Cuiping Guan

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.

Vitiligo is a skin disorder marked by the loss of pigmentation due to melanocyte destruction. Our previous study demonstrated that DCUN1D1 is a novel regulator of CXCL10 and is associated with mitochondrial dysfunction. RNA‐seq data revealed that the expression of Parkin, a mitophagy‐related molecule, is decreased in vitiligo patients. Parkin functions as an E3 ubiquitin ligase. Based on these findings, we hypothesize that Parkin ubiquitinates DCUN1D1, thereby influencing the level of CXCL10 during the progression of vitiligo. Parkin and DCUN1D1 expression levels were assessed in both vitiligo patients and mice. To examine interactions, HaCaT cells were transfected with Flag‐ DCUN1D1 , Myc‐ PRKN , or HA‐ Ub , followed by coimmunoprecipitation (co‐IP) and Western blotting analysis. Mitochondrial activity and mitophagy were evaluated following various treatments, including the use of CCCP. HaCaT cells were transfected with DCUN1D1 or different concentrations of Parkin to assess CXCL10 levels. The supernatant from HaCaT cells was collected and incubated with melanocytes for 48 h, after which the apoptosis level was examined. DCUN1D1 was found to be upregulated, whereas Parkin was downregulated in both vitiligo patients and mice. Parkin interacts with DCUN1D1 and ubiquitinates it at lysine 27 (K27). Increased levels of Parkin counteract the reductions in mitochondrial activity and mitophagy induced by DCUN1D1, significantly downregulate CXCL10 levels, and reduce melanocyte apoptosis. This study provides evidence that Parkin‐mediated ubiquitination of DCUN1D1 regulates CXCL10 levels in vitiligo, thereby offering a new experimental foundation for understanding the pathogenesis of vitiligo.

Plant-derived exosome-like nanovesicles (PENs) are emerging as a unique class of bioactive nanocarriers with transformative potential in dermatology. Characterized by intrinsic biocompatibility, the ability to traverse biological barriers, and a molecular cargo rich in lipids, proteins, nucleic acids, and phytochemicals, PENs exert multi-target effects, including anti-inflammatory and antioxidant activities, modulation of melanogenesis, and promotion of tissue repair. In this review, we synthesize current advances in PEN biology, encompassing their biogenesis, molecular architecture, and cutting-edge methods for isolation, purification, and characterization. We also highlight translational progress in treating skin aging, alopecia, pigmentation disorders, and impaired wound healing, while critically addressing challenges that impede clinical adoption, such as toxicology, stability, delivery efficiency, manufacturing scalability, and regulatory compliance. By integrating mechanistic insights with translational strategies, PENs are poised to redefine therapeutic and cosmetic paradigms in skin health, offering a rare convergence of natural origin, molecular precision, and clinical promise.

NLRP3 functions as a critical intracellular danger sensor for inflammasome activation, playing a crucial role in autoimmune diseases. Vitiligo progression has been linked to NLRP3, yet its specific involvement in melanocytes of vitiligo remains poorly understood. In this study, we demonstrate that NLRP3 expression is significantly upregulated in the melanocytes of vitiligo patients and melanoma-Treg-induced vitiligo mouse model. Genetic knockout of NLRP3 effectively alleviates vitiligo progression in these mice. Our mechanistic investigations reveal that the downregulation of the E3 ligase β-TrCP1 in vitiligo melanocytes decreases K27-linked ubiquitination levels of NLRP3, which in turn weakens its interaction with the autophagy receptor NDP52. This disruption impairs the selective autophagic degradation of NLRP3, leading to hyperactivation of inflammation and pyroptosis in melanocytes, thereby accelerating vitiligo pathogenesis. Notably, melanocyte-specific knockdown of NLRP3 using lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos) carrying Nlrp3 shRNA significantly alleviates vitiligo development. This study elucidates the mechanism by which autophagy dysfunction mediated excessive NLRP3 inflammasome activation in melanocytes contributes to vitiligo pathogenesis, highlighting potential therapeutic strategies targeting these pathways for the treatment of vitiligo and other pigment-related skin diseases. Overview of disrupted NLRP3 autophagic degradation in vitiligo melanocytes. In healthy melanocytes, NLRP3 expression is upregulated when subjected to oxidative stress, along with an increase in the E3 ligase β-TrCP1, which enhances the K27-linked ubiquitination of NLRP3 and further strengthens its binding to the autophagy receptor protein NDP52, thus effectively suppressing the excessive inflammatory response. Whereas in the melanocytes of vitiligo patients, decreased expression of β-TrCP1 leads to downregulation of K27-linked ubiquitination in NLRP3, thus inhibiting its autophagic degradation. The persistent activation of NLRP3 in vitiligo melanocytes promotes the cleavage of pro-IL-1β and GSDMD. GSDMD-N subsequently forms pores on the cell membrane, which causes the release of IL-1β and results in melanocyte pyroptosis. In our study, we utilize KPV-Lipos with Nlrp3 shRNA to precisely knockdown NLRP3 expression in melanocytes and effectively alleviate vitiligo development, which provide a potentially promising strategy for the treatment of vitiligo. MC, melanocytes.

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.