organization. Moreover, ALP values showed that the IGF-1+EGF group at 3, 6 and 12 hours were significantly higher than the NS group (P＜0.001). Overall, ALP activity gradually decreased over time. In vivo transplantation, HE staining results showed that the IGF-1+EGF group were structurally distinct with orderly cell arrangements, compared to the NS group. ALP values were significantly higher than NS group (P＜0.05). Conclusion The innovative preservation solutions containing IGF-1 and EGF under low temperatures, can effectively enhance the activity of UHF, and promote the success of hair follicle transplantation. [ABSTRACT FROM AUTHOR]

Background: Alopecia Areata (AA) is an autoimmune disease that targets hair follicles and is driven by T cells specific to that organ. As it was found that the lack of expression of VDRs is associated with reduced hair follicle growth and epidermal differentiation. The aim of this study was to evaluate the efficacy and safety of intralesional vitamin D and to assess it by the dermoscope. Methods: This study is A clinical trial study that included 20 patients with alopecia areata, who received intralesional injection of vitamin D (an aqueous preparation of cholecalciferol (Devarol ampule 200000iu/2ml, Memphis, Egypt) (2.5mg/ml) the maximum total amount of Vitamin D3 injected in every session was 1.25mg (0.5ml).Treatment of alopecia areata was done according to the study protocol and the patients were evaluated at initial Visit, every 2 weeks during treatment sessions and 3 months after completion of therapy. Results: There was no statistical significance change in SALT score among our group patients post treatment compared to pretreatment, regarding clinical response there was 10% of cases (2 patients) shows hair regrowth by >25% (A2) and majority of patients 75% (15 patients) shows minimal hair regrowth by < 25% (A1), 15% of cases (3 patients) showed no improvement at all, there was erythema, itching and pain assessed among study cases (20%, 15% and 15% respectively). Atrophy and telangiectasia were found among 5% in cases. Conclusions: Intralesional Vitamin D (cholecalciferol) is a mild effective treatment of Alopecia Areata. [ABSTRACT FROM AUTHOR]

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]

Background: Diabetes mellitus (DM) is known to inhibit skin self-renewal and hair follicle stem cell (HFSC) activation, which may be key in the formation of chronic diabetic wounds. This study aimed to investigate the reasons behind the suppression of HFSC activation in DM mice. Methods: Type 1 DM (T1DM) was induced in 6-week-old mice via streptozotocin, and hair follicle growth was subsequently monitored. RNA sequencing, bioinformatics analyses, qRT‒PCR, immunostaining, and cellular experiments were carried out to investigate the underlying mechanisms involved. Results: T1DM inhibited HFSC activation, which correlated with an increase in caspase-dependent programmed cell death. Additionally, T1DM triggered apoptosis and pyroptosis, predominantly in HFSCs and epidermal regions, with pyroptosis being more pronounced in the inner root sheath of hair follicles. Notably, significant cutaneous immune imbalances were observed, particularly in macrophages. Cellular experiments demonstrated that M1 macrophages inhibited HaCaT cell proliferation and induced cell death, whereas high-glucose environments alone did not have the same effect. Conclusion: T1DM inhibits HFSC activation via macrophage reprogramming-mediated caspase-dependent pyroptosis, and there is a significant regional characterization of cell death. Moreover, T1DM-induced programmed cell death in the skin may be more closely related to immune homeostasis imbalance than to hyperglycemia itself. These findings shed light on the pathogenesis of diabetic ulcers and provide a theoretical basis for the use of hair follicle grafts in wound repair. [ABSTRACT FROM AUTHOR]

Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network. Editor's summary: Langerhans cells (LCs) are specialized skin-resident antigen-presenting cells that not only share developmental origins with tissue-resident macrophages but also acquire the dendritic cell–like ability to migrate to draining lymph nodes. How this dual LC identity is imprinted and maintained is not completely understood. Using a mouse model of adult LC repopulation, Appios et al. found that both the developmental origin of repopulating monocytes and epidermal niche signaling imprint LC identity. A subset of infiltrating monocytes underwent stepwise differentiation involving loss of Zeb2-regulated macrophage identity, Jagged/Notch-dependent imprinting of LC fate, and survival signals in the epidermis. Similar developmental programs were detected among human embryo–derived LCs in postnatal skin. Together, these findings identify intrinsic and extrinsic factors guiding LC specification in the skin. —Claire Olingy [ABSTRACT FROM AUTHOR]