Search Results (280)

Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during anagen and is markedly enriched in secondary HFSCs relative to hair matrix cells (HMCs), suggesting a role in initiating follicle regeneration. Functional assays show that S100a4 promotes HFSCs into a dynamically regulated state that activates stem cell competence while facilitating differentiation, with overexpression upregulating epidermal and follicular differentiation markers (Ivl, Cux1, K14, Klk5), as well as pluripotency genes (Itga6, Krt15), while knockdown suppresses these programs. Proteomic analysis further reveals direct interactions between S100A4 and keratins critical for hair follicle and epidermal development (KRT5, KRT14, KRT8, KRT18), suggesting a structural and regulatory interface through which S100A4 modulates HFSC fate. Collectively, these results establish S100a4 as a central modulator of secondary HFSC function and provide mechanistic insight into the molecular control of hair follicle regeneration, with potential implications for improving cashmere fiber production. Full article

Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article

Opophytum forskahlii has a well-established ethnopharmacological significance. This study aimed to assess the skin anti-aging and hair growth-promoting activities of O. forskahlii seed oil (OFSO) and the underlying mechanism. GC-MS profiling revealed high levels of unsaturated fatty acids, linoleic acid (55.46%), and oleic acid (38.54%). The skin anti-aging activity of OFSO (3.125–100 µg/mL) was evaluated in normal human dermal fibroblasts (NHDFs) using MTT and enzyme inhibition assays. OFSO was non-cytotoxic and enhanced fibroblast proliferation in a dose-dependent manner, reaching 145.5% of control at 100 µg/mL (p < 0.05). OFSO significantly (p < 0.05) inhibited collagenase (48%), hyaluronidase (53%), elastase (57%), and tyrosinase (55%). The oil showed anti-inflammatory activity by inhibiting COX-1 and COX-2 (0.01–100 µg/mL) with IC₅₀ = 0.125 and 0.014 µg/mL, respectively. The hair growth promoting efficacy was assessed using adult male Wistar rats, randomly divided into control, OFSO-treated, and 2% minoxidil-treated groups (5 rats/group). Hair growth was assessed through visual scoring over 14 days of topical application and confirmed by histological examination and hair follicle counting. On day 14, the OFSO-treated group displayed almost complete hair coverage (score about 5.0), exceeding minoxidil (about 4.0), and significantly increased hair follicle number (14.0 ± 1 vs. 9.2 ± 0.8, p < 0.05). Histology confirmed that OFSO promoted hair follicle growth, differentiation, and transition from the telogen to the anagen phase. Network pharmacology analysis, integrating targets predicted via SwissTargetPrediction and disease-associated genes from GeneCards, identified PPARG, ESR1, and IL6 as key hub genes underlying OFSO’s effects. PPARG enhances antioxidant defenses, anti-inflammatory responses, and sebaceous gland function; ESR1 supports collagen production, skin elasticity, and follicle vascularization; and IL6 modulates inflammation and triggers the anagen phase of hair growth. Functional enrichment revealed modulation of PPAR, estrogen, prolactin, and arachidonic acid metabolism pathways, suggesting that OFSO may regulate lipid metabolism, inflammation, hormonal signaling, and tissue regeneration. OFSO demonstrated promising anti-aging and hair growth activities, supporting further development and testing of cosmetic formulations. Full article

Dermal papilla cells (DPCs) serve as the signaling hub regulating hair follicle (HF) development and cyclical growth. This study aims to investigate the biological function and molecular mechanisms of TGFBR1 (transforming growth factor β receptor 1), a differentially expressed gene identified through single-cell transcriptomic sequencing (scRNA-seq) in the DPCs from fine-wool sheep. Primary DPCs were isolated and purified using a combination of enzymatic digestion and mechanical dissociation, followed by immunofluorescence identification (α-SMA and SOX2-positive). Following successful transfection with constructed TGFBR1 overexpression plasmids and siRNA interference vectors, cell proliferation was assessed via EDU staining and CCK-8 assays. mRNA expression of key genes in Wnt/β-catenin, BMP, and Notch signaling pathways (PCNA, CCND1, CTNNB1, SFRP2, BMP2, NOTCH3, SMAD4, etc.) was validated by RT-qPCR. Single-cell transcriptomics revealed significant downregulation of TGFBR1 in DPCs from fine-wool sheep. Functional validation demonstrated that TGFBR1 overexpression markedly suppressed DPC proliferation, whereas knockdown of TGFBR1 expression promoted DPC proliferation. Molecular mechanism studies showed that TGFBR1 overexpression significantly downregulated PCNA, CCND1, CTNNB1, NOTCH3, and SMAD4 while upregulating SFRP2, BMP2, and TGFB1 expression. These findings demonstrate that TGFBR1 acts as a negative regulator of DPCs proliferation by modulating the activity of multiple signaling pathways, including Wnt/β-catenin, BMP, and Notch, thereby suppressing the proliferative capacity of DPCs. This study not only provides new theoretical support for elucidating the role of the TGF-β signaling pathway in H development but also offers theoretical reference for in-depth research on molecular breeding in ultra -fine-wool sheep and the molecular mechanisms underlying HF development. Full article

Alopecia areata (AA) is a chronic autoimmune disease characterized by non-scarring hair loss, where pathogenesis is closely linked to the collapse of hair follicle immune privilege and dysregulated T-cell responses. Increasing evidence suggests that gut dysbiosis may contribute to systemic immune alterations relevant to autoimmune disorders, yet its role in AA remains largely unexplored. In this study, we aimed to characterize the gut microbiota composition of AA patients and evaluate its potential as a biomarker for disease discrimination. Fecal samples from patients with AA and healthy controls were analyzed by 16S rRNA sequencing and processed through QIIME2 and MicrobiomeAnalyst platforms. Diversity metrics, differential abundance, and microbial network correlations were assessed, and supervised machine learning models were developed to classify AA versus control profiles. Our results revealed distinct microbial signatures in AA, with enrichment of pro-inflammatory genera such as Methanobrevibacter, Collinsella, and Ruminococcus gnavus, and depletion of immunoregulatory commensals, including Faecalibacterium and Eubacterium eligens group. Network analyses showed more complex microbial interactions in AA, and Random Forest models achieved 92% accuracy in discriminating AA from controls. These findings indicate that gut dysbiosis may play a role in AA pathogenesis, providing potential diagnostic biomarkers and supporting microbiota-targeted interventions as future therapeutic strategies. Full article

Background/Objectives: Transdermal formulations are widely utilized in the pharmaceutical and cosmetic fields because they enable non-invasive administration and sustained local drug delivery. Conventional ex vivo skin permeation experiments using Franz diffusion cells have limitations in capturing the spatial and temporal dynamics of skin penetration. This study aimed to develop a confocal laser scanning microscopy (CLSM)-based approach to visualize and semi-quantitatively assess the penetration behavior of fluorescent dyes with differing lipophilicities. Methods: Four fluorescent dyes with different Log P values—Rhodamine B (Rho-B), Rhodamine 123 (Rho-123), Fluorescein Sodium (Flu-Na), and Nile Red (NR)—were formulated into lotion-based vehicles and applied to excised human abdominal skin. CLSM imaging was performed from 10 min to 240 min post-application. Fluorescence intensities were extracted from depth-resolved regions (R1–R4, 30-μm intervals) to examine penetration kinetics and distribution. Results: CLSM imaging demonstrated that Rho-B penetrated through stratum corneum and entered deep into the skin via the hair follicles. Rho-123 and Flu-Na exhibited intercellular and follicular penetration; however, Flu-Na showed only a slight increase in intensity over time; NR showed negligible penetration into the deeper layers. The results of our analysis indicated that moderately lipophilic substances such as Rho-B and Rho-123 diffused deeply into the skin via both transdermal and follicular routes, whereas highly hydrophobic or lipophilic substances remained in the superficial layers. Conclusions: The CLSM-based approach enabled spatially and temporally resolved, semi-quantitative evaluation of transdermal penetration in a single, non-destructive experiment. Although restricted to fluorescent probes, this approach provides a practical early-stage screening tool for comparing route-specific and time-dependent penetration behaviors of compounds with different lipophilicities. Full article

Hair follicle stem cells (HFSCs) are resident stem cells within hair follicles (HFs) that possess self-renewal and differentiation capacities, serving as a critical model for regenerative medicine research. Their dynamic interaction with dermal papilla cells (DPCs) plays a decisive role in HF development and cycling. FGF22 is a paracrine fibroblast growth factor that can regulate the proliferation, differentiation and migration of epithelial cells. This study established a DPC-HFSC co-culture system, revealing that FGF22 overexpression in DPCs significantly upregulated FGFR1/FGFR2 mRNA expression levels in HFSCs (p < 0.05), with a 1.67-fold increase in EdU-positive cell proportion (p < 0.01). CCK-8 assays demonstrated markedly enhanced HFSC viability (p < 0.01), with a 17% reduction in HFSC apoptosis (p < 0.05). Conversely, FGF22 knockout downregulated FGFR1/FGFR2 expression (p < 0.05), reduced HFSC proliferation capacity by 25% (p < 0.01), and increased HFSC apoptosis levels by 1.81-fold (p < 0.05). In addition, FGF22 overexpression promotes the proliferation and differentiation of HFSCs by activating Wnt/β-Catenin, Sonic Hedgehog (Shh) and Notch signaling pathways, or inhibiting BMP signaling pathways. Knockout of FGF22 weakens these processes and inhibits the activation and differentiation of HFSCs. This study, through the DPCs-HFSCs co-culture system, revealed the regulatory mechanism of FGF22 secreted by DPCs on the proliferation and differentiation of HFSCs, thereby providing theoretical references for fields such as fine-wool sheep breeding, human regenerative medicine, and hair loss treatment. Full article

Androgenetic alopecia (AGA) is the most common type of baldness, characterized by progressive miniaturization of the hair follicle and eventually atrophy. Both genetic and androgenic factors play definite roles in the pathophysiology of the disease, including androgens and growth factors, which induce a crosstalk between the dermal papilla and the hair follicle cells. The goal of AGA treatments is to prevent the hair miniaturization process; however, currently there are only two FDA-approved medications to treat AGA: topical Minoxidil (5% and 2%) for men and women, and oral Finasteride (1 mg tablets—Proscar and Propecia) for men. Nevertheless, these are costly, require lifelong treatment, and may have side effects. Thus, there have been many attempts to develop drugs that can harness the mechanisms controlling the pathogenesis of AGA. These pharmacological therapies might achieve more targeted and effective treatment for the disease. In this review, we present various treatments that have demonstrated their ability to induce hair growth by controlling the pathophysiological mechanisms involved in the development of AGA. Interestingly, treatment by a combination of some drugs has resulted in better outcomes than each of the drugs alone, hence demonstrating the advantage of activating different molecular mechanisms simultaneously. Full article

As essential skin appendages, hair follicles exhibit complex developmental and regenerative processes shaped by the skin microenvironment. Imbalances in skin microenvironmental homeostasis are often accompanied by follicle miniaturization and even hair loss. In studying the mechanisms of hair follicle development, in addition to focusing on the self-regulation of intrinsic signaling within the follicle, it is also crucial to examine the remodeling of the follicular microenvironment triggered by dynamic changes in the skin microenvironment. Herein, we review the individual and combined roles of various cells, tissues, signaling molecules, and metabolic alterations within the skin microenvironment in hair follicle development. Moreover, we summarize the potential applications of the skin microenvironment in treating hair-related diseases, highlight the existing challenges and limitations in the research field, and provide perspectives on future research directions, aiming to elucidate the critical role of the skin microenvironment in regulating hair follicle development. Full article

Purpose: Androgenetic alopecia (AGA) is a common, chronic, non-cicatricial dermatological condition characterized by progressive miniaturization of hair follicles. Although AGA is a benign disorder, it has a considerable impact on patients’ quality of life and psychological health. The current treatment options often demonstrate limited efficacy and are frequently associated with undesirable side effects. This study aimed to co-mill two natural compounds, quercetin (QT) and glycyrrhizic acid (GL), to develop follicle-targeted nanocrystals (NCs), thereby enhancing local accumulation, improving the pathological follicular microenvironment associated with AGA, and promoting hair regrowth. Methods: QT nanocrystals (QT-NCs) were fabricated using a top–down wet media milling technique with GL as a bioactive stabilizer. The resulting QT-NCs were characterized regarding their particle size, crystallinity, morphology, and stability. The skin permeation properties of the QT-NCs were further evaluated in vitro, and their therapeutic efficacy was assessed in a dihydrotestosterone (DHT)-induced AGA mouse model. Results: The QT-NCs exhibited an irregular structure with a particle size ranging from 200 to 300 nm, demonstrating uniform dimensions and excellent storage stability. In vitro permeation studies revealed a 2.27-fold increase in cumulative penetration and a 2.47-fold enhancement in skin retention compared to raw QT. In the DHT-induced AGA mouse model, QT-NCs significantly reduced local DHT levels while concurrently modulating the follicular microenvironment, resulting in markedly improved therapeutic outcomes. Notably, when co-administered, QT and GL demonstrated synergistic pharmacological effects, suggesting potential combinatory benefits. Conclusions: This study presents the first demonstration of QT-NCs for AGA treatment, establishing a novel therapeutic strategy with substantial potential for clinical translation. Full article

Various signalling molecules and pathways critical for wool production and quality regulate wool secondary follicle (SF) development. Circular RNAs (circRNAs) regulate SF morphogenesis through a competing endogenous RNA (ceRNA) mechanism; these novel cyclic non-coding RNAs are not known to regulate the development of SFs in the foetal period of fine-wool sheep. Here, we analysed circRNA expression profiles in the foetal skin of Gansu Alpine fine-wool sheep at 10 developmental stages (E87, E90, E93, E96, E99, E102, E105, E108, E111, and E138) using RNA sequencing. Among the differentially expressed circRNAs (DE circRNAs), 173 were significantly enriched in signalling pathways related to hair follicle (HF) development, such as Wnt/β-catenin, transforming growth factor-β/Smad, Notch, and mitogen-activated protein kinase. Six HF-development-related circRNAs were expressed at different stages and potentially regulated SF development through the ceRNA network. In total, 16 DE circRNAs and their targets, 44 miRNAs, and 65 mRNAs were screened, and 88 ceRNA regulatory network pathways related to SF development were constructed. These key DE circRNAs could be candidate genes for further exploration of the molecular HF development mechanism, providing an important theoretical basis for unravelling the regulatory network of SF development in fine-wool sheep and genetic wool trait improvement. Full article

Fiber fineness is a critical determinant of wool quality and is of great significance in enhancing the overall quality of wool. The aim of this research was to pinpoint the key proteins that participate in the regulation of wool fineness. To achieve this, we utilized Astral—DIA proteomics technology to examine the disparities in proteins, pathways, and GO terms among the wool tissues of Gansu alpine fine-wool sheep with varying mean fiber diameters (MFD). The experiment was divided into two groups: coarse (group C, MFD = 22.36 ± 0.75 μm, n = 4) and fine (group F, MFD = 16.89 ± 0.36 μm, n = 4). The results indicated that 67 differentially expressed proteins (DEPs) were identified from the wool tissues of Gansu alpine fine-wool sheep in groups C and F. Functional enrichment analysis demonstrated that several key differential proteins, including MGST3, KRT26, KRT72, KRT74, KRT71, etc., were mainly enriched in multiple functional pathways. These pathways included glutathione metabolism, oxidative phosphorylation, the degradation of valine, leucine, and isoleucine, intermediate filaments, serine protease activity, and cysteine protease activity (p < 0.05). Furthermore, protein–protein interaction (PPI) network analysis suggested that type II keratin and type I keratin (such as CTSF, PSAP, TMEM106B, LYPD3, KRT71, KRT72), along with glutathione metabolism (MGST3, W5QDB7), are closely related to hair follicle development and the regulation of wool fineness. In summary, this study enriches the existing sheep proteinome database and offers novel perspectives on the regulatory mechanisms of wool fineness. Full article

Hair loss (alopecia) is a common disorder caused by an interruption in the body’s cycle of hair production. This pathology negatively affects the psychoemotional state of patients and significantly reduces their quality of life. The currently available medical treatments (including minoxidil therapy) are effective in arresting the progression of the disease; however, they allow only partial regrowth of hair at best. A significant clinical result occurs only with regular drug use. There is still great interest in finding new drugs for the treatment of alopecia. In this study, we aimed to examine the effect of an aqueous dispersion of unmodified fullerene C60 (ADF) on hair growth. ADF, produced by a unique technology, is biocompatible and non-toxic. Nu/nu mice were subcutaneously injected (2 μg/animal) every two days for a period of 11 days with ADF and, for control purposes, with phosphate-buffered saline (PBS). It was shown that ADF stimulated hair growth. Histological analysis of the nu/nu mice skin areas showed that animals treated with ADF had significantly more (about twice as many) hair follicles in the anagen phase compared to mice treated with PBS. The effect on hair growth persisted even after discontinuation of ADF administration. Analysis of gene expression demonstrated that ADF affected the Wnt-signaling pathway, increased the expression of the Wnt10b (wingless-type Mouse Mammary Tumor Virus integration site family, member 10B) factor, angiogenetic factors, and downregulated tumor necrosis factor-alpha levels. We propose that the mechanism of ADF action is likely related to its ability to attract macrophages to the hair follicle microenvironment and promote their polarization to the M2 phenotype. In addition, using molecular modeling, we tried to substantiate our hypothesis about the interaction of ADF with the adenosine A2A receptor, which may cause a decrease in tumor necrosis factor-alpha production. Thus, ADF may become a promising drug for the development of new approaches to the treatment of alopecia associated with immune disorders. Full article

Hair follicles are essential to hair formation and cyclic regeneration, experiencing growth and degeneration, and quiescence phases involving complex signaling pathways. Among these, fibroblast growth factors (FGFs) play a critical role in follicular morphogenesis, but the role of FGF receptor signaling in hair follicle development remains underexplored. Current treatments for hair loss, such as medical, surgical, light-based, and nutraceutical interventions, are often expensive, require long-term commitment, and are associated with substantial side effects. This review discusses the mechanisms and biological functions of the FGF signaling pathway within the hair follicle growth cycle, providing an overview of how these elements influence hair follicle dynamics and the pathogenesis of alopecia. Manipulating the FGF signaling pathway could offer new therapeutic options for androgenetic alopecia and other hair loss conditions, potentially exceeding current treatment modalities in efficacy and safety. Full article