Search Results (35)

Reticulated acanthoma with sebaceous differentiation (RASD) is a rare, benign cutaneous neoplasm. Its variable clinical presentation frequently mimics both benign and malignant entities, posing a significant diagnostic challenge. We report a case of pigmented RASD in a 78-year-old Malay male of Fitzpatrick skin type IV who presented with a 5-year history of an 8 × 5 mm deeply pigmented, asymmetrical nodule on the left upper back, with a 2 mm central raised area showing less pigmentation. The lesion was clinically suspicious for malignant melanoma. Histopathological examination revealed characteristic features of RASD: a broad, plate-like, reticulated and pigmented epidermal proliferation with clusters of mature sebocytes at the bases of anastomosing rete ridges. Following biopsy confirmation, the residual lesion is being managed conservatively with observation. This case demonstrates an unusual heavily pigmented clinical presentation that completely obscured the typical yellowish hue associated with sebaceous differentiation, highlighting pigmented RASD as an important diagnostic pitfall in patients with skin of color. In conclusion, RASD should be included in the differential diagnosis of pigmented cutaneous lesions, especially in patients with skin of color. Recognition of this benign entity can prevent unnecessary aggressive surgical intervention. Full article

Chronic dermatological conditions such as acne vulgaris, androgenetic alopecia (AGA), and alopecia areata (AA) affect hundreds of millions worldwide and contribute substantially to quality-of-life impairment. Despite the availability of systemic retinoids, anti-androgens, and JAK inhibitors, therapeutic responses remain heterogeneous and relapse is common, underscoring the need for biologically grounded stratification. Over the past decade, large genome-wide association studies and functional analyses have clarified disease-specific and cross-cutting mechanisms. In AA, multiple independent HLA class II signals and immune-regulatory loci such as BCL2L11 and LRRC32 establish antigen presentation and interferon-γ/JAK–STAT signalling as central drivers, consistent with clinical responses to JAK inhibition. AGA is driven by variation at the androgen receptor and 5-α-reductase genes alongside WNT/TGF-β regulators (WNT10A, LGR4, RSPO2, DKK2), explaining follicular miniaturisation and enabling polygenic risk prediction. Acne genetics highlight an immune–morphogenesis–lipid triad, with loci in TGFB2, WNT10A, LGR6, FASN, and FADS2 linking follicle repair, innate sensing, and sebocyte lipid metabolism. Barrier modulators such as FLG and OVOL1, first described in atopic dermatitis, further shape inflammatory thresholds across acne and related phenotypes. Together, these findings position genetics not as an abstract catalogue of risk alleles but as a map of tractable biological pathways. They provide the substrate for patient-stratified interventions ranging from JAK inhibitors in AA, to endocrine versus morphogenesis-targeted strategies in AGA, to lipid- and barrier-directed therapies in acne, while also informing cosmetic practices focused on barrier repair, sebaceous balance, and follicle health. Full article

A fast-paced lifestyle contributes to heightened emotional stress, driving the demand for milder and safer cosmetic ingredients that can counteract stress-induced skin damage—a focus of cutting-edge research in the field. Aim: The aim was to elucidate the role and mechanistic basis of tea (Camellia sinensis) seed meal saponin (Sap) in regulating stress-induced sebum overproduction and inflammatory responses. Methods: The composition and chemical structure of Sap were analyzed using UV-vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In vitro models of cortisone-induced excessive lipid accumulation and the tumor necrosis factor-alpha (TNF-α)-stimulated inflammatory models were established on sebaceous gland cells (SZ95) and normal human epidermal keratinocytes (NHEKs), respectively. Cortisol and inflammatory cytokine secretion levels in cells were detected using ELISA. Additionally, the signaling pathways were revealed by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-PCR). Results: Five saponins were identified in the Sap extract, all belonging to the oleanolic-acid-type pentacyclic triterpenes. Sap treatment significantly attenuated cortisone-induced cortisol secretion and lipid accumulation in SZ95 sebocytes. Mechanistically, Sap inhibited the 11β-HSD1/SREBP-1 pathway, which mediates its sebosuppressive effects, while concurrently down-regulating the mRNA expression of key downstream transcription factors and enzymes, including SREBP-1, FAS, and ACC. Additionally, Sap treatment significantly attenuated TNF-α-stimulated cortisol secretion and inflammatory cytokine (IL-1β, IL-6, and IL-8) production in NHEK cells through the inhibition of the 11β-HSD1/TLR2/NF-κB signaling pathway. Conclusion: Sap demonstrated dual inhibitory effects, suppressing both emotional-stress-induced sebum overproduction and inflammatory cytokines secretion. Full article

Background: Hormonal fluctuations significantly influence skin physiology, affecting collagen production, sebum regulation, pigmentation, and tissue repair. Hormonal therapies are increasingly used in cosmetic dermatology to address age-related and hormone-dependent skin changes. Methods: This narrative review synthesizes the current literature on the mechanisms, clinical applications, and future directions of hormonal therapies in dermatologic aesthetics. Studies were selected through a comprehensive search on PubMed, Scopus, and Web of Science. Results: Estrogens, androgens, progesterone, and other hormones act on skin through specific receptors, modulating fibroblast, sebocyte, and melanocyte activity. Clinical applications include hormone-based strategies for anti-aging, acne, melasma, alopecia, and postmenopausal atrophy. Both systemic (e.g., HRT) and topical (e.g., clascoterone, phytoestrogens) approaches are discussed. Safety concerns, including systemic absorption and off-label use, require careful evaluation. Emerging technologies such as SERMs, nanocarriers, and regenerative combinations suggest promising future avenues. Conclusions: Hormonal therapies offer a biologically rational and increasingly evidence-based tool in cosmetic dermatology. Responsible integration into clinical practice depends on personalized approaches, ethical prescribing, and further research on long-term safety and efficacy. Full article

Sebum secreted by sebaceous glands mixes with sweat to form a protective film that aids in maintaining skin health. Reduced sebum production compromises such barrier functions, potentially leading to severe itchiness and inflammation. Therefore, incorporating moisturizers with ingredients promoting sebum secretion is desirable. Wild watermelon possesses moisturizing and antioxidant properties, and its extracts are utilized in skin cosmetics and supplements. This study investigates whether seed watermelon (Citrullus mucosospermus (Fursa))—a species closely related to wild watermelon—influences sebum synthesis and can serve as a skin cosmetic raw ingredient. Several bioactive compounds—including coniferyl alcohol, coniferin, and p-coumaryl alcohol—were identified in the active third fraction of the fruit extract. Subsequently, SZ95 sebocytes stimulated with linoleic acid were stained using Oil Red O to detect lipogenesis facilitated by the identified bioactive compounds. Coniferyl alcohol promoted linoleic acid-stimulated lipogenesis by approximately 2.2-fold at a concentration of 300 µM. Lipidomic analyses confirmed an increase in total lipid content following coniferyl alcohol treatment, with notable increases in cholesterol ester, cardiolipin, and simple lipid content. Overall, these findings suggest that seed watermelon contains compounds that do influence sebum synthesis. Consequently, skin cosmetics containing seed watermelon fruit extracts with linoleic acid may benefit individuals with dry skin. Full article

Galectin-12, a member of the galectin family of glycan-binding proteins, exhibits restricted tissue distribution, primarily in adipocytes and sebocytes. In sebocytes, it modulates the cell cycle, influences lipid metabolism through interactions with peroxisome proliferator-activated receptor γ (PPARγ), and exerts immunomodulatory functions by activating immune signaling pathways. Dysregulation of sebocyte homeostasis, lipid metabolism, and immune responses contributes to the pathogenesis of a number of skin diseases, underscoring the therapeutic potential of targeting galectin-12. The review summarizes and discusses current developments in the field to foster future research in this important but underexplored galectin. Full article

The sebaceous gland (SG) is an integral part of the pilosebaceous unit and is a very active and dynamic organ that contributes significantly to the maintenance of skin homeostasis. In addition to its primary role in sebum production, the SG is involved in the maintenance of skin barrier function, local endocrine/neuroendocrine function, the innate immune response, and the regulation of skin bacterial colonization. Structural and functional alterations of SGs leading to the dysregulation of sebum production/composition and immune response may contribute to the pathogenesis of inflammatory dermatoses. This review summarises the current knowledge on the contribution of SGs to the pathogenesis of common inflammatory skin diseases. These findings are crucial for the development of more effective therapeutic strategies for the treatment of inflammatory dermatoses. Full article

Given the importance of peroxisome proliferator-activated receptor (PPAR)-gamma in epidermal inflammation and carcinogenesis, we analyzed the transcriptomic changes observed in epidermal PPARγ-deficient mice (Pparg-/-^epi). A gene set enrichment analysis revealed a close association with epithelial malignancy, inflammatory cell chemotaxis, and cell survival. Single-cell sequencing of Pparg-/-^epi mice verified changes to the stromal compartment, including increased inflammatory cell infiltrates, particularly neutrophils, and an increase in fibroblasts expressing myofibroblast marker genes. A comparison of transcriptomic data from Pparg-/-^epi and publicly available human and/or mouse actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) revealed a strong correlation between the datasets. Importantly, PPAR signaling was the top common inhibited canonical pathway in AKs and SCCs. Both AKs and SCCs also had significantly reduced PPARG expression and PPARγ activity z-scores. Smaller reductions in PPARA expression and PPARα activity and increased PPARD expression but reduced PPARδ activation were also observed. Reduced PPAR activity was also associated with reduced PPARα/RXRα activity, while LPS/IL1-mediated inhibition of RXR activity was significantly activated in the tumor datasets. Notably, these changes were not observed in normal sun-exposed skin relative to non-exposed skin. Finally, Ppara and Pparg were heavily expressed in sebocytes, while Ppard was highly expressed in myofibroblasts, suggesting that PPARδ has a role in myofibroblast differentiation. In conclusion, these data provide strong evidence that PPARγ and possibly PPARα represent key tumor suppressors by acting as master inhibitors of the inflammatory changes found in AKs and SCCs. Full article

Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects. Full article

Sebaceous gland tumors are neoplasms originating from the sebaceous gland and are the third most common type of skin tumor, accounting for 21–35% of all cutaneous neoplasms in dogs. According to their histopathological characteristics, sebaceous gland tumors can be classified into adenoma as a benign tumor and epithelioma as a malignant tumor. Sebaceous epithelioma is distinguished from sebaceous adenoma by containing 90% or more reserve cells. However, this simple numerical criterion is insufficient to histologically distinguish between epitheliomas and adenomas. In addition, sebaceoma in humans, a similar tumor to sebaceous epithelioma, is a term used for tumors with more than 50% of reserve cells, unlike epithelioma. Therefore, we aimed to compare and characterize the histological and immunohistochemical profiles of comprehensive sebaceous adenoma, epithelioma, and borderline tumors that have more than 50% but less than 90% of reserve cells. A total of 14 canine sebaceous tumors were diagnosed as seven adenomas, four borderline tumors, and three epitheliomas. Histologically, the sebaceous adenomas showed nodules consisting of mature sebocytes surrounded by monolayer basaloid cells. In contrast, the portion of the reserve cells was increased, the portion of lipidized cells was decreased, and the majority of lipidized cells were found to be immature in sebaceous epithelioma. In the sebaceous adenomas, necrosis was not observed and mitotic figures were rarely seen. However, necrosis and mitotic figures were highly frequent in both borderline tumor and sebaceous epithelioma. Immunohistochemistry revealed that borderline tumor and sebaceous epithelioma showed significantly higher expression against Ki-67 than sebaceous adenoma. We conclude that it is more accurate to employ the cut-off value of 50% reserve cells in humans rather than the current 90% reserve cells for classifying sebaceous gland tumors in dogs, thereby providing new insight into the characterization of the sebaceous gland tumors. Full article

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect—the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris. Full article

This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin’s mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch which enhances the transactivation of lipogenic and proinflammatory transcription factors, including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ) and signal transducer and activator of transcription 3 (STAT3), but reduces the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin’s desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin. Full article

Acne-prone skin is associated with dysbiosis involving Cutibacterium acnes (C. acnes) and Staphylococcus epidermidis (S. epidermidis) causing increased seborrhea in sebaceous glands (SG) and inflammation. Human primary sebocytes were cultivated using 1.10⁶ UFC/mL C. acnes Type IA (facial acne, ATCC6919) and/or 1.10⁵ UFC/mL S. epidermidis (unknown origin, ATCC12228) for 48 h in our SEB4GLN-optimized media without antibiotics. Bacteria and sebocytes were enumerated and assessed to determine their viability. Lipid production was imaged and quantified via Nile Red staining. SG with hair follicles were microdissected from healthy skin and cultured using 1.10⁵ UFC/mL C. acnes Type 1A and/or 1.10⁴ UFC/mL S. epidermidis (wild-type facial skin strain) through prior fixation and immunostaining for MC5R, C. acnes and nuclei (DAPI) via Z-stack confocal microscopy bioimaging (Leica SP5X & FIJI software, Version 2.9.0). C. acnes growth was not impacted when co-cultivated with sebocytes (2D) or SG (3D) models. Phylotype IA stimulated sebocyte lipid production, which had no impact on viability. The S. epidermidis reference strain overproliferated, inducing sebocyte mortality. For 3D SG model, culture conditions were optimized using a wild-type facial skin strain at a lower concentration, 1:10 ratio to C. acnes, reduced contact time, sequential inoculation and rinsing step. Bioimaging revealed strong C. acnes labeling in the active areas of the pilosebaceous unit. S. epidermidis formed biofilm, which was distributed across the SG via non-specific fluorescence imaging. We developed an innovative model of a sebaceous gland that mimics acne-prone skin with lipid overproduction and virulent phylotype IA C. acnes inoculation. Full article

A new skincare application scenario for dark tea, a unique and post-fermented tea popular in the health food industry, was developed in this paper. The effects of dark tea polysaccharide (DTP) on stress-induced skin problems and its mechanism of action were investigated by modeling cortisone-induced stress injury in human HaCaT keratinocytes and SZ95 sebaceous gland cells. The results showed a reduced cortisol conversion induced by cortisone under the action of DTP with a concentration of 200 μg/mL, probably by inhibiting the expression of the HSD11B1 enzyme. DTP was also able to suppress the cortisone-induced elevation of lipid levels in SZ95 sebocytes at this concentration. In addition, the composition and structure of DTP were verified by ultrafiltration, ultraviolet-visible spectrophotometry (UV-VIS), high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) and infrared spectroscopy. In brief, DTP has a unique and significant stress-relieving effect, which provides new ideas for the development of new ingredients for the skin care industry. Full article

Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options. Full article