Search Results (59)

Skin aging is closely related to mitochondrial dysfunction and cell cycle abnormalities, and developing intervention strategies targeting mitochondrial quality control is an important direction for anti-aging research. In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated β-galactosidase (SA-β-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control. Full article

Alopecia, a prevalent dermatological disorder affecting over half of the global population, is strongly associated with psychological distress. Extracts from Periplaneta americana (L. PA), a medicinal insect resource, exhibit pharmacological activities (e.g., antioxidant, anti-inflammatory, microcirculation improvement) that align with core therapeutic targets for alopecia. This study aimed to systematically investigate the efficacy and mechanisms of PA extracts in promoting hair regeneration. A strategy combining network pharmacology prediction and in vivo experiments was adopted. The efficacy of a Periplaneta americana extract was validated by evaluating hair regrowth status and skin pathological staining in C57BL/6J mice. Transcriptomics, metabolomics, RT-qPCR, and 16s rRNA techniques were integrated to dissect the underlying mechanisms of its hair-growth-promoting effects. PA-011 significantly promoted hair regeneration in depilated mice via multiple mechanisms: enhanced skin superoxide dismutase activity and upregulated vascular endothelial growth factor expression; modulated FOXO/PI3K/AKT signaling pathway and restored skin microbiota homeostasis; and accelerated transition of hair follicles from the telogen to anagen phase. PA-011 exerts hair-promoting effects through synergistic modulation of FOXO/PI3K/AKT signaling and the skin microbiome. As a novel therapeutic candidate, it warrants further systematic investigation for clinical translation. Full article

The human skin microbiota, a complex community of bacterial, fungal, and viral organisms, plays a crucial role in maintaining skin homeostasis and regulating host-pathogen interactions. Dysbiosis within this microbial ecosystem has been implicated in various dermatological conditions, including acne vulgaris, psoriasis, seborrheic dermatitis, and atopic dermatitis. This review, for the first time, provides recent advancements in all four layers of omic technologies—metagenomics, metatranscriptomics, metaproteomics, and metabolomics—offering comprehensive insights into microbial diversity, in the context of functional skin modeling. Thus, this review explores the application of these omic tools to in vitro skin models, providing an integrated framework for understanding the molecular mechanisms underlying skin–microbiota interactions in both healthy and pathological contexts. We highlight the importance of developing advanced in vitro skin models, including the integration of immune components and endothelial cells, to accurately replicate the cutaneous microenvironment. Moreover, we discuss the potential of these models to identify novel therapeutic targets, enabling the design of personalized treatments aimed at restoring microbial balance, reinforcing the skin barrier, and modulating inflammation. As the field progresses, the incorporation of multi-omic approaches into skin-microbiome research will be pivotal in unraveling the complex interactions between host and microbiota, ultimately advancing therapeutic strategies for skin-related diseases. Full article

Autoimmune CD8⁺ T cell-driven melanocyte destruction constitutes a key pathogenic mechanism in the development of vitiligo. Therefore, the pharmacological inhibition of CD8⁺ T cell effector functions and skin trafficking is a clinically viable therapeutic strategy. This study investigates leflunomide (LEF), an immunomodulatory drug with established safety in autoimmune diseases, for its therapeutic potential in a tyrosine-related protein (TRP) 2-180-induced vitiligo mouse model. Through flow cytometry, immunofluorescence, ELISA, and histopathological analyses, we systematically evaluated LEF’s effects on T cell regulation, chemokine expression, and cytokine profiles. Key findings demonstrated that LEF (20 mg/kg/day) significantly attenuated depigmentation by reducing CD8⁺ T cell infiltration and suppressing the IFN-γ-driven expression of CXCL9/10. Furthermore, LEF restored CD4⁺/CD8⁺ T cell homeostasis and rebalanced pro-inflammatory (IFN-γ, TNF-α, IL-2) and anti-inflammatory (IL-4, IL-10) cytokines, inducing a shift from Th1 to Th2. These results position LEF as an effective immunomodulator that disrupts the IFN-γ-CXCL9/10 axis and re-establishes immune balance, offering a promising repurposing strategy for halting vitiligo progression. Full article

Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms. Full article

Skin aging is driven by cellular senescence, oxidative stress, and diminished regenerative capacity. In this study, we investigated the effects of PhytoCellTec™ Argan, an argan callus extract (PC), on primary human fibroblasts and adult stem cells. PC treatment (0.1% and 0.5%) significantly enhanced fibroblast proliferation, reduced senescence-associated β-galactosidase activity, and decreased the expression of p16, p21, and phosphorylated NFκB. PC treatment lowered intracellular ROS levels, increased ATP production, and promoted autophagy via LC3B-II accumulation and p62 reduction. In skin-derived precursor cells (SKPs), as well as mesenchymal stem cells (MSCs), PC treatment improved spheroid formation and growth while preserving the expression of key stemness markers, including Sox2, Oct4, and Nestin. Furthermore, PC exhibited antioxidant capacity (TEAC assay) and inhibited elastase, supporting its anti-aging potential. These findings suggest that PC is safe at concentrations below 1% and may serve as an effective natural compound to restore cellular homeostasis, reduce senescence and inflammation, and support stem cell health during aging. Full article

Systemic sclerosis (SSc) is an autoimmune fibrotic disorder affecting the skin and internal organs, categorized as either limited cutaneous SSc, where distal areas of skin are involved, or diffuse cutaneous SSc, where more extensive proximal skin involvement is seen. Vascular remodelling and internal organ involvement are frequent complications in both subsets. Multiple pathogenic mechanisms have been demonstrated, including production of disease-specific autoantibodies, endothelial cell damage at an early stage, infiltration of involved tissues by immune cells, as well as environmental factors triggering the onset such as solvents and viruses. Although not strongly familial, susceptibility to SSc is associated with multiple single nucleotide polymorphisms in immunoregulatory genes relevant to antigen presentation, T cell signalling and adaptive immunity, as well as innate immunity. In addition, several lines of evidence demonstrate abnormalities within the epithelial cell layer in SSc. Macroscopically, the SSc epidermis is pigmented, thickened and stiff and strongly promotes myofibroblasts in co-culture. Moreover, multiple activating factors and pathways have been implicated in the disease epidermis, including wound healing responses, induction of damage associated molecular patterns (DAMPS) and the release of pro-fibrotic growth factors and cytokines. Similar to SSc, data from studies of cutaneous wound healing indicate a major role for epidermal keratinocytes in regulating local fibroblast responses during repair of the wound defect. Since the epithelium is strongly exposed to environmental factors and richly populated with protective immune cells, it is possible that disease-initiating mechanisms in SSc involve dysregulated immunity and tissue repair within this cell layer. Treatments designed to restore epithelial homeostasis or else disrupt epithelial–fibroblast cross-talk could be of benefit in this severe and resistant disease. Accordingly, single cell analysis has confirmed an active signature in SSc keratinocytes, which was partially reversed following a period of JAK inhibitor therapy. Full article

Vitamin D, a hormone synthesized in the skin through ultraviolet B radiation (UVB), plays a crucial role not only in calcium and phosphate homeostasis but also in regulating skin homeostasis and modulating immune responses. In keratinocytes, vitamin D is converted to its active form, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D), which interacts with the vitamin D receptor (VDR) to regulate gene expression involved in proliferation, differentiation, and antimicrobial defense. Dysregulation of this pathway has been implicated in inflammatory skin diseases such as psoriasis, atopic dermatitis, acne vulgaris, and hidradenitis suppurativa. These conditions are associated with altered epidermal differentiation, immune imbalance, and microbial interactions, where vitamin D plays a modulatory role by suppressing proinflammatory cytokines, enhancing antimicrobial peptide synthesis, and restoring skin barrier integrity. Topical vitamin D analogues have shown therapeutic benefits in psoriasis, while emerging evidence supports the adjunctive role of vitamin D supplementation in acne, hidradenitis suppurativa, and atopic dermatitis. Despite promising associations between low serum vitamin D levels and disease severity, a causal relationship remains uncertain. This review integrates molecular mechanisms with clinical findings, emphasizing the role of vitamin D in cutaneous physiology and pathology, and highlights the need for further research into targeted supplementation strategies in dermatological disorders. Full article

Sleep deprivation is a prevalent issue that disrupts the circadian rhythm of estrogen, particularly estradiol, thereby significantly affecting women’s skin health and appearance. These disruptions can impair skin barrier functionality and decrease dermal collagen synthesis. In this study, our results demonstrate that topical taurine supplementation promotes the expression of tight junction (TJ)-related proteins and enhances collagen production, effectively restoring skin homeostasis in sleep-deprived female mice. Mechanistically, taurine upregulates the expression of TMEM38B, a gene encoding the TRIC-B trimeric cation channel, resulting in increased intracellular calcium ion levels. This, in turn, promotes the upregulation of TJ-related proteins, such as ZO-1, occludin, and claudin-11 in epidermal cells, while also enhancing the expression of type III collagen in fibroblasts, thus restoring skin homeostasis. These findings suggest that taurine may serve as an alternative to estradiol, effectively improving skin homeostasis disrupted by sleep deprivation while mitigating the potential risks associated with exogenous estrogen supplementation. Collectively, these results provide preliminary insights into the protective mechanisms of taurine against sleep deprivation-induced skin impairments and establish a foundation for its potential application in treating skin conditions related to estrogen imbalances, such as skin aging in menopausal women. Full article

Recent studies have emphasized the impact of gut microbiota on skin health, but the reverse, how skin diseases affect gut homeostasis, has received less attention. Allergic contact dermatitis (ACD), a common skin disorder affecting one in four people worldwide, can be accompanied by intestinal disturbances. To explore this, we used an experimental model of ACD to investigate the intestinal changes induced by the disease. Parameters assessed included intestinal microbiota, short-chain fatty acids (SCFAs), gene expression related to intestinal permeability, inflammatory cytokines, and mucus production. To evaluate potential therapeutic interventions, the probiotic Bifidobacterium longum strain BB536 was administered via gavage, starting 10 days before dermatitis induction and continuing until the last day of disease induction. ACD caused alterations in the composition of intestinal microbiota compared to naïve mice but did not affect SCFA production. The probiotic altered microbiota composition and increased acetate production in dermatitis-induced mice. ACD decreased the gene expression of TjP1, ATHO1, and MUC2, while probiotic treatment restored TjP1 and ATHO1 to normal levels. The cytokine IL-6 increased in the ACD group compared to naïve mice, whereas IL-10 decreased; probiotic treatment also restored these levels. Intestinal mucus production, affected by ACD, was partially restored by probiotic treatment. The findings suggest that probiotics could be a therapeutic strategy to prevent intestinal issues caused by skin diseases. Full article

The decline in autophagy disrupts homeostasis in skin cells, leading to oxidative stress, energy deficiency, and inflammation—all key contributors to skin photoaging. Consequently, activating autophagy has become a focal strategy for delaying skin photoaging. Natural plants are rich in functional molecules and widely used in the development of anti-photoaging cosmetics. Hedyotis diffusa (HD), as a medicinal plant, is renowned for its anti-inflammatory and anticancer properties; however, its effects on skin photoaging remain unclear. This study investigates HD’s potential to counteract skin photoaging by restoring mitochondrial autophagy in keratinocytes. We used HPLC to detect the main chemical components in HD and, using a UVB-induced photoaging model in HaCaT keratinocytes, examined the effects of HD on reactive oxygen species (ROS) levels, Ca²⁺ concentration, mitochondrial membrane potential (MMP), apoptosis, and the cell cycle. Cellular respiration was further evaluated with the Seahorse XFp Analyzer, and RT-PCR and Western blotting were used to analyze the impact of HD on mitochondrial autophagy-related gene expression and signaling pathways. Our findings indicate that HD promotes autophagy by modulating the PI3K/AKT/mTOR and PINK/PARK2 pathways, which stabilizes mitochondrial quality, maintains MMP and Ca²⁺ balance, and reduces cytochrome c release. These effects relieve cell cycle arrest and prevent apoptosis associated with an increased BAX/BCL-2 ratio. Thus, HD holds promise as an effective anti-photoaging ingredient with potential applications in the development of cosmetic products. Full article

Sirtuins are a family of lysine deacetylases that regulate cellular homeostasis and energy sensing. Regeneration is the process that restores structural and functional homeostasis at the cellular, tissue, organ, and appendage levels. Several cellular processes, such as epithelial–mesenchymal transition (EMT), proliferation, migration, and differentiation, contribute to restoration after an injury. This review highlights the role of sirtuins in tissue, organ, and anatomical structure regeneration, showing how sirtuins modulate signalling pathways by deacetylating targets such as transcription factors. Furthermore, understanding the role of this protein family could help elucidate the molecular and cellular mechanisms underlying tissue regeneration, which may hold significant potential for fields such as regenerative medicine. The review compiles evidence suggesting that sirtuins are emerging factors in the regeneration of various organs (e.g., skin, liver, heart) and tissues (e.g., bone, muscle, cornea, spinal cord). Full article

Seborrheic dermatitis (SD) is a chronic inflammatory skin disease that primarily affects sebaceous-rich areas such as the scalp, face, and upper trunk. While the precise etiology remains multifactorial, the role of the skin microbiome, particularly the proliferation of Malassezia species, and alterations in the skin barrier function are critical in its pathogenesis. Disruption of the skin barrier, characterized by increased transepidermal water loss (TEWL) and reduced production of epidermal lipids, creates a favorable environment for microbial overgrowth and inflammation. Recent insights highlight the interplay between the impaired barrier function, immune responses, and the skin microbiome in perpetuating the disease. Additionally, novel dermocosmetic approaches are emerging that target these underlying mechanisms, offering promising therapeutic avenues. This review provides a comprehensive overview of the involvement of skin microbiome and barrier dysfunction in seborrheic dermatitis and discusses the potential of advanced dermocosmetic treatments aimed at restoring skin homeostasis and preventing disease recurrence. Full article

Plant-Derived Extracellular Vesicles extracellular vesicles (PDEVs) from organic agriculture (without the use of pesticides and microbicides) contain high levels of antioxidants. Organic PDEVs have shown an increased antioxidant power compared to PDEVs from single plants, suggesting a synergistic effect of the bioactives constitutively expressed in the PDEVs from single fruits. With this study, we wanted to investigate the beneficial effects of a mix of PDEVs on human skin cells. We found detectable levels of citric acid, ascorbic acid, glutathione, catalase, and SOD in a mix of PDEVs deriving from five different fruits (grape, red orange, papaya, pomegranate, and tangerine). We then treated H₂O₂-conditioned fibroblasts with the mix of PDEVs. The results showed that the PDEVs’ mixture reverted the H₂O₂-induced redox imbalance, restoring mitochondrial homeostasis, with a strong reduction of mitochondrial anion superoxide and an increase in sirtuin levels. The antioxidant action was consistent with wound repair on a lesion produced in a fibroblast’s monolayer. This result was consistent with an increased level of vimentin and matrix metalloproteinase-9, whose expression is directly related to the efficiency of the reparative processes. These data support a beneficial role of PDEVs in both preventing and treating skin injuries through their potent antioxidant and reparative activities. Full article

Background/Objectives: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies. Results: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions. Conclusions: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required. Full article