Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by intense pruritus, eczematous lesions, and significant impairment of quality of life. In severe or chronic cases, AD can present with diverse atypical phenotypes, among which prurigo nodularis (PN)-like lesions are clinically challenging due to their recalcitrance to conventional therapies. Patients with severe AD are also at an increased risk of comorbid immune-mediated diseases, such as alopecia areata (AA), a non-scarring hair loss disorder driven by aberrant immune responses. Ivarmacitinib, a highly selective oral Janus kinase 1 (JAK1) inhibitor, has been approved by the National Medical Products Administration (NMPA) of China for moderate-to-severe atopic dermatitis (April 2025) and alopecia areata (June 2025). Herein, we report a case of a 28-year-old male patient with a long-standing history of AD who developed generalized PN-like lesions and concurrent AA (with a 2-year disease duration) and androgenetic alopecia (AGA). Conventional therapies including topical corticosteroids and antihistamines failed to yield satisfactory outcomes. Following treatment with ivarmacitinib (8 mg once daily), the patient showed rapid improvements in skin lesions, pruritus, and hair regrowth. This case suggests that ivarmacitinib may be beneficial for complex AD phenotypes with comorbid immune-mediated hair loss.

This study aimed to optimize the extraction and purification of TSG-enriched Polygonum multiflorum extract and evaluate its therapeutic potential against androgenetic alopecia. P. multiflorum Thunb. has long been used in traditional Chinese medicine to promote hair growth and preserve hair pigmentation. Microwave-assisted extraction (MAE) was optimized to obtain a 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG)-enriched P. multiflorum extract (PME). The crude extract was further purified by medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography. Phytochemical profiling by HPLC demonstrated a 3.75-fold increase in TSG content, from 22,770.0 ± 815 ppm to 85,387.5 ± 192 ppm, and the identity of the enriched TSG was confirmed by LC-MS and [1]H NMR spectroscopy. PME exhibited potent dose-dependent inhibition of 5α-reductase activity, reaching 92.7% inhibition at 1 μg/mL, comparable to that of finasteride. In a testosterone (TES)-induced androgenetic alopecia (AGA) mouse model, PME markedly accelerated hair regrowth and increased both the number and size of hair follicles. Mechanistically, PME suppressed the conversion of TES to dihydrotestosterone (DHT) through 5α-reductase inhibition and promoted GSK3β inactivation, β-catenin stabilization, and nuclear translocation, indicating activation of the Wnt/β-catenin signaling pathway. Consequently, the expression of hair growth-related proteins, including Ki67 (1.98-fold), epidermal growth factor (EGF, 1.54-fold), insulin-like growth factor-1 (IGF-1, 1.21-fold), and vascular endothelial growth factor (VEGF, 1.34-fold), was significantly upregulated. These findings demonstrate, for the first time, that TSG-enriched PME obtained through optimized MAE and chromatographic purification promotes hair regeneration through a dual mechanism involving 5α-reductase inhibition and Wnt/β-catenin activation, highlighting its potential as a natural therapeutic candidate for androgenetic alopecia.

Androgenetic alopecia (AGA) is a common form of hair loss with limited treatment options, driven by poorly understood molecular mechanisms. Using single-cell RNA sequencing of human scalp follicles from balding and non-balding regions, we constructed a high-resolution molecular anatomy atlas of the hair follicle and its microenvironment. We identified significant silencing of Wingless-related integration site 5A (WNT5A) signaling, which was widely known as the trigger of non-canonical WNT signaling pathway, in hair follicle stem cells (HFSCs) from balding areas, leading to downregulation of the transcription factor ATF3 and its target FOSB. Therapeutically, functional validation showed that activating the WNT5A-ATF3-FOSB axis maintained HFSC competence in AGA murine models and significantly inhibited the progression of AGA. Our findings reveal a critical molecular axis in AGA pathogenesis, highlighting its potential as a therapeutic target for hair loss disorders.

Diffuse unpatterned alopecia (DUPA) is an uncommon and incompletely characterized variant of androgenetic alopecia (AGA) marked by diffuse follicular miniaturization across the entire scalp, including the occipital region, which distinguishes it from classic patterned AGA and often precludes hair transplantation.

Androgenetic alopecia (AGA) is a common form of hair loss due to genetic factors and is associated with alterations in the scalp microenvironment, which contribute to hair follicle miniaturization. In this study, we investigated the effects of tolerogenic dendritic cell (tolDC)-conditioned medium (CM) in a dihydrotestosterone (DHT)-treated mouse model. Administration of tolDC-CM promoted hair regrowth in the dorsal skin of mice and was associated with modulation of the follicular microenvironment. TolDC-CM treatment reduced pro-inflammatory cytokine expression and increased anti-inflammatory cytokine levels in the dorsal skin of mice. Histological analysis further demonstrated increased dermal thickness and hair follicle regeneration following tolDC-CM treatment. Furthermore, tolDC-CM treatment modulated the Wnt/β-catenin and MAPK/NF-κB signaling pathways. In addition, tolDC-CM with TGF-β neutralization suppressed hair regrowth in a DHT-treated mouse model, supporting the involvement of microenvironmental regulation. These results suggest that tolDC-CM may represent a potential approach for AGA, targeting the microenvironment to restore hair growth by modulating the follicular microenvironment.

Androgenetic alopecia (AGA) is the most common type of hair loss worldwide, characterized by progressive miniaturization of hair follicles and a shortened anagen phase. Currently, FDA-approved drugs for AGA treatment, minoxidil and finasteride, cannot provide satisfactory outcomes for all patients and can sometimes cause side effects. Therefore, there has been an urgent need for novel and safer therapeutic strategies. At the cellular and molecular level, the pathogenesis of AGA is closely associated with the dysregulation of signaling pathways in hair follicles. As nano-sized extracellular vesicles secreted by cells, exosomes carry bioactive substances such as proteins, lipids, and nucleic acids, thereby playing a crucial role in intercellular and intracellular communication. By modulating dysregulated signaling pathways in hair follicles, exosome therapy offers a highly promising therapeutic option for AGA patients. However, it should be noted that current evidence remains limited, and more well-designed studies are required to validate the long-term efficacy and safety of exosome-based therapies for AGA. Also, addressing challenges in the production, application, and regulation of exosomes is indispensable for promoting the future clinical application of exosome-based therapies in AGA treatment. This review summarizes the preclinical and clinical progress in exosome-based therapies for AGA treatment, with a particular focus on their molecular mechanisms, especially their regulation of key signaling pathways involved in AGA pathogenesis, such as Wnt/β-catenin, Shh, TGF-β/Smad, PI3K/AKT, and MAPK signaling pathways. These endeavors are expected to provide researchers with valuable scientific insights and practical information for AGA drug discovery.

Androgenetic alopecia (AGA) is the most common cause of non-scarring hair loss in men. Although topical minoxidil and oral finasteride are established treatments, some patients show limited clinical response despite prolonged therapy. Evidence on the use of oral bicalutamide in male AGA remains scarce because of concerns about systemic adverse effects. We report the case of a 45-year-old man with treatment-resistant AGA who experienced clinically apparent hair regrowth during oral bicalutamide exposure after an inadequate response to conventional therapies. Treatment was accompanied by gynecomastia, mastodynia, decreased libido, erectile dysfunction, and mild elevations in hepatic enzymes, leading to drug discontinuation. Clinical adverse effects resolved after withdrawal of bicalutamide; however, follow-up hormonal evaluation and liver function tests were unavailable. This case describes a temporal association between androgen receptor blockade, clinically apparent hair regrowth, and clinically significant adverse effects. Although the findings provide additional insight into the role of androgen receptor signaling in AGA, they should not be interpreted as evidence supporting the use of oral bicalutamide in male patients. Further controlled studies are needed to better define the safety profile and potential role of androgen receptor antagonism in androgenetic alopecia.