Plasma-based approaches are attracting interest as potential anticancer strategies due to their ability to generate reactive species that damage tumor cells. However, clinical translation remains limited by challenges in biocompatibility, reproducibility, and chemical tunability. In this study, we utilized a nitrogen-oxygen gas mixture to generate a controllable spectrum of reactive species and evaluated its effects in endometrial (HEC1A), cervical (HeLa), melanoma (B16F10), and lung (H1299) cancer models. Nitrogen-oxygen plasma treatment preferentially reduced cancer cell viability compared to normal fibroblasts in vitro. Mechanistically, plasma exposure increased intracellular oxidative stress, and co-treatment with GSH attenuated cytotoxicity, indicating a central role for reactive species. Apoptosis was supported by Annexin V/PI staining, caspase-3 and PARP cleavage, mitochondrial depolarization, and increased γH2AX, phospho-p53, BiP, and CHOP. Transcriptomic profiling revealed activation of apoptotic pathways alongside modulation of ferroptosis-associated genes. Ferrostatin-1 partially rescued cell viability, linking cytotoxicity to lipid peroxidation, whereas iron chelation did not reduce lipid peroxidation. These findings indicate a contribution of lipid peroxidation without canonical iron-dependent ferroptosis. In vivo, treatment significantly suppressed tumor growth in a B16F10 melanoma allograft model following intratumoral administration. Together, these results demonstrate that nitrogen-oxygen plasma induces apoptosis with additional oxidative lipid damage, supporting its therapeutic potential.

BACKGROUND Stasis dermatitis is a chronic inflammatory dermatosis secondary to chronic venous insufficiency. Treatment of refractory cases remains challenging. High-molecular-weight non-crosslinked hyaluronic acid (HMWNCHA) combined with succinic acid (SA) possesses anti-inflammatory and regenerative properties. We report 2 septuagenarian patients with refractory stasis dermatitis and psychosocial deterioration treated with intradermal HMWNCHA plus SA. CASE REPORT Case 1 involved a 77-year-old man with chronic venous insufficiency and refractory stasis dermatitis associated with severe symptoms, impaired mobility, and psychosocial deterioration. After failure of conventional therapies, he received 2 sessions of intradermal HMWNCHA plus SA administered 1 month apart, resulting in marked and sustained clinical and psychosocial improvement at 6-month follow-up. Case 2 involved a 75-year-old woman with refractory unilateral stasis dermatitis secondary to chronic venous insufficiency. Following the same treatment protocol, substantial improvement was observed after the first session, with near-complete lesion resolution after the second session and sustained remission at 6-month follow-up. No treatment-related adverse effects were reported. CONCLUSIONS In these 2 patients with refractory stasis dermatitis, intradermal HMWNCHA plus SA was associated with marked and sustained clinical improvements and enhanced quality of life. Further studies are warranted to confirm these findings.

Zinc is essential for skin homeostasis, yet the identity and function of zinc-rich epidermal cells remain poorly defined. MT1 (metallothionein-1), a zinc-responsive protein, is commonly used as an intracellular zinc marker, but whether MT1+ cells represent epidermal stem cells or specialized populations is unclear. In this study, we generated an Mt1-P2A-EGFP-2A-CreERT knock-in mouse model enabling lineage tracing of MT1+ cells. Reporter activation confirmed zinc-dependent expression and revealed that MT1+ cells are broadly distributed across the interfollicular epidermis, lower junctional zone, and hair follicles from embryonic stages through adulthood. Single-cell RNA sequencing identified MT1+ cells as a distinct cluster with minimal overlap with established epidermal stem cell markers, indicating that MT1 does not define a canonical stem cell population but instead marks a heterogeneous subset of epidermal cells. Lineage tracing during homeostasis showed contributions to multiple epidermal lineages, including sebaceous glands and isthmus regions. However, during wound healing, MT1+ cells exhibited limited migration or participation in regeneration, whereas MT1- cells primarily drove epidermal repair and follicle reformation. These findings suggest that MT1 marks zinc-associated epidermal cells involved in maintenance rather than regeneration and reveals heterogeneity within zinc-responsive epidermal populations, highlighting distinct roles for MT1+ and MT1- cells in skin physiology and repair.

Cell-derived nanovesicles are emerging as versatile carriers for therapeutic delivery, but their surface charge and protein corona critically influence their biological behavior. Here, plasma coating is introduced as a rapid, tunable, and reagent-free strategy to transiently modify vesicle surface properties. Plasma exposure reverses the membrane charge of cell membrane-derived nanovesicles in a treatment time-dependent and reversible manner. Moreover, plasma treatment modulates the density and composition of the protein corona, yielding a profile associated with reduced immune recognition and enhanced cellular interaction. These changes collectively improve cellular uptake, drug delivery efficiency, and therapeutic activity in vivo. This controllable and biocompatible surface-engineering approach offers a scalable platform for optimizing nanovesicle-based drug delivery and related biomedical applications.

Droplet evaporation on thin substrates is crucial in basic and applied physics, especially for emerging technologies using thin films and inkjet printing in flexible electronics. We experimentally investigate how substrate thickness influences droplet evaporation across different materials. Using fast X-ray microtomography, we visualize droplet dynamics on thin polymer membranes and find that substrate deformation has negligible effects. Instead, evaporation slows as substrate thickness decreases, indicating that heat transfer plays a dominant role. Infrared thermal imaging shows that temperature differences across substrates increase logarithmically with thickness, confirming reduced heat transfer in thinner substrates. Our results show that increasing the polymer substrate thickness from 1 to 8 mm enhances the heat transfer rate by 7.4 times, resulting in a 1.3 times increase in the evaporation rate constant. These findings highlight the practical significance of substrate thinning in linking droplet evaporation and heat transfer, which is critical for thin-film applications.

Abstract Zinc (Zn²⁺) is an essential trace element that supports a vast array of cellular processes, including enzymatic catalysis, gene expression, immune regulation and signaling. Its unique redox-inert properties and ability to bind diverse proteins make it indispensable for cellular homeostasis. Zinc is dynamically distributed within cells, where its compartmentalization across organelles, such as the nucleus, endoplasmic reticulum, Golgi apparatus, mitochondria, lysosomes, endosomes and peroxisomes, enables specialized functions crucial for organelle integrity and interorganelle communication. The present Review provides a comprehensive account of organelle-specific zinc homeostasis, highlighting the intricate roles of zinc transporters, metallothioneins and metallochaperones in regulating zinc flux and buffering. Here we discuss how zinc modulates structural and enzymatic processes, stress responses, redox balance and signaling pathways within each organelle. We then provide an integrated overview of how its dysregulation contributes to diverse molecular dysfunctions and pathologies including neurodegeneration, cancer, metabolic disorders and aging. We further examine emerging therapeutic strategies aimed at restoring zinc homeostasis, including supplementation and bioengineered, organelle-targeted delivery systems, as well as advanced tools for visualizing zinc dynamics at subcellular resolution. Together, these insights demonstrate the crucial role of zinc as a compartmentalized regulator of cellular health and a promising target for therapeutic intervention.

Background:Thread lifting has emerged as a minimally invasive alternative to surgical facial rejuvenation, providing mechanical tissue repositioning with shorter recovery times. Advances in biomaterials and thread design have improved safety and lifting capacity; however, variability in clinical outcomes persists due to differences in vector design, thread type, tissue manipulation, and anesthesia techniques. These factors may influence complication rates, procedural tolerance, and postoperative downtime, contributing to ongoing concerns regarding the predictability and reproducibility of thread-lifting procedures. Objective:To describe the development of a vector-optimized thread-lifting technique (VectorLift) and to compare its clinical performance in an exploratory, real-world, non-randomized comparative study with two commonly used thread-lifting approaches employing different biomaterials and insertion methods. Methods:The VectorLift protocol was developed using anatomically guided vector placement, ligament-oriented reinforcement, and optimized local anesthetic infiltration. Over a three-year period, 44 female patients (mean age 47 years) underwent facial thread-lifting procedures. Eighteen patients were treated using the proposed technique with cannulated polydioxanone (PDO) threads, while the remaining patients were treated with either double-needle poly-L-lactic acid (PLA) plus poly(L-lactide-co-glycolide) (PLGA) cone threads or cannulated PLA/polycaprolactone (PCL) threads. Clinical outcomes included recovery time (days of downtime), intraoperative pain levels, patient satisfaction measured using the FACE-Q scale before treatment and two weeks post-procedure, and complication rates including dimpling, bruising, edema, and transient asymmetry. Standardized clinical photographs were obtained before and immediately after treatment. Results:VectorLift was associated with lower reported intraoperative pain, shorter recovery time and lower rates of early postoperative complications compared with the other techniques, while patient satisfaction scores were comparable among groups. Immediate photographic assessment confirmed visible aesthetic improvement without overcorrection. Conclusion:VectorLift is an anatomically guided thread-lifting technique that, in this real-world non-randomized comparative study, was associated with improved procedural tolerance and shorter postoperative downtime while maintaining high patient satisfaction and effective aesthetic outcomes. Further controlled studies with larger patient populations and longer follow-up periods are warranted to confirm these findings.

Golgi abnormalities have been linked to aging and age-related diseases, yet the underlying causes and functional consequences remain poorly understood. This study identifies the interaction between age-associated zinc deficiency and Golgi stress as a critical factor in cellular aging. Senescent Golgi bodies from human fibroblasts show a fragmented Golgi structure, associated with a decreased interaction of the zinc-dependent Golgi-stacking protein complex Golgin45-GRASP55. Golgi stress is increased, and functions such as glycosylation and vesicle transport are impaired. These disturbances promote Golgi and perinuclear microtubule disassembly and subsequent mislocalization of intracellular proteins associated with cellular signaling and epigenetic control. Pharmacological induction of Golgi stress or zinc deficiency, or ablation of the Golgi-associated zinc transporter gene Zip13 in mouse fibroblasts, replicate the characteristics of cellular senescence, emphasizing the critical role of Golgi-zinc homeostasis. These findings highlight the importance of adequate zinc intake and suggest targeting Golgi dysfunction as a therapeutic strategy for alleviating age-related cellular decline.

Background: Polydeoxyribonucleotide (PDRN) is increasingly used in dermatology and cosmetic applications owing to its regenerative and anti-aging properties. However, its topical use is limited by its high molecular weight and anionic charge, which restrict skin penetration. Methods: In this study, we employed a nitrogen-oxygen plasma treatment to PDRN to overcome these limitations and characterized its physicochemical properties and in vitro efficiency. Results: Upon plasma treatment, PDRN’s surface charge was attenuated and its hydrodynamic size decreased, leading to improved uptake and markedly increased cell migration activity. Conclusions: These findings suggest that plasma treatment can transform PDRN into a cosmetically viable active ingredient and may provide a general strategy for adapting other high-molecular-weight bioactives for topical delivery.

Thin film deposition is essential in the cosmetic industry, where formulations such as foundations and concealers rely on uniform layer formation to conceal pores and texture irregularities for a natural and even appearance. However, variations in skin topography, influenced by factors such as aging, genetics, and environmental exposure, can significantly affect the behavior of these films. Aging, in particular, leads to increased skin roughness and wrinkles, creating challenges to achieve consistent cosmetic deposition in diverse age groups. This study investigates the impact of age-related topographical changes on cosmetic thin film deposition and introduces a model for standardized, age-specific evaluation of cosmetic performance. Using X-ray microtomography, we compare skin topography from a cohort of the Korean population segmented into young and aged groups. A PDMS-based model is then constructed using these skin topographies, and thin film deposition is assessed both on human-derived skin positives and on the assembled model. This approach demonstrates the potential of artificial skin models for the precise quantification and evaluation of film coverage. In addition, we propose an improved model that incorporates key factors such as skin porosity and sebum production to increase realism. By exploring the interactions between skin morphology and cosmetic behavior, this method offers valuable insights into optimizing formulations to meet the diverse needs of consumers.

Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field.

Although sucrose is not detected in human body fluids and cells, putative sucrose transporters are conserved. They are classified as the SLC45A family, which is constituted by 4 members, namely SLC45A1, 2, 3, and 4 (Vitavska and Wieczorek, 2013). These proteins show high topological resemblance and amino acid sequence similarity with the plant sucrose/H+ transporter SUCs (Supplementary Figure S1). They also conserve the plant sucrose transporter motif, a GRRRPFI sequence between the transmembrane domains II and III (Supplementary Figure S2a and b).

Zinc is an important trace mineral in the human body and a daily intake of zinc is required to maintain a healthy status. Over the past decades, zinc has been used in formulating topical and systemic therapies for various skin disorders owing to its wound healing and antimicrobial properties. Zinc transporters play a major role in maintaining the integrity of the integumentary system by controlling zinc homeostasis within dermal layers. Mutations and abnormal function of zinc-transporting proteins can lead to disease development, such as spondylocheirodysplastic Ehlers–Danlos syndrome (SCD-EDS) and acrodermatitis enteropathica (AE) which can be fatal if left untreated. This review discusses the layers of the skin, the importance of zinc and zinc transporters in each layer, and the various skin disorders caused by zinc deficiency, in addition to zinc-containing compounds used for treating different skin disorders and skin protection.

Spermidine (SPD), a polyamine naturally present in living organisms, is known to prolong the lifespan of animals. In this study, the role of SPD in melanogenesis was investigated, showing potential as a pigmenting agent. SPD treatment increased melanin production in melanocytes in a dose dependent manner. Computational analysis with RNA-sequencing data revealed the alteration of protein degradation by SPD treatment without changes in the expressions of melanogenesis-related genes. Indeed, SPD treatment significantly increased the stabilities of tyrosinase-related protein (TRP)-1 and -2 while inhibiting ubiquitination, which was confirmed by treatment of proteasome inhibitor MG132. Inhibition of protein synthesis by cycloheximide (CHX) showed that SPD treatment increased the resistance of TRP-1 and TRP-2 to protein degradation. To identify the proteins involved in SPD transportation in melanocytes, the expression of several solute carrier (SLC) membrane transporters was assessed and, among 27 transporter genes, SLC3A2, SLC7A1, SLC18B1, and SLC22A18 were highly expressed, implying they are putative SPD transporters in melanocytes. Furthermore, SLC7A1 and SLC22A18 were downregulated by SPD treatment, indicating their active involvement in polyamine homeostasis. Finally, we applied SPD to a human skin equivalent and observed elevated melanin production. Our results identify SPD as a potential natural product to alleviate hypopigmentation.

BACKGROUND:Nicotinamide mononucleotide (NMN) is a representative anti-aging drug that, after long-term administration in mice, causes an increase in energy and lipid metabolism, improves eye function, immune response, and increases insulin sensitivity. However, the effects of NMN on skin pigmentation are still unknown. OBJECTIVE:In this study, we aimed to demonstrate the effects of NMN on melanogenesis. METHODS:NMN was applied to both young and aged melanocytes, and melanin production, protein expression, and mRNA levels were analyzed. A reconstituted human skin model was used to validate the effect of NMN on melanogenesis in vivo. RESULTS:NMN treatment showed no apparent effects on young melanocytes, however, in aged melanocytes, a marked reduction in melanin production was observed. NMN treatment also efficiently reduced melanin production in a reconstituted human skin with aged melanocytes. Genome-wide analysis showed the downregulation of melanogenesis-related cyclic adenosine monophosphate (cAMP)/Wnt signaling in aged melanocytes. Moreover, NMN treatment downregulated forskolin-induced expression of melanogenesis-related proteins, tyrosinase (TYR), tyrosinase-related protein (TRP)- 1, and TRP-2. Nicotinamide adenine dinucleotide (NAD+), an NMN product within the cells, also reduced cAMP/Wnt signaling in aged melanocytes. SLC12A6 was the most highly expressed gene among the SLC12A family members in melanocytes and was significantly influenced by NMN or NAD+ treatment, indicating that SLC12A6 protein is an NMN transporter in melanocytes. CONCLUSION:NMN reduces melanogenesis in aged melanocytes by downregulating the signaling of melanogenesis-associated receptors. Therefore, NMN is a human-friendly anti-melanogenic agent with the potential to aid in aging-related hyperpigmentation therapy.

Background:Hyperactivated airway mucosa cells overproduce mucin and cause severe breathing complications. Here, we aimed to identify the effects of saponins derived from Panax ginseng on inflammation and mucin overproduction. Methods:NCI-H292 cells were pre-incubated with 16 saponins derived from P. ginseng, and mucin overproduction was induced by treatment with phorbol 12-myristate 13-acetate (PMA). Mucin protein MUC5AC was quantified by enzyme-linked immunosorbent assay, and mRNA levels were analyzed using quantitative polymerase chain reaction (qPCR). Moreover, we performed a transcriptome analysis of PMA-treated NCI-H292 cells in the absence or presence of Rg5, and differential gene expression was confirmed using qPCR. Phosphorylation levels of signaling molecules, and the abundance of lipid droplets, were measured by western blotting, flow cytometry, and confocal microscopy. Results:Ginsenoside Rg5 effectively reduced MUC5AC secretion and decreased MUC5AC mRNA levels. A systematic functional network analysis revealed that Rg5 upregulated cholesterol and glycerolipid metabolism, resulting in the production of lipid droplets to clear reactive oxygen species (ROS), and modulated the mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathways to regulate inflammatory responses. Rg5 induced the accumulation of lipid droplets and decreased cellular ROS levels, and N-acetyl-l-cysteine, a ROS inhibitor, reduced MUC5AC secretion via Rg5. Furthermore, Rg5 hampered the phosphorylation of extracellular signal-regulated kinase and p38 proteins, affecting the NF-κB signaling pathway and pro-inflammatory responses. Conclusion:Rg5 alleviated inflammatory responses by reducing mucin secretion and promoting lipid droplet-mediated ROS clearance. Therefore, Rg5 may have potential as a therapeutic agent to alleviate respiratory disorders caused by hyperactivation of mucosa cells.

Mesenchymal stem cells (MSCs) are multipotent stem cells derived from adult stem cells. Primary MSCs can be obtained from diverse sources, including bone marrow, adipose tissue, and umbilical cord blood. Recently, MSCs have been recognized as therapeutic agents for skin regeneration and rejuvenation. The skin can be damaged by wounds, caused by cutting or breaking of the tissue, and burns. Moreover, skin aging is a process that occurs naturally but can be worsened by environmental pollution, exposure to ultraviolet radiation, alcohol consumption, tobacco use, and undernourishment. MSCs have healing capacities that can be applied in damaged and aged skin. In skin regeneration, MSCs increase cell proliferation and neovascularization, and decrease inflammation in skin injury lesions. In skin rejuvenation, MSCs lead to production of collagen and elastic fibers, inhibition of metalloproteinase activation, and promote protection from ultraviolet radiation-induced senescence. In this review, we focus on how MSCs and MSC-derived molecules improve diseased and aged skin. Additionally, we emphasize that induced pluripotent stem cell (iPSC)-derived MSCs are potentially advanced MSCs, which are suitable for cell therapy.

Natural killer (NK) cells are lymphocytes that can directly destroy cancer cells. When NK cells are activated, CD56 and CD107a markers are able to recognize cancer cells and release perforin and granzyme B proteins that induce apoptosis in the targeted cells. In this study, we focused on the role of phytoncides in activating NK cells and promoting anticancer effects. We tested the effects of several phytoncide compounds on NK-92mi cells and demonstrated that α-pinene treatment exhibited higher anticancer effects, as observed by the increased levels of perforin, granzyme B, CD56 and CD107a. Furthermore, α-pinene treatment in NK-92mi cells increased NK cell cytotoxicity in two different cell lines, and immunoblot assays revealed that the ERK/AKT pathway is involved in NK cell cytotoxicity in response to phytoncides. Furthermore, CT-26 colon cancer cells were allografted subcutaneously into BALB/c mice, and α-pinene treatment then inhibited allografted tumor growth. Our findings demonstrate that α-pinene activates NK cells and increases NK cell cytotoxicity, suggesting it is a potential compound for cancer immunotherapy.