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The World's First Acne Dysbiosis-like Model of Human 3D Ex Vivo Sebaceous Gland Colonized with and .Microorganisms Aug 2023Acne-prone skin is associated with dysbiosis involving () and () causing increased seborrhea in sebaceous glands (SG) and inflammation. Human primary sebocytes were...
Acne-prone skin is associated with dysbiosis involving () and () causing increased seborrhea in sebaceous glands (SG) and inflammation. Human primary sebocytes were cultivated using 1.10 UFC/mL Type IA (facial acne, ATCC6919) and/or 1.10 UFC/mL (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 1.10 UFC/mL Type 1A and/or 1.10 UFC/mL (wild-type facial skin strain) through prior fixation and immunostaining for MC5R, and nuclei (DAPI) via Z-stack confocal microscopy bioimaging (Leica SP5X & FIJI software, Version 2.9.0). 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 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 reduced contact time, sequential inoculation and rinsing step. Bioimaging revealed strong labeling in the active areas of the pilosebaceous unit. 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 inoculation.
PubMed: 37764027
DOI: 10.3390/microorganisms11092183 -
Children (Basel, Switzerland) Aug 2023This study aimed to investigate the levels of skin moisture and sebum in children with a house dust allergy without skin symptoms. This was a case-control study...
This study aimed to investigate the levels of skin moisture and sebum in children with a house dust allergy without skin symptoms. This was a case-control study involving children, aged 0-18 years, who were being followed up for an allergic airway disease in a pediatric allergy clinic. Age, gender, hemogram parameters, and IgE values were evaluated. The skin moisture and sebum percentages of the patients and control group were measured by a non-invasive bioimpedance method using a portable digital skin moisture and sebum measurement device on the cubital fossa. The median value of the skin moisture percentage in the house dust mite allergy-positive patient group was significantly lower than that in the house dust mite allergy-negative patients and the control group ( < 0.001). The house dust mite allergy-positive patient group had the lowest skin sebum content. However, there was no statistical significance among the groups in terms of skin sebum percentage ( = 0.102). In the study, children with a house dust allergy were found to have lower levels of skin moisture and sebum. The regular use of moisturizers for children with a house dust allergy should be kept in mind as an effective solution to protect the skin barrier and reduce skin symptoms.
PubMed: 37761444
DOI: 10.3390/children10091483 -
Cancers Sep 2023Squamous cell carcinoma (SCC) is one of the most common forms of skin cancer in humans, and Neural Wiskott-Aldrich Syndrome Protein (N-WASP) plays a crucial role in...
Squamous cell carcinoma (SCC) is one of the most common forms of skin cancer in humans, and Neural Wiskott-Aldrich Syndrome Protein (N-WASP) plays a crucial role in epidermal homeostasis. To elucidate the role of N-WASP in skin cancer, we generated mice which expressed constitutively active KRas (KRas) in keratinocytes with either homozygous (N-WASP) or heterozygous (N-WASP) N-WASP knockout upon Tamoxifen (TAM) injection. Both the N-WASP and N-WASP mice had similar body weights and no congenital malformations prior to the injection of TAM. Within 2 weeks of the injections, the N-WASP mice exhibited significant reductions in weight coupled with visible tumors at numerous sites, unlike the N-WASP mice, which had no visible tumors. We found that both sets of mice had oily, sticky skin and wet eyes 3 weeks after their exposure to TAM, indicating the overproduction of sebum/meibum. At 37 days post TAM injection, several notable observations were made. Tumors collected from the N-WASP mice had small- to large-sized keratin pearls that were not observed in the N-WASP mice. A Western blot and immunostaining analysis both highlighted significantly higher levels of expression of SCC markers, such as the cytokeratins 8, 17, 18, and 19 and TP63, in the tumors of the N-WASP mice compared to those of the latter group. Furthermore, we noted increases in the expression levels of EGFR, P-ERK, GLUT1, P-mTOR, and P-4EBP in the N-WASP mice, suggesting that the deletion of N-WASP in the keratinocytes enhanced KRas signaling and glucose uptake, resulting in aggressive tumor formation. Interestingly, a thickening of the epidermal layer within the esophagus and tongue was only observed in the N-WASP mice. Immunostaining for PCNA emphasized a significantly higher number of PCNA-positive cells in the skin of the N-WASP mice compared to their counterparts, implying that epidermal thickening and enhanced tumorigenesis are due to an increased proliferation of keratinocytes. Through our results, we have established that N-WASP plays a tumor-suppressive role in skin cancer.
PubMed: 37760426
DOI: 10.3390/cancers15184455 -
Skin Research and Technology : Official... Sep 2023Evidence suggests that sebum content is important in skin disorders such as acne. However, sebum levels change depending on the external environment, and quantifying...
BACKGROUND
Evidence suggests that sebum content is important in skin disorders such as acne. However, sebum levels change depending on the external environment, and quantifying skin sebum levels is challenging. Here, we propose an optimal method for quantifying the facial sebum level.
MATERIALS AND METHODS
Four hundred and sixty participants (160 males and 300 females) aged 20-40 were enrolled in this study. A Sebumeter SM 810 was used to measure the sebum level at five facial locations: the forehead, the chin, the left cheek, the right cheek, and the nose. The participants were divided into two groups; one group underwent a one-time measurement (n = 390, male: female = 120: 270), and the other underwent three consecutive measurements (n = 70, male: female = 40: 30). The casual sebum level (CSL) was measured in all patients after a 30-min acclimatization; subsequently, the sebum removal process was conducted, followed by a resting period of 1 h to determine the sebum excretion rate (SER). Spearman's correlation analysis and the Wilcoxon signed-rank test were used to compare the sebum level consistency and differences between the groups.
RESULTS
Although three consecutive measurements better reflected the sebum content, the one-time measurement also represented the relative sebum level. One hour after sebum removal, the sebum level recovered to 70%-90%; thus, this method was applicable for use in SER quantification. Of the five testing points, the sebum content was highest in the nose and lowest in the cheeks (both left and right). In addition, the cheeks were the most stable sites in terms of testing points, testing times, and CSL/SER values. A one-time measurement of the CSL could represent the SER 1 h after the sebum removal. In our cohort, the sebum level of males with oily skin was decreased at age 32-35, and that of males with non-oily skin increased at 28-35. The opposite trend was observed in female participants.
CONCLUSION
Sebum measurement methods were assessed, including testing times, indices (interval of time) and sites in a conditioned external environment. A one-time measurement of the CSL 1 h after sebum removal was sufficient to determine the sebum level and SER, and the cheeks are recommended as the testing site. Sex and skin type differences were observed in sebum level changes with age.
Topics: Humans; Female; Male; Adult; Sebum; Face; Cheek; Nose; Forehead
PubMed: 37753695
DOI: 10.1111/srt.13454 -
Scientific Reports Sep 2023Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the...
Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the development of acne vulgaris, while other phylotypes have been linked to healthy skin. In this scenario, bacterial extracellular vesicles (EVs) play a role in the interkingdom communication role with the human host. The purpose of this study was to examine the impact of EVs generated by various phylotypes of C. acnes on inflammation and sebum production using different in vitro skin cell types. The main findings of this study reveal that the proteomic profile of the cargo embodied in the EVs reflects distinct characteristics of the different C. acnes phylotypes in terms of life cycle, survival, and virulence. The in vitro skin cell types showed an extended pro-inflammatory modulation of SLST A1 EVs consistently triggering the activation of the inflammation-related factors IL-8, IL-6, TNFα and GM-CSF, in comparison to SLST H1 and SLST H2. Additionally, an acne-prone skin model utilizing PCi-SEB and arachidonic acid as a sebum inducer, was employed to investigate the impact of C. acnes EVs on sebum regulation. Our findings indicated that all three types of EVs significantly inhibited sebum production after a 24-h treatment period, with SLST H1 EVs exhibiting the most pronounced inhibitory effect when compared to the positive control. The results of this study highlight the protective nature of C. acnes SLST H1 EVs and their potential use as a natural treatment option for alleviating symptoms associated with inflammation and oily skin.
Topics: Humans; Proteomics; Skin; Skin Diseases; Extracellular Vesicles; Acne Vulgaris; Propionibacterium acnes; Factor VIII; Inflammation
PubMed: 37749255
DOI: 10.1038/s41598-023-43354-w -
Scientific Reports Sep 2023Testosterone is thought to be incorporated in growing hair strands so that specific hair segments reflect average free hormone concentrations from the corresponding time...
Testosterone is thought to be incorporated in growing hair strands so that specific hair segments reflect average free hormone concentrations from the corresponding time period. However, the exact mechanisms of hormone integration in scalp hair have not yet been established and it is not known how testosterone is stored in the hair segments over time. The aim of this study was to investigate the stability of testosterone concentrations in hair as it grows and to determine if segmental hair analysis can be used as a retrospective testosterone diary. Thirty men and 40 women provided two hair samples and 16 saliva samples during a period of three months. Hair growth between the two samplings was measured. Hair samples were cut into 10 mm segments resulting in three segments from the first sampling and six segments from the second sampling. Hair samples were pulverised and extracted with methanol. Hair testosterone concentrations were analysed using an in-house radioimmunoassay. Salivary testosterone was analysed using a commercial enzyme-linked immunosorbent assay (Demeditec). The results demonstrated that there is a degree of segmental hormone conservation over time (rho = 0.405-0.461, p < 0.001, n = 66-67), but also highlighted three potential confounders. Firstly, testosterone concentrations were higher in distal hair segments (mean concentration ratio most distal by most scalp-near was 1.55, SD 0.70), which may be due to continuous hormone integration from sebum and changes in hair matrix composition. Secondly, more frequent hair washing stunted the increase in testosterone concentrations in distal segments (rho = -0.404, p = < 0.001, n = 66). And lastly, intra- and inter- individual variability in hair growth rate influenced the temporal resolution along the hair, although mean growth rate was indeed 30.0 mm for three months. In a multiple regression model the biological sex, natural hair colour, and relationship status were significant explanatory variables to hair testosterone concentrations. The current results indicate that repeated hair sampling near the hair roots during a study may be preferable to analysing concentration changes between proximal and distal segments within the same hair sample. Also, hair testosterone analysis needs to be adjusted for sex and the natural hair colour.
Topics: Male; Female; Humans; Testosterone; Hair Analysis; Retrospective Studies; Hair; Hair Follicle
PubMed: 37749110
DOI: 10.1038/s41598-023-41672-7 -
International Wound Journal Jan 2024Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges....
Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.
Topics: Humans; Cicatrix, Hypertrophic; Keloid; Keratinocytes; Fibroblasts; Myofibroblasts
PubMed: 37697692
DOI: 10.1111/iwj.14384 -
Cureus Aug 2023Background Prolonged acne inflammation causes scar formation, one of which is post-acne keloids. Sebum, total cholesterol, and low-density lipoprotein (LDL) level can...
Background Prolonged acne inflammation causes scar formation, one of which is post-acne keloids. Sebum, total cholesterol, and low-density lipoprotein (LDL) level can influence post-acne keloids. This study aims to determine the association between sebum, total cholesterol, and LDL levels with post-acne keloids to better define the predisposing factors for this condition. Methods This study used primary data involving sociodemographics, clinical features, keloid classification, sebum levels, total cholesterol levels, and LDL levels in post-acne keloid patients at the Dermatology, Venereology, and Aesthetics Outpatient Clinics of Dr. Mohammad Hoesin General Hospital Palembang, Indonesia. Study samples were patients who fulfilled the inclusion and exclusion criteria by consecutive sampling. The data then underwent univariate and bivariate analyses to show the association between variables. Result A total of 22 patients with post-acne keloids participated. The subjects presented mostly with major keloids based on the classification (59.1%). The patients were predominantly 21-30 years old (50%) and male (90.9%). The keloids had onsets >six months to one year (45.5%), durations of one to five years (77.3%), and multiple presentations (68.2%). Vancouver Scar Scale (VSS) assessment showed mainly red vascularity (40.9%), mixed pigmentation (68.2%), >5 mm keloid height (59.1%), and firm pliability (40.9%). Most patients presented with pruritus (86.4%) but without pain (54.5%). Most had low levels of sebum (50%), normal total cholesterol (90.9%), and near-optimal LDL level (40.9%). There were no significant association between sebum (p = 1.000), total cholesterol (p = 1.000), and LDL (p = 0.376) levels with post-acne keloids. However, LDL levels above normal were most found in this study (68.2%). Conclusions There is no association between sebum, total cholesterol, and LDL levels with post-acne keloids. Despite the fact that LDL level was not statistically significant, there has been a rise in LDL level in the research subjects. Further research with a larger number of subjects and consideration of multicenter study through retrospective/prospective methods and complete lipid profile examinations is still required to provide a more representative study.
PubMed: 37692568
DOI: 10.7759/cureus.43096 -
Environmental Research Dec 2023PFAS are known contaminants of indoor dust. Despite the adherence of such dust to skin, the dermal penetration potential of PFAS is not well understood. By applying in...
PFAS are known contaminants of indoor dust. Despite the adherence of such dust to skin, the dermal penetration potential of PFAS is not well understood. By applying in vitro physiologically based extraction tests, the bioaccessibility of 17 PFAS from indoor dust to synthetic human sweat sebum mixtures (SSSM) was assessed. The composition of the SSSM substantially impacted the bioaccessibility of all target compounds. PFAS bioaccessibility in a 1:1 sweat:sebum mixture ranged from 54 to 92% for perfluorocarboxylic acids (PFCAs) and 61-77% for perfluorosulfonic acids (PFSAs). Commonly applied cosmetics (foundation, sunscreen, moisturiser, and deodorant) significantly impacted the dermal bioaccessibility of target PFAS, e.g., the presence of moisturiser significantly decreased the total bioaccessibility of both PFCAs and PFSAs. Preliminary human exposure estimates revealed dermal contact with indoor dust could contribute as much as pathways such as drinking water and dust ingestion to an adult's daily intake of PFAS. While further research is needed to assess the percutaneous penetration of PFAS in humans, the current study highlights the potential substantial contribution of dermal exposure to human body burdens of PFAS and the need for further consideration of this pathway in PFAS risk assessment studies.
Topics: Adult; Humans; Dust; Environmental Exposure; Air Pollution, Indoor; Skin; Cosmetics; Fluorocarbon Polymers; Fluorocarbons
PubMed: 37683793
DOI: 10.1016/j.envres.2023.117093