A 31-year-old woman with a benign medical history presented with a beefy tongue and an erythematous rash. Evaluation revealed elevated urine glucose levels and the presence of a neuroendocrine tumor. A diagnosis of necrolytic migratory erythema associated with a neuroendocrine tumor was made.

Androgenetic alopecia (AGA), the most prevalent form of hair loss, is driven by progressive follicular miniaturization and dihydrotestosterone (DHT)-induced dysfunction of dermal papilla cells (DPCs). While oxidative stress is involved, the specific cell death modality and its upstream regulators remain poorly defined. Here, we demonstrate that ferroptosis-a regulated cell death process driven by iron-dependent lipid peroxidation-constitutes a key mechanism in DHT-induced DPC injury. Through structure-based molecular docking, we identified the natural flavonoid hispidulin as a novel agonist of the lysosomal cation channel TRPML1, a finding confirmed by cellular thermal shift assay (CETSA) and calcium imaging. In a DHT-induced mouse model of AGA, oral administration of hispidulin significantly promoted hair regeneration, restored anagen-phase follicular architecture, and upregulated crucial hair-growth factors (e.g., Ctnnb1, Vegf). Proteomic profiling and subsequent validation experiments revealed that hispidulin effectively suppressed ferroptosis in DPCs in vivo. Mechanistically, the therapeutic benefits of hispidulin, both in vivo and in vitro, were abolished by pharmacological inhibition (ML-SI3) or shRNA-mediated knockdown of TRPML1 (shTRPML1). Moreover, hispidulin-mediated restoration of DPC proliferative capacity and hair inductive function was completely reversed by the ferroptosis inducer Erastin. In summary, our work establishes TRPML1 as a crucial endogenous safeguard for DPC homeostasis, counteracting androgen-induced ferroptosis. Targeting the TRPML1-ferroptosis axis thus emerges as a promising therapeutic strategy for AGA, with hispidulin serving as a validated lead compound for this innovative approach.

In recent years, dermatoscopy has emerged as a valuable adjunctive tool for the diagnosis of various cutaneous disorders. Initially developed for the evaluation of melanocytic lesions, this non-invasive technique has since demonstrated significant utility in the assessment of non-melanocytic hyperpigmented dermatoses. This review provides an up-to-date and practical overview of the dermatoscopic manifestations of common non-melanocytic hyperpigmented conditions, including melasma, nevus of Ota, freckles, lentigines, solar lentigines, seborrheic keratosis, porokeratosis, acquired dermal macular hyperpigmentation, lichen planus-like keratosis, pigmented actinic keratosis, pigmented Bowen's disease, basal cell carcinoma, and acanthosis nigricans. Many of these hyperpigmented disorders exhibit distinct and characteristic dermatoscopic features. Given the clinical diagnostic challenges posed by these conditions and their significant psychological impact on patients, dermatoscopy offers a complementary approach to enhance the accuracy of evaluation and differential diagnosis.

Androgenetic alopecia (AGA) is a progressive hair loss disorder characterized by follicular miniaturization primarily driven by dihydrotestosterone (DHT). Mitochondrial dysfunction in dermal papilla cells (DPCs) has emerged as a key pathological feature, yet the upstream regulatory mechanisms remain unclear. Our previous work revealed that the mitochondria-targeted antioxidant MitoQ upregulates CYP19A1 (aromatase) and alleviates AGA-like pathology. Here, we investigated whether CYP19A1 modulates mitochondrial function and mediates the protective effects of MitoQ. Using a DHT-induced AGA mouse model and DPCs with CYP19A1 knockdown or overexpression, we examined hormone profiles, mitochondrial activity, and hair growth-related factors. DHT markedly reduced CYP19A1 expression and increased inhibitory factors such as DKK1, TGF-β, and IL-6, whereas CYP19A1 overexpression or MitoQ pretreatment reversed these effects. Both CYP19A1 and MitoQ decreased mitochondrial reactive oxygen species (mtROS), improved respiratory capacity, and preserved mitochondrial morphology. Importantly, our findings reveal a previously unrecognized aromatase-mitochondria cross-talk in hair-follicle cells, whereby CYP19A1-derived estrogens sustain mitochondrial homeostasis under androgenic stress. MitoQ amplifies this cross-talk through CYP19A1 activation, restoring redox balance and mitochondrial integrity. Collectively, these results identify CYP19A1 as a pivotal regulator of mitochondrial resilience and suggest that the CYP19A1-mitochondrial axis represents a promising pharmacological target for treating AGA.

The hair follicle microenvironment is the core functional unit of hair regeneration. dWAT (Dermal white adipose tissue) is an indispensable component of this microenvironment. Rather than serving as a passive filler, dWAT, through multidimensional mechanisms including cytokines, metabolites, extracellular vesicles, and cell-cell interactions, forms a complex regulatory network with local immune cells and exerts unique immune functions. It is deeply involved in the maintenance of local immune homeostasis, the regulation of the inflammatory response, and hair regeneration. In this review, we summarize the latest research on the effect of adipose-immune interactions on hair growth within the hair follicle microenvironment, focusing on how the dWAT surrounding the hair follicle serves as the foundation of the local adipose-immune interaction microenvironment, and on the regulatory mechanisms by which the immune function of hair follicle dWAT influences hair follicle regeneration. The dynamic remodeling of dWAT along the hair follicle cycle provides key metabolic support for the formation and regulation of the immune microenvironment around the hair follicle, and also constitutes the material basis for the crosstalk among immune cells within the hair follicle. The interaction between dWAT and immune cells affects the hair follicle growth process by regulating the local inflammatory response, immune cell phenotypic switching, and associated signaling pathways.

Androgenetic alopecia (AGA), a prevalent form of hair loss disorder, is pathologically characterized by dermal papilla cell (DPC) senescence driven by the dual pathogenic effects of excessive dihydrotestosterone accumulation and reactive-oxygen-species-mediated oxidative stress. Current clinical treatment strategies are challenged by poor hair follicle targeting, short retention times, and limited efficacy due to single-pathway interventions. To address these limitations, we developed a DPC-targeted, dual-functional finasteride/cerium oxide nanoparticle (L-LP-Fi/CeNP) drug delivery system designed to synergistically counteract DPC senescence through concurrent dihydrotestosterone inhibition and reactive oxygen species scavenging. By actively targeting the DPC-specific surface marker leptin receptor, this system notable enhanced cutaneous penetration depth and prolonged intrafollicular drug retention. Within the pathological microenvironment, the combined action of finasteride and CeNPs down-regulated senescence markers (p16/pRb) via dual-pathway synergy, effectively reversing cellular senescence and restoring the hair-inductive capacity of DPCs. In AGA mouse models, L-LP-Fi/CeNPs exhibited hair regenerative efficacy comparable to, and in some aspects modestly improved over, that of minoxidil, the current clinical standard treatment. This study presents a novel targeted therapeutic strategy combining small-molecule drug synergism with nanotechnology, which offers a promising prospect for AGA treatment.

INTRODUCTION:Alopecia areata is a prevalent autoimmune non-scarring alopecia with high post-treatment relapse and refractory rates, which severely impairs patients' physical and mental health. While CD8+ T cells are well-established as the primary effector cells in AA, emerging evidence indicates that dendritic cells (DCs) play important upstream regulatory roles in disease initiation and progression. AREAS COVERED:This narrative review systematically synthesizes relevant studies from the PubMed database published up to May 2026, dissecting the dual roles of distinct DC subsets in maintaining hair follicle immune privilege and driving autoimmune cascade, along with core molecular pathways. It also analyses DC-related mechanisms of standard therapies and emerging DC-targeted therapeutic strategies. EXPERT OPINION:DCs play important roles in the complex immunopathological network of AA. DC-targeted precision therapies hold substantial potential to overcome the limitations of broad immunosuppression and restore long-term follicular immune homeostasis, with single-cell multi-omics technologies enabling further mechanistic and translational advances.

BACKGROUND:The primary cause of alopecia areata (AA) is autoimmune-mediated hair follicle destruction, while breakdown of immune tolerance due to Treg cell homeostasis disruption critically contributes to this process. However, in AA, the factors leading to Treg cell impairment and the effective regulatory pathways remain unanswered. OBJECTIVES:To assess the therapeutic effects of sCD83 on AA and elucidate the crucial role of sCD83-mediated Treg cell activation in remodeling the perifollicular microenvironment. METHODS:Blood and scalp tissue were collected from AA patients and healthy controls to characterize sCD83 using ELISA, flow cytometry, and immunofluorescence. In graft-induced C3H/HeJ mouse model of AA, the therapeutic effect of sCD83 on early-onset AA was evaluated by H&E staining, immunofluorescence, and flow cytometry. In vitro, human hair follicle organ culture and primary outer root sheath keratinocyte (ORSK) culture were utilized to clarify the impact of sCD83 on the expression and activity of indoleamine 2,3-dioxygenase (IDO) in hair follicle. Co-culture of ORSKs and PBMCs, together with administration of an IDO inhibitor to AA mice, were performed to determine the necessity of IDO for Treg cell activation. Finally, GST-pulldown and co-IP assays were employed to identify potential sCD83 receptors on ORSKs. RESULTS:We showed here that AA patients exhibit sCD83 deficiency, which may be attributed to reduced sCD83 release from DCs, and that serum sCD83 levels are negatively correlated with disease severity. Supplementation with sCD83 in AA mouse reversed disease manifestations and promoted Treg cell proliferation. Mechanistically, IDO activity in ORSKs is essential for sCD83-mediated Treg cell activation, with TRX potentially serving as a sCD83 receptor to regulate IDO expression. CONCLUSIONS:Our study establish the functional role of sCD83 in AA, confirms the therapeutic potential of sCD83 supplementation, and provides some mechanistic insights.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune imbalance and excessive cytokine production, in which dysregulation of transient receptor potential vanilloid 4 (TRPV4) contributes to skin inflammation and itching. In this study, we screened a natural product library and identified sclareol as a preferential TRPV4 inhibitor. Molecular docking and calcium imaging in HaCaT cells confirmed that sclareol effectively blocks TRPV4 channel activation. With an MC903‑induced AD mouse model, we found that sclareol treatment significantly alleviated skin lesions, reduced epidermal thickening, decreased infiltration of CD4+ T cells, and lowered serum levels of immunoglobulin E (IgE), interleukin (IL)-1β, and IL-13. In an inflammatory cell model established by stimulating HaCaT cells with tumor necrosis factor (TNF)-α and interferon (IFN)-γ, sclareol attenuated the production of key inflammatory mediators, blocked activation of both NF‑κB and MAPK signaling pathways, and mitigated oxidative stress by reducing reactive oxygen species (ROS). To confirm target specificity, we used TRPV4‑knockout cells; notably, observed anti‑inflammatory and antioxidant effects were substantially attenuated in the absence of TRPV4. Collectively, this study establishes sclareol as a novel TRPV4 inhibitor that ameliorates AD pathology through a TRPV4‑dependent mechanism involving suppression of inflammatory signaling and oxidative stress.

Skin abscess is a common bacterial infection of the skin and soft tissues. Conventional treatment typically involves incision and drainage after pus formation, which may lead to prolonged healing and surgical scarring. Traditional Chinese Medicine (TCM) has extensive experience in treating infectious diseases with the potential for rapid recovery and minimal scarring; however, international literature on its efficacy remains limited. We present three cases of skin abscess successfully treated with an oral modified Xian Fang Huo Ming Yin (XFHMY) decoction based on syndrome differentiation. CASE 1: A 29-year-old male presented with a painful, swollen plaque on the left upper back persisting for over two weeks. CASE 2: A 12-year-old girl with a red, swollen mass on the left waist for more than 10 days. CASE 3: A 35-year-old male with a painful, erythematous plaque on the inner right upper arm for half a month. After 5-7 days of TCM treatment, all abscesses resolved completely without significant scarring, and only mild hyperpigmentation or depression remained. These findings suggest that TCM, particularly modified XFHMY, may serve as an effective non-invasive alternative therapy for skin abscesses.

BackgroundAlopecia areata (AA) is an autoimmune disease typified by nonscarring hair loss. It manifests as a heterogeneous disorder with diverse clinical presentations and variable treatment responses, underscoring the significance of identifying novel biomarkers for precision management.ObjectiveThis study aims to explore the relationship between metabolic reprogramming-related genes (MRRGs) and the risk of developing AA.MethodsMRRGs were identified through the GeneCards database and existing literature. Genetic instruments were obtained from the eQTLGen database, and AA-related data were retrieved from the OpenGWAS database. The TwoSampleMR R package was applied for statistical analysis. Additionally, RT-qPCR and immunofluorescence assays were performed to validate the expression of target genes in AA-affected hair follicles and healthy controls.ResultsSix MRRGs (DLD, NFE2L2, SDHB, SLC2A1, PSAT1, and SQSTM1) showed significant causal associations with AA. RT-qPCR analysis revealed markedly elevated SQSTM1 mRNA levels in AA-affected hair follicles compared with healthy controls. Immunofluorescence confirmed increased SQSTM1 protein accumulation alongside reduced LC3B-II expression in AA-affected hair follicles.ConclusionsThis study underscores the significant association between SQSTM1 and AA, advancing our understanding of AA pathophysiology.

BACKGROUND:Androgenetic alopecia (AGA) is one of the most common forms of hair loss, and recent studies suggest that dihydrotestosterone (DHT)-induced senescence of dermal papilla cells (DPCs) plays a crucial role in its pathogenesis. Clinically, we previously observed an overlap between areas exposed to ultraviolet (UV) radiation and regions affected by androgenetic hair loss. However, the relationship between UVA radiation and AGA onset remains unclear. Therefore, we aimed to investigate the role of UVA in intensifying DHT-induced hair loss, with focus on potential activation of cellular senescence pathways. METHODS:We used an AGA mouse model combined with UVA irradiation to examine the role of UVA in delaying DHT-induced hair growth. To further investigate the mechanisms of the interaction between DHT and UVA, we isolated human dermal papilla cells and performed transcriptome sequencing analysis. Senescence-associated β-galactosidase (SA-β-Gal) staining, quantitative PCR, and western blotting were used to assess senescence and autophagy. Rapamycin was tested in vivo for its ability to mitigate hair loss. RESULTS:UVA accelerated DHT-Induced hair growth delay in AGA mouse model. UVA exposure intensified DHT-induced cellular senescence in hDPCs. This process was associated with the activation of mTOR pathway. However, rapamycin alleviated UVA- and DHT-induced cellular senescence by modulating autophagy dysfunction. Furthermore, rapamycin effectively reversed UVA-exacerbated DHT-induced hair loss in AGA mouse model. CONCLUSION:UVA exposure can affect autophagy via the mTOR pathway, enhancing DHT-induced cellular senescence in DPCs. Rapamycin shows potential as a therapeutic agent to counteract these effects, offering a novel strategy for treating AGA.

Hair loss has long been a significant concern for many individuals. Recent studies have indicated that mitochondria play a more crucial role in hair loss than previously recognized. This review summarizes the connection between mitochondrial dysfunction and hair follicle development, outlines the links between diseases related to mitochondrial disorders and hair issues, and highlights the influence of mitochondrial dysfunction on androgenetic alopecia. We discuss the cellular and signaling mechanisms associated with hair loss and examine how mitochondrial dysfunction, such as insufficient energy supply, signaling irregularities, protein/gene abnormalities, and programmed cell death, can hinder the normal proliferation, differentiation, and growth of hair follicle cells. Furthermore, we discuss current treatment approaches and potential innovative therapies, including mitochondrion-targeting drugs and advanced techniques that directly target hair follicle cells, providing fresh insights into the crucial role of mitochondria in maintaining hair follicle health and managing hair disorders. Furthermore, this review explores future therapeutic strategies and proposes that mitochondrial research could lead to groundbreaking treatments for hair loss, thus providing optimism and new avenues for the treatment of individuals experiencing hair loss. This review not only underscores the central importance of mitochondria in hair health but also emphasizes the importance of advancing research and treatment in this field.

Oxidative stress plays a critical role in the pathogenesis of vitiligo by damaging keratinocytes, which disrupts their biological functions and influences the progression of the disease. MitoQ, a mitochondria-specific antioxidant, has the potential to prevent disorders associated with oxidative stress and to exert protective effects specifically on mitochondria. This study investigated the protective effects of MitoQ against oxidative stress in keratinocytes. We observed downregulated expression levels of Nrf2, PINK1, Parkin, and LC3 in vitiligo patients. HaCaT cells were treated with 900 μM H2O2 and/or 50 nM MitoQ, revealing that MitoQ mitigated the downregulation of Nrf2, PINK1, and Parkin; reduced the nuclear translocation of Nrf2; and decreased the level of mitophagy induced by H2O2. Following the knockdown of NFE2L2 or PINK1 in HaCaT cells, we noted an increase in intracellular reactive oxygen species, changes in mitochondrial morphology, a dramatic decrease in the mitochondrial membrane potential, and a significant rise in cell death levels. In comparison to the group without NFE2L2 or PINK1 knockdown, MitoQ treatment failed to alleviate these conditions. These results suggest that MitoQ may regulate the PINK1/Parkin signaling pathway via Nrf2 to counteract mitochondrial oxidative stress induced by H2O2 and protect cells from damage. Therefore, our study offers experimental evidence and insights that may inform the development of therapeutic interventions for vitiligo.

PURPOSE:Oxidative stress plays a significant role in the development of vitiligo. Although the specific mechanism of the mitochondria-targeted antioxidant mitoquinone (MitoQ) in vitiligo remains unclear, it has shown promise in the treatment of various diseases. METHODS:In this study, we employed network pharmacology, molecular docking, transcriptomic approaches, and experimental verification to investigate the potential targets of MitoQ in vitiligo. RESULTS:Molecular docking results identified four possible crucial targets of MitoQ in vitiligo treatment: poly (ADP-ribose) polymerase 1 (PARP1), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), and C-X-C motif chemokine receptor 3 (CXCR3). MitoQ alleviated oxidative stress-induced PARP1 nuclear mislocalization, attenuated ROS accumulation, restored mitochondrial membrane potential, and enhanced ATP synthesis in vitro analysis. Transcriptomic analysis demonstrated that MitoQ reduced the expression of DNA damage genes and genes involved in the PI3K-AKT and MAPK signaling pathways. The protein-protein interaction network indicated a potential relationship between PARP1 and DNA damage-related genes, suggesting that MitoQ could interfere with abnormal PARP1 activation. Notably, MitoQ reduced cellular senescence by decreasing CDKN1A/p21 protein through PARP1, and the knockdown of PARP1 reduced oxidative damage. CONCLUSION:These results indicate that PARP1 decreases cellular senescence and offers a potential target for therapeutic research in the management of vitiligo.

Vitiligo is the most common skin depigmentation disease, affecting 0.1%–2% of people in the world. 3.5%–20.5% of segmental patients account for the total number of vitiligo patients. It has been clinically observed that segmental vitiligo patients are more likely to generate white hair, which may be related to neuroendocrine factors. The color of human skin and hair is affected by the number and functional status of melanocytes. Vitiligo affects patients' physical and mental health due to the shame it causes from the white patches and hair. This article reviews the underlying mechanisms of segmental vitiligo with white hair based on skin and hair follicle melanocytes. The article attempts to propose possible targets for the treatment of this disease.

Post-inflammatory hyperpigmentation (PIH) is a common cosmetic concern, often leading to significant psychological distress for the patients. With the widespread application of lasers including ablative fractional resurfacing (AFR) with a 10,600 nm CO2 laser, PIH caused by lasers is becoming increasingly common. But due to the absence of an appropriate animal research model, our understanding of pathophysiological mechanisms and preventive strategies for PIH remains limited. This study aimed to establish an animal model to investigate PIH following AFR CO2 laser application, focusing on the dynamic changes in melanin, inflammatory cytokines, growth factors, and skin structures as PIH developed. We employed pigmented guinea pigs as our experimental subjects and conducted our research in two phases. In the first phase, we utilized three modes of AFR CO2 laser to identify which laser mode could induce PIH by monitoring dynamic melanin changes. In the second phase, the laser mode that most reliably induced PIH was applied to re-establish the PIH model. Pathophysiological changes during PIH progression were investigated through histopathological observations, real-time quantitative polymerase chain reaction, and two-photon microscopy. We successfully established a replicable animal model for PIH following AFR CO2 laser application. We observed a significant increase in inflammatory cytokines and growth factors within the skin tissue by the second week, with stable pigmentation becoming apparent by the third week. Our research provides a promising animal model for understanding and further investigating the mechanisms of PIH after laser procedures. V (animal study).