Search Results (87)

Androgen dysregulation impairs the homeostasis of the prostate, hair follicles, and ovaries, driving the pathogenesis of prostate cancer (PCa), benign prostatic hyperplasia (BPH), androgenetic alopecia (AGA), and polycystic ovary syndrome (PCOS). Current antiandrogen therapies are constrained by drug resistance, off-target toxicity, and limited long-term efficacy. Plant extracts, enriched with bioactive constituents such as polyphenols, alkaloids, and flavonoids, represent promising multi-target candidates. Therefore, focusing on plant extracts—particularly those of dietary origin—this review summarized the mechanisms by which they regulate androgen-dependent and androgen-independent signaling pathways, and recent advances in nutritional interventions targeting androgen-responsive organs. Furthermore, it discussed the multi-component combined effects and factors affecting in vivo exposure of plant extracts, including metabolic transformation and tissue distribution, which may influence the anti-androgenic activity. In summary, anti-androgenic plant extracts primarily target androgen synthesis and AR signaling across various androgen disorder models, with crosstalk into cell growth and cycle, anti-inflammatory pathways, and regulation of growth factors. This multi-target regulation relies on the mixture effects of plant extracts. Future research should focus on three directions: extract standardization, clinical validation, and advanced delivery systems. Full article

Liaoning cashmere goat is a unique Chinese cashmere breed, and skin fibroblast proliferation determines hair follicle development and cashmere quality. Melatonin regulates cutaneous cell activity, and lncRNAs function as ceRNA to sponge miRNAs and modulate target genes. Whether melatonin controls fibroblast proliferation through an lncRNA-miRNA-mRNA cascade remains unclear. This study explored how melatonin mediates the LncRNA16913.1-chi-miR-195-5p-FZD6 axis to regulate cashmere goat skin fibroblast proliferation. We constructed gain-of-function and loss-of-function models of LncRNA16913.1 and chi-miR-195-5p. Immunohistochemistry located FZD6 in hair follicles; RT-qPCR, Western blot, CCK-8, EdU and flow cytometry detected gene expression and cell phenotypes. Bioinformatic prediction, dual-luciferase assay, fluorescence in situ hybridization, RNA pull-down and rescue tests verified molecular binding relationships. Melatonin upregulated LncRNA16913.1 and FZD6, yet downregulated chi-miR-195-5p, with FZD6 mainly distributed in hair follicle inner and outer root sheaths. Inhibiting chi-miR-195-5p boosted fibroblast proliferation, restrained apoptosis and accelerated the cell cycle. chi-miR-195-5p directly suppressed FZD6, while cytoplasmic LncRNA16913.1 sequestered this miRNA to recover FZD6 expression. Silencing LncRNA16913.1 eliminated melatonin-mediated FZD6 upregulation. In short, melatonin increased LncRNA16913.1, which sequestered chi-miR-195-5p to release FZD6 and facilitate fibro-blast proliferation. Combined dual-luciferase, bidirectional rescue and cellular phenotypic assays collectively verified the fact that FZD6 acts as the functional downstream target of chi-miR-195-5p to mediate fibroblast proliferation in vitro. Full article

The cashmere fibers produced by the secondary hair follicles of cashmere goats are precious textile raw materials. The secondary hair follicles exhibit a distinct annual cyclical pattern, comprising anagen, catagen, and telogen phases. Although a large amount of skin transcriptome data is currently available for cashmere goats, this study aims to systematically investigate the regulatory factors controlling the cyclical dynamics of secondary hair follicles through re-analysis of these data. Skin transcriptome data of Inner Mongolian cashmere goats were downloaded from the Sequence Read Archive (SRA) database. Bioinformatics analyses, including quality control, read mapping, quantification, differential expression analysis, Gene Ontology (GO) enrichment analysis, and KEGG pathway analysis, were performed to identify key regulatory genes governing the secondary hair follicle cycle. The results revealed a total of 1232 differentially expressed genes (DEGs) from comparisons across different phases. KEGG pathway analysis identified three signaling pathways associated with cashmere development: the cAMP signaling pathway (chx04024), the relaxin signaling pathway (chx04926), and the estrogen signaling pathway (chx04915). GO analysis yielded 335 terms, of which 236 were statistically significant (P-adj < 0.05). The DEGs were predominantly involved in biological processes such as regulation of transcription by RNA polymerase II, proteolysis, and positive regulation of transcription by RNA polymerase II. Significantly enriched cellular components included the plasma membrane, membrane, and extracellular space, and molecular functions were mainly related to protein binding, identical protein binding, and DNA-binding transcription factor activity, RNA polymerase II-specific. Based on their expression patterns, five key genes were selected: KRT25, KRT39, MAPK12, SPP1, and TCHHL1. These genes displayed significantly distinct expression profiles across the hair follicle cycle. TCHHL1 exhibited the highest expression in anagen, intermediate expression in catagen, and the lowest expression in telogen, with significant differences among all three phases. MAPK12 was specifically upregulated in telogen and was significantly more highly expressed than in both anagen and catagen. SPP1 showed high expression in anagen and catagen but extremely low expression in telogen. KRT39 displayed significantly higher expression in both anagen and catagen compared to telogen. KRT25 reached its highest expression in catagen, which was significantly different from that in telogen, while its expression in anagen showed no significant difference from either telogen or catagen. This study characterized the regulatory genes of the secondary hair follicle cycle in cashmere goats at the transcriptional level and analyzed the association between their expression patterns and cycle regulation. Full article

Skin and its appendages form an integrated system of ectodermal mini-organs that rely on Wnt signaling for lifelong homeostasis and regeneration; yet, the pathway operates in a highly organ-specific manner in each compartment. In interfollicular epidermis, the Wnt activity is spatially graded, thus maintaining the balance between basal progenitor proliferation and terminal differentiation. The hair follicle is governed by an intrinsic oscillator based on cross-regulation between Wnt and BMP signaling, providing a cell-autonomous layer of control over hair cycle dynamics. Finally, the nail organ is characterized by the spatial compartmentalization of Wnt activity, with a distal matrix activation zone supported by specialized mesenchymal niche cells that sustain continuous nail plate growth and coordinate the digit tip regeneration. Understanding these divergent regulatory architectures provides a conceptual framework for targeted regenerative strategies aimed at enhancing repair in skin and its appendages. Therefore, in this review, we synthesize recent molecular studies on Wnt signaling in the adult skin, hair follicles, and nail mini-organs, highlighting appendage-specific features that underlie their distinct regenerative capacities. We further discuss how dysregulated Wnt signaling contributes to skin, hair, and nail pathologies such as alopecia, chronic wounds, excessive scarring, skin cancer, and nail deformations, and summarize the emerging strategies that target Wnt pathway to therapeutically enhance hair regrowth, wound repair, cancer treatment, and digit tip regeneration. Full article

Hair follicles are highly specialized mini-organs within the skin that drive the production of wool and cashmere, traits of major biological and economic importance in sheep and goats. Despite their microscopic size, hair follicles exhibit extraordinary regulatory complexity, integrating genetic programs with seasonal, endocrine, environmental, and epigenetic cues. Although transcriptional networks and signaling pathways underlying follicle morphogenesis and cycling have been extensively investigated, the post-transcriptional mechanisms that fine-tune these processes remain insufficiently understood. MicroRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators that coordinate cell fate determination, lineage commitment, and tissue homeostasis. Growing evidence indicates that miRNAs play essential roles in hair follicle stem cell maintenance, proliferation, differentiation, apoptosis, and organ-level development, functioning through interconnected regulatory networks rather than isolated linear pathways. By modulating the expression of key follicle-determining genes and signaling components, miRNA-mediated regulation shapes follicle formation, cyclic regeneration, and fiber traits. In this review, we synthesize recent advances in miRNA research related to hair follicle biology, with a particular focus on wool- and cashmere-bearing mammals. We integrate findings across species to propose a systems-level framework in which miRNA networks interface with canonical signaling pathways and epigenetic mechanisms to orchestrate follicle development and regeneration. Conserved and species-specific regulatory principles are discussed to bridge fundamental follicle biology with practical applications in fiber production. Overall, this review highlights miRNAs as a critical yet previously underappreciated regulatory layer in hair follicle biology. A deeper understanding of miRNA-mediated control provides new conceptual insights into wool and cashmere development and offers a foundation for future molecular breeding and precision regulation strategies in livestock. Full article

Dynamic changes in gene and transcript expression represent a key factor in regulating the cyclical development of hair follicles. In this study, based on Nanopore sequencing (ONT-seq) data of skin tissue from three developmental stages (anagen (An), catagen (Cn), and telogen (Tn)) of Jiangnan cashmere goat hair follicles, this study presents a profile of candidate DETs implicated in cycle regulation by delineating their stage-specific expression patterns and dynamic expression trends from anagen to telogen. A large proportion of the candidate DETs were significantly enriched in functions related to fat synthesis, storage, or metabolism, with significance levels of p < 0.05 or p < 0.01. These significantly enriched DETs, which were generally upregulated from An to Cn or downregulated from Cn to Tn, support a model where accelerated intradermal fat deposition promotes the progression from An to Cn, while its subsequent decrease facilitates the transition from Cn to Tn. Concurrently, our results also suggest a potential role for dynamic changes in AS patterns in regulating the hair follicle cycle. This regulatory role of AS patterns is potentially mediated through affecting genes related to lipid synthesis/metabolism or cell structure/interaction. Notably, a broader range of fat synthesis, storage, or metabolism-related transcripts showed significant differential expression (p < 0.05) in the An vs. Cn group. Ultimately, by establishing this candidate DET profile, we aim to provide fresh perspectives for deciphering the complex molecular regulation of the hair follicle cycle and to identify new targets for genetically enhancing or molecularly breeding cashmere traits in cashmere goats. Full article

Cashmere goats produce high-value fine fibers derived from secondary hair follicles; however, the molecular mechanisms underlying this trait remain incompletely understood. In this study, comparative transcriptome sequencing was performed on skin tissues from Inner Mongolian cashmere goats and normal goats to characterize gene expression differences associated with cashmere fiber production. High-quality RNA-seq data with strong mapping efficiency and reproducibility were obtained across all samples. Differential expression analysis identified 1543 significantly differentially expressed genes (DEGs) between cashmere and normal goats, including genes involved in hair follicle morphogenesis, epidermal differentiation, cell proliferation, and extracellular matrix organization. Multivariate analyses showed a clear transcriptomic separation between fleece types, indicating that fleece phenotype is the primary driver of variation in global gene expression. Functional enrichment revealed significant involvement of the Wnt, MAPK, and PI3K–Akt signaling pathways, and several biologically relevant regulators of hair follicle development and hair cycle control, including FGF5, SOX9, LHX2, and VDR, were differentially expressed. Gene fusion events were rare and showed no group specific patterns, whereas alternative splicing was widespread, with exon skipping as the predominant splicing event in goat skin. Overall, these results provide quantitative transcriptomic evidence linking signaling regulation, follicle development, and structural differentiation to secondary hair follicle activity and cashmere fiber formation, offering candidate genes and molecular pathways for functional validation and molecular breeding in cashmere goats. Full article

Melatonin, an indoleamine crucial for regulating circadian rhythms, sleep–wake cycles, and immune–endocrine homeostasis, is present in biological fluids at extremely low concentrations, making its quantification analytically challenging. This narrative review provides a critical comparative assessment of current methodologies for melatonin determination across various biological matrices—plasma, urine, saliva, breast milk, and hair. The discussed techniques include immunoassays, colorimetric and spectrophotometric methods, chromatographic–mass spectrometric platforms (LC–MS/MS, UHPLC–MS/MS), and emerging biosensors. Each approach is evaluated regarding analytical sensitivity, specificity, reproducibility, cost, and clinical applicability. While immunoenzymatic and colorimetric techniques offer accessible, low-cost solutions for large-scale or preliminary studies, LC–MS/MS remains the benchmark for reference analysis, providing sub-picogram detection limits and multiplexing capability. However, its high cost, procedural complexity, and inter-laboratory variability limit routine implementation. New developments, including molecularly imprinted polymers, dispersive microextraction, and nanomaterial-based biosensors, suggest a shift toward hybrid, sustainable, and portable analytical platforms. By synthesizing recent methodological advances and identifying key limitations, this review aims to guide researchers and clinicians in selecting the most appropriate analytical approach for clinical, pharmacological, and circadian biomonitoring applications. Full article

Male pattern baldness (MPB) is a highly prevalent condition with a complex, poorly understood molecular basis that limits therapeutic innovation. This study aimed to bridge the gap between statistical genetic associations and biological function by identifying and prioritizing causal proteins and pathways involved in MPB. Using data from 24,069 men in the UK Biobank, we performed a proteome-wide association study of 2911 plasma proteins with self-reported MPB severity via multivariable ordinal logistic regression, adjusting for age, Body Mass Index (BMI), ethnicity, lifestyle, socioeconomic factors, and testosterone levels. Significant proteins underwent pathway enrichment analysis. Genetic integration included MAGMA for gene-level aggregation and tissue prioritization, transcriptome-wide association studies (TWAS) with GTEx models, conditional fine-mapping, and validation in an independent scalp biopsy transcriptomics dataset (GSE90594). Druggability and pleiotropy were evaluated using databases and phenome-wide association studies. Forty-seven proteins were significantly associated with MPB severity, enriched in pathways involving epidermis development, hair cycle regulation, and cell adhesion. Multi-omic integration prioritized five independent candidate genes: CD38, FGF5, TACSTD2, DPEP1, and PLB1. Transcriptomic validation confirmed differential expression in balding scalp for CD38 (upregulated) and TACSTD2, PLB1 (downregulated). CD38 was identified as druggable with low pleiotropic risks. This study elucidates the molecular architecture of MPB, revealing novel biological pathways beyond canonical androgen signaling. By prioritizing promising non-hormonal targets like CD38, our findings provide a robust, evidence-based framework to guide the development of future therapeutic interventions for this common condition. Full article

This study systematically measured gross hair weight and hair length traits across five body regions of 759 Tianzhu White Yak individuals. The BSL trait exhibited moderate heritability, while the BL trait demonstrated high heritability (h² = 0.450). All other traits showed low heritability. GWASs were conducted using whole-genome resequencing data comprising 22,566,255 high-quality SNP loci. The MLM model identified 519 genome-wide significant loci and 767 chromosome-wide significant loci. Chromosome 6 harbored the highest number of significant SNP loci, while the remaining significant loci were distributed across multiple autosomes. Strong long-range linkage disequilibrium (r² > 0.7) was observed between numerous significant SNPs on chromosome 6 associated with Gw and HL traits. A total of 73 candidate genes were annotated, including FGF5, CFAP299, and PRDM8. Functional enrichment analysis based on the GO and KEGG databases revealed significant enrichment in cytoplasm and the MAPK signaling pathway. Sanger sequencing results revealed that mutations in the FGF5, CFAP299, PRDM8, ANTXR2, and GPHB5 genes significantly affected the Gw, HL, and BSL traits of Tianzhu White Yak (p < 0.01). Linkage disequilibrium analysis indicated strong linkage disequilibrium (r² > 0.6) among Sanger-sequenced SNP loci on the same chromosome. From a biological perspective, multiple candidate genes such as FGF5 and CFAP299 are involved in hair follicle cycle regulation, cell proliferation, and metabolic control, suggesting its potential role in hair follicle development and hair shaft growth. This study identifies candidate loci and genes for gross hair weight and hair length traits in Tianzhu White Yak, contributing to elucidating the genetic mechanisms underlying hair production performance. Full article

Androgenetic alopecia (AGA) and telogen effluvium (TE) are common hair loss disorders characterized by dysregulated hair follicle cycling and impaired dermal papilla cell function. Emerging evidence indicates that exosomes are key mediators of intercellular communication, largely through their microRNA (miRNA) cargo. Milk-derived exosomes (Mi-Exos) represent an accessible and biologically active source of regulatory miRNAs with potential relevance for hair disorders. This study evaluated the in vitro effects of bovine milk-derived exosomes (MEV-miRNAs) on human hair follicles. MEV-miRNAs were enriched in miRNA families (Let-7, miR-21, miR-30, miR-200, and miR-148/152) previously implicated in hair follicle regulation. Viability/metabolic activity of hair follicle dermal papilla (HFDP) cells was assessed, and human hair follicles were cultured ex vivo to measure shaft elongation and modulation of the WNT signaling pathway by qRT-PCR. MEV-miRNAs significantly increased HFDP cell viability after 24 h compared with controls. Human hair follicles showed a non-significant trend toward increased elongation following treatment. Gene expression analysis revealed significant up-regulation of key WNT pathway components, including WNT2, WNT5B, WNT10A, WNT11, MMP7, WISP1, and NKD1, indicating modulation of WNT-associated pathways implicated in hair follicle growth and cycling. Overall, MEV-miRNAs exhibit positive modulatory effects on signaling pathways, supporting their potential as a novel therapeutic strategy for AGA and TE. Full article

Exosomes are small extracellular vesicles that package DNA fragments, several classes of RNA, lipids, and proteins, and are now regarded as active messengers between cells rather than as cellular debris. This narrative review synthesizes dermatologic and related regenerative applications reported between 2020 and 2025, drawing on PubMed and Scopus searches. In skin, exosomes regulate inflammation, angiogenesis, matrix remodeling, pigmentation, and hair cycling. Preclinical models show faster wound closure, improved scar architecture, attenuation of photoaging changes, and stimulation of hair growth, with additional signals in inflammatory dermatoses and fungal skin disease. Early human studies in wound care, rejuvenation, scars, and alopecia suggest acceptable safety and a recurring pattern of benefit when exosomes are used as adjuncts to microneedling, lasers, or standard dressings, although products, dosing, and outcome measures remain heterogeneous. Beyond dermatology, early work in osteoarticular and soft tissue repair points toward meaningful regenerative potential, but clinical programs are still at an early stage. In practice, exosomes are being positioned as acellular alternatives or add-ons to platelet-rich plasma, bone marrow aspirate concentrate, and conventional topicals and as emerging carriers for small molecules and biologics. Key limitations include low yields, product and cargo heterogeneity, lack of agreed quality and potency metrics, and uncertain regulatory status. Whether exosomes remain boutique adjuncts or become part of standard dermatologic and musculoskeletal practice will depend on what happens next: consistent manufacturing, agreed-upon characterization panels, meaningful potency assays, robust pharmacokinetic and biodistribution data, and comparative trials that track outcomes and safety over years rather than weeks. Full article

Platycladus orientalis exhibits significant potential as an antioxidant, anti-inflammatory, and hair growth-promoting ingredient, while the low bioavailability of raw Platycladus orientalis leaves extracts limits their further application. In this study, yeast fermentation was employed to prepare Platycladus orientalis Leaves Yeast Fermented Solution (PYFS). Its performance on human dermal papilla cells (HDPCs) was systematically investigated. The optimal fermentation strain was screened using the methyl thiazolyl tetrazolium (MTT) assay, and Saccharomycopsis fibuligera CICC33226 (SF) was identified as the most suitable strain for fermentation. The effects of PYFS on the cell cycle distribution, growth factors, inflammatory factors of HDPCs, as well as its hair growth-promoting mechanism, were investigated. Experiments revealed that after fermentation, the proportion of cells in the G0/G1 phase decreased by 11.09%, while the proportion of cells in the S phase increased by 35.44%. Additionally, the level of the growth factor VEGF increased by 42.34%, while the level of the inflammatory factor TGF-β1 decreased by 23.81%. Moreover, the fermentation process correlates with altered mRNA expression of Wnt/β-catenin pathway-related genes by upregulating the mRNA expression levels of β-catenin, DVL1, and LEF1, and downregulating the mRNA expression level of DKK-1. Finally, non-targeted metabolomics technology was used to analyze the metabolite changes after fermentation. The most significant differential metabolites mainly include flavonoids, amino acids and their derivatives, and organic acids and their derivatives. This study utilized microbial fermentation technology to prepare the yeast fermentation solution, selected the optimal fermentation strain, and demonstrated that its fermentation product significantly promotes HDPC metabolic activity, supports hair follicle health by regulating the balance of growth factors, alters expression patterns of Wnt/β-catenin pathway-related genes, and substantially alters the metabolite composition of Platycladus orientalis leaves extract through fermentation. Full article

Protein S-palmitoylation is a pivotal yet poorly integrated research field in dermatology. This reversible post-translational lipid modification primarily occurs on cysteine residues and is principally catalyzed by zinc finger and Asp-His-His-Cys DHHC-domain containing proteins (zDHHCs). The S-palmitoylation/depalmitoylation cycle directly affects protein localization, trafficking, stability, and protein–protein interaction, thereby regulating a variety of signaling pathways, including those mediating inflammation and immune reaction. Accumulating evidence has indicated that S-palmitoylation regulates various skin biological functions, including skin inflammation, skin barrier function, hair growth, and melanin synthesis, and is ultimately implicated in the initiation and development of massive dermatoses, such as alopecia and psoriasis. The recent development of new research tools, coupled with S-palmitoylation’s therapeutic potential, makes the timely synthesis of its role in skin pathophysiology both critical and opportune. Here, we summarize recent advances in understanding the mechanistic roles of S-palmitoylation in dermatological conditions and evaluate its potential as a therapeutic target for innovative treatment strategies. Full article

Hair growth is orchestrated by a complex cycle comprising the anagen, catagen, telogen, and exogen phases that are largely regulated by dermal papilla cells (DPCs). The disruption of oxidative balance and inflammation impairs follicle function and regeneration. Fermented yeast complex extract (FYCE) is a bioactive material derived from enzymatically hydrolyzed yeast and collagen substrates through a two-step fermentation with Lactobacillus brevis and Lactobacillus plantarum, enriched in antioxidant amino acids such as γ-aminobutyric acid (GABA) and L-alanine. In this study, we evaluated the effect of FYCE on hair regrowth, with a focus on its modulation of oxidative stress and inflammatory pathways in hydrogen peroxide (H₂O₂)-treated DPCs. FYCE treatment significantly enhanced NRF2 expression (3.2-fold compared to H₂O₂-treated DPCs), a central transcription factor controlling antioxidant defense, and concomitantly suppressed NF-κB activity (0.6-fold compared to H₂O₂-treated DPCs), a key mediator of inflammation. Importantly, FYCE also attenuated the activation of the NLRP3 inflammasome, as evidenced by the decreased expression levels of its molecular components. Complementary studies showed that FYCE increased IGF-1 (5.4-fold compared to H₂O₂-treated DPCs), Wnt10b (1.8-fold compared to H₂O₂-treated DPCs), and Wnt3a (2.9-fold compared to H₂O₂-treated DPCs), and stabilized β-catenin (2.8-fold compared to H₂O₂-treated DPCs). FYCE also showed these changes in the shaved animal skin, which was associated with increased hair follicle number (1.6-fold compared to the water-administered control group) and the anagen phase (3.0-fold compared to the water-administered control group). Collectively, our results suggest that FYCE promotes hair regrowth through the dual modulation of antioxidative and anti-inflammatory pathways, specifically by activating NRF2, inhibiting NF-κB signaling, and downregulating the NLRP3 inflammasome. These findings support FYCE as a promising candidate for further investigation as a treatment to prevent or reverse hair loss, with in vivo and clinical studies substantiating its efficacy and safety. Full article