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Canine apolipoprotein A‐I (ApoA‐I) amyloidosis has only been reported as an age‐related pulmonary vascular condition. In this report, the authors identified cutaneous ApoA‐I amyloidosis within a fibroadnexal hamartoma in a dog. Based on proteomic analysis using mass spectrometry, the mechanism of ApoA‐I amyloidogenesis is discussed. [ABSTRACT FROM AUTHOR]

Background: Sebum physiology and its contributions to acne vulgaris (AV) pathophysiology have been long debated. Within the pilosebaceous unit, androgens drive sebocyte production of sebum, comprising mono-, di-, and triglycerides (the latter converted to fatty acids); squalene; cholesterol; cholesterol esters; and wax esters. Upon release to the skin surface, human sebum has important roles in epidermal water retention, antimicrobial defenses, and innate immune responses. Aims: Alterations in sebum alone and with other pathogenic factors (inflammation, follicular hyperkeratinization, and Cutibacterium acnes [C. acnes] proliferation) contribute to AV pathophysiology. Androgen-driven sebum production, mandatory for AV development, propagates C. acnes proliferation and upregulates inflammatory and comedogenic cascades. Results: Some sebum lipids have comedogenic effects in isolation, and sebum content alterations (including elevations in specific fatty acids) contribute to AV pathogenesis. Regional differences in facial sebum production, coupled with patient characteristics (including sex and age), help exemplify this link between sebum alterations and AV lesion formation. Conclusions: To date, only combined oral contraceptives and oral spironolactone (both limited to female patients), oral isotretinoin and topical clascoterone (cortexolone 17α-propionate) modulate sebum production in patients with AV. A better understanding of mechanisms underlying sebaceous gland changes driving AV development is needed to expand the AV treatment armamentarium. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris poses a significant dermatological challenge, necessitating alternative treatments due to limitations and side effects associated with current therapies. This pilot clinical trial investigated the feasibility and efficacy of precision cryotherapy for acne vulgaris. Methods: A total of 20 volunteers underwent targeted precision cryotherapy using a carbon dioxide‐based device. Treatment outcomes were assessed using various parameters, including Investigator Global Assessment (IGA) score, acne lesion count, erythema index (EI), global evaluation score, and participant satisfaction. Safety monitoring included adverse event reporting and physical examination. Results: Precision cryotherapy demonstrated a significant reduction (90.25%) in the acne lesion count by week 4, with clinical improvement indicated by IGA score reduction (p < 0.001). The EI showed notable improvements at weeks 1, 2, and 4. The global evaluation score demonstrated a 75%–100% clinical improvement at Visit 4. Participants reported high satisfaction (6.75 ± 0.79) with the procedure. No adverse event or discomfort was reported. Conclusion: Precision cryotherapy effectively improved acne lesions, which was safe and satisfactory for participants. These findings suggest its potential as an alternative therapeutic modality, especially for populations with limited treatment options. Further research is needed to validate the results and explore underlying mechanisms. [ABSTRACT FROM AUTHOR]

Cattle mange causes extreme itchiness, and the associated stress is an animal welfare concern that leads to economic losses due to decreased cattle productivity and deworming costs. This study investigated the reason why Chorioptic mites, C. bovis and C. texanus, preferentially infest the tail root region (rTR) and performed histological and biochemical analysis focusing on the volatile components of host odors that serve as the starting point for infestation of parasitic arthropods. Skin samples were taken from the rTR, lateral abdominal, and central masseteric, with the latter two designated as comparison sites. The two and three-dimensional histological analysis measured each sebaceous and sweat gland percentage per unit volume. The q-PCR analyzed the expression levels of ALDH1A1 and LOC785756, which are genes associated with volatile odoriferous compounds that serve as repellency and attractive messengers for ticks. Immunohistochemistry stained three sites with anti-androgen binding protein beta-like (ABPβ-like), encoded by LOC785756, antibody. The three-dimensional analysis showed that sebaceous glands in the rTR tend to be more continuous and existed in larger masses than in other regions. The expression level of LOC785756 was significantly higher in the rTR, and immunohistochemistry revealed the presence of ABPβ-like in the sebaceous gland with strong positive signals in the rTR. These results suggest that C. bovis/ texanus selectively infests the rTR because that skin has well-developed sebaceous glands, including a large amount of ABPβ-like, which acts as a mite attractant. [ABSTRACT FROM AUTHOR]

[Display omitted] The cytokine TSLP promotes type 2 immune responses and can induce adipose loss by stimulating lipid loss from the skin through sebum secretion by sebaceous glands, which enhances the skin barrier. However, the mechanism by which TSLP upregulates sebaceous gland function is unknown. This study investigated the mechanism by which TSLP stimulates sebum secretion and adipose loss. RNA-sequencing analysis was performed on sebaceous glands isolated by laser capture microdissection and single-cell RNA-sequencing analysis was performed on sorted skin T cells. Sebocyte function was analyzed by histological analysis and sebum secretion in vivo and by measuring lipogenesis and proliferation in vitro. This study found that TSLP sequentially stimulated the expression of lipogenesis genes followed by cell death genes in sebaceous glands to induce holocrine secretion of sebum. TSLP did not affect sebaceous gland activity directly. Rather, single-cell RNA-sequencing revealed that TSLP recruited distinct T-cell clusters that produce IL-4 and IL-13, which were necessary for TSLP-induced adipose loss and sebum secretion. Moreover, IL-13 was sufficient to cause sebum secretion and adipose loss in vivo and to induce lipogenesis and proliferation of a human sebocyte cell line in vitro. This study proposes that TSLP stimulates T cells to deliver IL-4 and IL-13 to sebaceous glands, which enhances sebaceous gland function, turnover, and subsequent adipose loss. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Sebaceous gland tumors are less studied than other tumors because they have a relatively good prognosis and low incidence compared to other tumors. In particular, sebaceous gland tumors have received little attention in veterinary medicine, leading to diagnostic uncertainty. However, unlike sebaceous adenoma, epithelioma can metastasize and has a high mortality rate thus accurate diagnosis is essential. The present study aimed to validate and discuss the diagnostic criteria for sebaceous adenoma and epithelioma in dogs. 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. [ABSTRACT FROM AUTHOR]

Summary: Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir‐Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow‐up care is recommended for these potentially aggressive carcinomas. [ABSTRACT FROM AUTHOR]

Acne (syn. acne vulgaris) is a common inflammatory skin disorder associated with puberty and adolescence. The disease is characterized by comedoneous lesions, papules, pustules, and nodules that are mostly found on the face. These lesions are caused by intricate interactions between the pilosebaceous unit and the Cutibacterium acnes (C. acnes) bacteria. Unhealthy acne and its aftereffects, like pigment changes and scarring, have a detrimental impact on one’s quality of life. Recent years have seen a sharp increase in the approval of nucleic acid therapies (NATs), such as antisense oligonucleotides and short-interfering RNA medications, for rare diseases for which there are few or no effective treatments. These developments suggest that NATs may be useful in acne treatment plans down the road, as do clinical trials for microRNA (miRNA) modulation in skin contexts. We highlight promising miRNA targets for anti-acne therapy in this review. We outline the pathophysiology of acne in brief and emphasize the functions of C. acnes. Next, we concentrate on the distinct impacts of biofilm and planktonic C. acnes on a Toll-like receptor 2 axis that spans miR-146a-5p, which was recently discovered. Before discussing the potential contributions of miR-21- 5p, miR-233-3p, and miR-150-5p to inflammatory axes in acne, we evaluate miR-146a-5p in sebocytes. Finally, we address patient involvement in miRNA-related acne research and translational perspectives. [ABSTRACT FROM AUTHOR]

Sebaceous carcinoma (SC) is a slow-growing but aggressive malignant skin tumour derived from sebaceous glands. SC most commonly occurs in the periocular region, whereas extraocular sites are rare. SC of the nasal dorsum is a rare pathology, and only a few cases are reported worldwide. Here, we report a case of an 80-year-old man who presented with a mass over the nasal dorsum, diagnosed morphologically and immunohistochemically as sebaceous carcinoma. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown. Objectives: To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT. Methods: Human primary sebocytes were transfected with the human tert gene (h‑tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT. Results: The h‑tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT. Conclusions: We have developed an h‑tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases.

Abstract Background Single-cell RNA sequencing (scRNA-seq) has been widely applied to dissect cellular heterogeneity in normal and diseased skin. Sebaceous glands, essential skin components with established functions in maintaining skin integrity and emerging roles in systemic energy metabolism, have been largely neglected in scRNA-seq studies. Methods Departing from mouse and human skin scRNA-seq datasets, we identified gene sets expressed especially in sebaceous glands with the open-source R-package oposSOM. Results The identified gene sets included sebaceous gland-typical genes as Scd3, Mgst1, Cidea, Awat2 and KRT7. Surprisingly, however, there was not a single overlap among the 100 highest, exclusively in sebaceous glands expressed transcripts in mouse and human samples. Notably, both species share a common core of only 25 transcripts, including mitochondrial and peroxisomal genes involved in fatty acid, amino acid, and glucose processing, thus highlighting the intense metabolic rate of this gland. Conclusions This study highlights intrinsic differences in sebaceous lipid synthesis between mice and humans, and indicates an important role for peroxisomal processes in this context. Our data also provides attractive starting points for experimentally addressing novel candidates regulating sebaceous gland homeostasis.

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG‐rich (SGR) and SG‐poor (SGP) areas in AD. Both sebum and SC were sampled from SGR areas, while SC was sampled also from SGP areas in 54 adult patients with AD, consisting of 34 and 20 subjects, respectively with and without clinical involvement of face, and in 44 age and sex‐matched controls. Skin biophysics were assessed in all sampling sites. Disruption of the SBP was found to be associated with dysregulated lipidome. Abundance of sapienate and lignocerate, representing, respectively, sebum and the SC type lipids, were decreased in sebum and SC from both SGR and SGP areas. Analogously, squalene was significantly diminished in AD, regardless the site. Extent of lipid derangement in SGR areas was correlated with the AD severity. The abundance of aminoacids in the SC from SGR areas was altered more than that determined in SGP areas. Several gender‐related differences were found in both controls and AD subgroups. In conclusion, the SG activity was differently compromised in adult females and males with AD, in both SGR and SGP areas. In AD, alterations in the aminoacidome profiles were apparent in the SGR areas. Lipid signatures in association with aminoacidome and skin physical properties may serve the definition of phenotype clusters that associate with AD severity and gender. [ABSTRACT FROM AUTHOR]

Background: Single-cell RNA sequencing (scRNA-seq) has been widely applied to dissect cellular heterogeneity in normal and diseased skin. Sebaceous glands, essential skin components with established functions in maintaining skin integrity and emerging roles in systemic energy metabolism, have been largely neglected in scRNA-seq studies. Methods: Departing from mouse and human skin scRNA-seq datasets, we identified gene sets expressed especially in sebaceous glands with the open-source R-package oposSOM. Results: The identified gene sets included sebaceous gland-typical genes as Scd3, Mgst1, Cidea, Awat2 and KRT7. Surprisingly, however, there was not a single overlap among the 100 highest, exclusively in sebaceous glands expressed transcripts in mouse and human samples. Notably, both species share a common core of only 25 transcripts, including mitochondrial and peroxisomal genes involved in fatty acid, amino acid, and glucose processing, thus highlighting the intense metabolic rate of this gland. Conclusions: This study highlights intrinsic differences in sebaceous lipid synthesis between mice and humans, and indicates an important role for peroxisomal processes in this context. Our data also provides attractive starting points for experimentally addressing novel candidates regulating sebaceous gland homeostasis. [ABSTRACT FROM AUTHOR]

Insulin affects metabolic processes in different organs, including the skin. The sebaceous gland (SG) is an important appendage in the skin, which responds to insulin-mediated signals, either directly or through the insulin growth factor 1 (IGF-1) axis. Insulin cues are differently translated into the activation of metabolic processes depending on several factors, including glucose levels, receptor sensitivity, and sebocyte differentiation. The effects of diet on both the physiological function and pathological conditions of the SG have been linked to pathways activated by insulin and IGF-1. Experimental evidence and theoretical speculations support the association of insulin resistance with acne vulgaris, which is a major disorder of the SG. In this review, we examined the effects of insulin on the SG function and their implications in the pathogenesis of acne. [ABSTRACT FROM AUTHOR]

Sebaceoma is a rare benign tumor arising from the sebaceous gland of the skin. Sebaceoma often occurs on the head and neck but rarely on the ears. We present the case of a 78-year-old female patient with a two-year history of a protruding mass in her left ear. Physical examination revealed a well-circumscribed plaque in the crus of the helix of the left ear. A wide local excisional biopsy was taken, and the mass was subjected to histopathologic assessment. While the mass showed cytological findings indicating sebaceoma, it also presented malignant features architecturally and immunohistochemically. Based on these findings, the tumor was regarded as a sebaceoma of borderline malignancy. [ABSTRACT FROM AUTHOR]

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Acne is one of the most common dermatoses. It is a chronic inflammatory disease of pilosebaceous units. The pathogenesis of the disease consists of: hyperproliferation of hair follicle opening cells and the formation of microcomedones closing its opening. Excessive activity of the sebaceous glands and increased sebum production. Inflammatory reaction induced by Cutibacterium acnes. Acne most often occurs between the ages of 11 and 30. Acne changes affect adults more and more often. Statistically, the incidence of acne vulgaris is comparable, but more severe course is more common in men. The most prone to acne are areas rich in sebaceous glands - face, including the T-zone, back, chest. The clinical picture is dominated by blackheads, pustules, papules, cysts, nodules, and inflammatory infiltrates. The etipathogenesis of acne is complex, and finding the cause is very difficult and time-consuming. Regardless of age, people suffering from acne experience great discomfort, which has a very negative impact on their self-esteem and quality of life.

The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy. [ABSTRACT FROM AUTHOR]

Recent data indicate that distinct skin areas show different microbial/chemical milieu. Keratinocytes (KC) respond to these stimuli by producing cytokine mediators. Therefore, we aimed to determine KC‐derived cytokine expression in distinct healthy skin regions (gland‐poor [GP], sebaceous gland‐rich [SGR] and apocrine gland‐rich [AGR]), and their changes in skin diseases of the given regions (atopic dermatitis [AD], papulopustular rosacea [PPR] and psoriasis). Cytokines were analysed at the mRNA and protein levels, and literature analysis was performed for functional categorization. The three regions showed characteristically different cytokine patterns. GP was featured by an IL‐25/IL‐33/IL‐36RA/IL‐38/IL‐18 cytokine milieu, SGR was characterized by IL‐23/IL‐17C/IL‐18, and AGR skin exhibited a mixed IL‐25/IL‐33/IL‐23/IL‐18 profile. Literature analyses revealed different homeostatic and proinflammatory roles of these cytokine patterns (Th2 related in GP, Th17 related in SGR and mixed Th2/Th17 in AGR). In skin diseases which are primarily epidermal cytokine‐driven (AD, PPR), the level of the regionally characteristic cytokines were further elevated, in contrast to the autoantigen‐driven psoriasis, where the cytokine pattern was independent from the localization. Healthy skin regions are equipped with different KC‐derived cytokine profiles, which may influence each region's capability of mediator production in certain types of dermatoses. [ABSTRACT FROM AUTHOR]

ABSTRACT: Skin and hair coat play important functions in maintaining homeostasis and thermoregulation for cattle, which can affect all modes of heat loss. Our objective was to investigate the effect of hyperthermia experienced in utero during late gestation on postnatal hair length, skin properties, and thermoregulation. Pregnant dams were heat stressed (n = 41) or actively cooled (n = 41) for the last ∼56 d of gestation and gave birth to heifers that were in utero heat stressed (IUHT) or in utero cooled (IUCL), respectively. Hair samples and skin tissue biopsies were collected from neck and rump locations at birth (d 0), 1 wk after weaning (d 63), and at 12 mo. Hair samples were also obtained at 4 and 8 mo. Skin tissue was stained with hematoxylin and eosin to visualize morphology. Hair length (short and long hairs, undercoat and topcoat, respectively), stratum corneum (SC) area, SC thickness, epidermis thickness, sweat gland (SWT) number, SWT cross-sectional area, SWT average size, sebaceous gland (SEB) number, SEB cross-sectional area, SEB average size, and sweat gland depth were assessed. Respiration rate, skin temperature, sweating rate, and rectal temperature was measured weekly from d 7 to 63. Additionally, thermoregulatory patterns were measured every 4 h over a 36-h interval beginning 4 d after weaning. Data were analyzed using PROC MIXED in SAS with a main effect of in utero treatment with location and time points analyzed separately. No difference in hair parameters were detected at d 0 or 12 mo. At d 63, IUHT heifers had longer average hair length (14.8 vs. 13.8 ± 0.2 mm, standard error), shorter undercoats (9.3 vs. 10.4 ± 0.3 mm), longer topcoats (19.6 vs. 17.1 ± 0.3 mm), and a greater difference between topcoat and undercoat (10.1 vs. 7.0 ± 0.4 mm). At 4 mo, IUHT heifers had longer average hair lengths (26.1 vs. 22.2 ± 1.0 mm) and longer topcoats (36.9 vs. 33.9 ± 1.1 mm), and at 8 mo, IUHT had longer average hair lengths (17.9 vs. 16.2 ± 0.6 mm), relative to IUCL. At d 0, IUHT heifers had more (13 vs. 9 ± 2 glands) but smaller average sized SEB (neck: 1,636 vs. 2,238 ± 243 µm2; rump: 2,100 vs. 3,352 ± 379 µm2) and reduced SC area (79,243 vs. 169,419 ± 13,071 µm2). At d 63, IUHT had fewer SEB (11 vs. 15 ± 2 glands), smaller SWT (0.16 vs. 0.23 ± 0.02 mm2), fewer SWT (16 vs. 23 ± 4 glands), and deeper SWT (0.5 vs. 0.4 ± 0.03 mm). At 12 mo, IUHT had greater distance from the skin surface to the most superficial SWT (0.016 vs. 0.015 ± 0.0004 mm), shorter distance to the deepest SWT (0.031 vs. 0.033 ± 0.001 mm), and smaller SWT (81.1 vs. 108.9 ± 10.8 µm2), relative to IUCL. When measured both weekly and hourly, IUHT heifers had higher rectal temperature and sweating rate. Overall, in utero hyperthermia triggers long-lasting hair and skin adaptations, possibly leading to differences in postnatal thermoregulation.

Insulin affects metabolic processes in different organs, including the skin. The sebaceous gland (SG) is an important appendage in the skin, which responds to insulin-mediated signals, either directly or through the insulin growth factor 1 (IGF-1) axis. Insulin cues are differently translated into the activation of metabolic processes depending on several factors, including glucose levels, receptor sensitivity, and sebocyte differentiation. The effects of diet on both the physiological function and pathological conditions of the SG have been linked to pathways activated by insulin and IGF-1. Experimental evidence and theoretical speculations support the association of insulin resistance with acne vulgaris, which is a major disorder of the SG. In this review, we examined the effects of insulin on the SG function and their implications in the pathogenesis of acne.

Background: The aim of this study was to explore the anti‐inflammatory and anti‐lipid effects of lactoferrin on SZ95 human sebaceous gland cells and mouse model of acne. Methods: SZ95 cells were co‐cultured with different concentrations of lactoferrin, and cell viability was determined using the 2,5‐diphenyl‐2H‐tetrazolium bromide method. Oil red O and Nile red staining were performed to determine the lipid content. The mRNA expression of genes related to lipid metabolism (sterol regulatory element‐binding protein‐1 [SREBP‐1], fatty acid synthase [FAS], stearoyl‐CoA desaturase‐1 [SCD‐1], fatty acid desaturase 2 [FADS2]) and inflammation (interleukin‐8 [IL‐8]) was determined by reverse transcription–polymerase chain reaction. An acne mouse model was established using injection of P. acnes on the backs of mice. The proliferation and apoptosis of sebaceous gland cells were examined by immunohistochemistry against proliferating cell nuclear antigen (PCNA) and TUNEL staining, respectively. Western blotting was used to detect FADS2 and CXCL15 protein expression. Results: Lactoferrin treatment at 10–500 μg/ml significantly decreased the lipid content, as revealed by the oil red O and Nile red staining. It also attenuated the increase of mRNA expression of SREBP‐1, FAS, SCD‐1, FADS2, and IL‐8 in insulin‐treated SZ95 cells. Moreover, lactoferrin treatment at the doses of 1–50 mg/mouse significantly reduced the inflammation and lipid production in the mouse model of acne. Also, the number of sebaceous gland cells was significantly reduced, and apoptosis was significantly increased by lactoferrin treatment in the mice. Mechanically, the levels of FADS2 and CXCL15 proteins in tissues were significantly decreased after lactoferrin treatment in the model mice. Conclusion: Our results demonstrate the potential of lactoferrin against sebogenesis, sebaceous gland inflammation in acne. [ABSTRACT FROM AUTHOR]

The document titled "Clinical Features and Treatment of Sebaceous Carcinoma: A Systematic Review" published in the Journal of Cutaneous Medicine & Surgery discusses the rare but potentially aggressive malignancy of sebaceous carcinoma. Risk factors include fair skin, older age, ultraviolet radiation, immunosuppression, and genetic syndromes like Muir–Torre syndrome. The study found that surgical excision was the predominant treatment, followed by Mohs micrographic surgery and orbital exenteration, with differences in treatment outcomes between sporadic and MTS-associated cases. Continued vigilance in recognizing SC features, especially in high-risk populations, is crucial for timely intervention and improved patient outcomes. [Extracted from the article]

BackgroundSebaceous gland hyperplasia (SGH) is a benign cutaneous proliferation of the sebaceous glands that are mostly present on the face or the neck of older adults. They typically appear as single or multiple soft umbilicated papules; however, in challenging cases, it can be difficult to distinguish them from trichoepitheliomas, base cell carcinomas, or other tumors. Although pathological results have diagnostic value, the significance of non-invasive examinations in diagnosis and differential diagnosis is also worth exploring.ObjectivesThis study aimed to describe the dermoscopic and reflectance confocal microscopy (RCM) features of SGH.MethodsA total of 31 patients diagnosed with SGH, according to clinical and histopathological standards, were examined using dermoscopy and RCM between March 2018 and January 2022.ResultsDermoscopically, lesions revealed a yellowish-red background and a faint-yellow background in 25 (80.65%) and six cases (19.35%), respectively. White-yellowish lobulated structures in the center of the lesion were present in 31 patients (100%) and umbilications in 19 patients (61.29%). Crown vessels at the periphery of the lesions were observed in 11 patients (35.48%), whereas irregular linear vessels were observed on the surface of the lesions in 18 patients (58.06%). Under RCM, all lesions presented a honeycomb pattern in the epidermis and the typical morulae-shaped sebaceous lobules in the dermis. A dilated follicular infundibulum was observed in 15 patients (48.39%) and dilated vessels in 26 patients (83.87%).ConclusionDermoscopy and RCM enabled us to describe the imaging features of SGH. Combining these two useful tools provides a non-invasive basis for accurate clinical diagnosis.

Lipids synthesized on the skin are critical to the antimicrobial barrier. Skin lipids also facilitate survival of lipophilic skin commensals in an otherwise dry and acidic ecological landscape. Thus, skin‐specific stearoyl‐coenzyme A desaturase 1 knockout mice (Scd1ΔK14) with sebocyte atrophy and decreased synthesis of monounsaturated fatty acids, triglycerides and wax diesters have dry, inflamed skin. Here, we used 16S rRNA (V1‐V2 and V1‐V9) and internal transcribed spacer 1 (ITS1) amplicon sequencing to compare bacterial and fungal skin microbiomes between Scd1ΔK14 mice and wildtype control mice (Scd1fl/fl) in a barrier facility. Saprophytic bacteria including Sporosarcina spp. and Staphylococcus lentus and saprophytic fungi including Alternaria infectoria were found in higher relative abundance in the Scd1ΔK14 group (ANCOM). Analysis of community diversity (Shannon index) revealed greater fungal alpha diversity in the Scd1ΔK14 group (p = 0.009, Kruskal–Wallis). Principal coordinates analysis (Bray–Curtis dissimilarity) showed that both bacterial (p = 0.002, PERMANOVA) and fungal communities (p = 0.006, PERMANOVA) of the Scd1ΔK14 group were unique from the wildtype group. Altogether, these results suggest that sebaceous gland‐derived lipids normally restrict the skin microbiome, and in the absence of these lipids, a greater diversity of opportunistic organisms are able to colonize the surface of skin. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a well-recognized condition among adolescents and adults that adversely affects their quality of life. Local cryotherapy has long been reported to be effective in treating acne vulgaris, inducing a more rapid involution of acne than topical medications. However, the use of cryotherapy has been limited for acne treatment due to several drawbacks, including procedural pain and pigmentary alterations. Currently, newer cryotherapy devices are gaining attention in dermatology due to their ability to monitor and precisely control the target temperature. In this narrative review, a brief history and the latest update on acne cryotherapy will be presented. Additionally, a special emphasis is placed on the role of cryotherapy, alone or in combination with intralesional steroid injections for nodulocystic acne. [ABSTRACT FROM AUTHOR]

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Skin is the largest organ of the body, accounting for 15-20% of the total body weight and acts as a barrier between the external and internal environment and maintain homeostasis. The sweat and sebaceous glands in dermis of skin play vital role in developing the adaptive ability to the heat stress. Besides this, the distribution pattern and number of these glands vary in different animals that may aid in identification of different species. Methods: The study was conducted on abdominal skin of 36 adult cattle, buffalo, horse, goat, pig and dog (six sample of each) collected from abattoir, Veterinary clinics and post-mortem hall of GADVASU, Ludhiana. After collection, the tissues were fixed in 10% neutral buffered formalin and processed for paraffin block preparation. The paraffin sections of 5-6 µm were cut and stained with hematoxylin and eosin stain. Result: The study revealed that the sebaceous glands were multilobular, alveolar glands comprised of several layers of epithelial cells and were associated with hair follicles in all species studied. The number of sebaceous glands/mm² was significantly higher (p≤0.05) in goat (1.60± 0.11) than in pig (0.44±0.06) whereas sebaceous gland diameter was significantly higher (p≤0.05) in buffalo (109.83±6.14 µm) than in goat (61.16±2.42 µm). The sweat glands were of saccular and simple coiled tubular type and most of them were associated with hair follicles. The number of sweat glands/mm² was the highest in horse (3.10±0.24) and the least in buffalo (0.76 ±0.05). Sweat gland diameter was significantly higher (p≤0.05) maximum in buffalo (123±3.15 µm) and minimum in goat (50.33±2.85 µm) and the difference. [ABSTRACT FROM AUTHOR]

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis.

Background: Acne is a multifactorial disease, in the pathogenesis of which one of the leading factors is the excessive effect of androgens on the hair follicles (HFs) and sebaceous glands (SGs), along with hypersecretion of sebum, pathological follicular hyperkeratosis and an inflammatory response. The search for genotypic markers in patients with varying severity of acne is a difficult task due to the multifactorial pathogenesis and the role of trigger factors in the formation of acne. The aim of this study was to determine SNPs within 3 genes involved in steroidogenesis (MVK, ARPC1B, and CA2) in patients with severe acne. Methods and Results: The study included 70 patients (42 men and 28 women) aged between 15 and 46 years (the median age - 22.1 years). The main group (MG) included 50 patients (29 men and 21 women) with severe acne. The control group (CG) consisted of 20 apparently healthy individuals (13 men and 7 women). Molecular-genetic diagnostics was carried out by the method of high-throughput DNA sequencing (next-generation sequencing). Our study showed that severe acne is associated with 12 polymorphic loci of the MVK gene (4 SNPs in exons and 8 SNPs in introns), 7 SNPs of the ARPC1B gene (2 SNPs in exons and 5 SNPs in introns), and 9 SNPs of the CA2 gene (3 SNPs in exons and 6 SNPs in introns). Conclusion: The revealed features of the SNPs within the MVK, ARPC1B, and CA2 genes in patients with severe acne probably indicate a hereditary determination of steroidogenesis in acne.

The fatty acid composition in the skin of Sunda porcupine (Hystrix javanica) is an interesting topic due to the special features of quills, especially in the dorsal region. Therefore, this study aims to analyze the composition of fatty acids in the dorsal region of Sunda porcupine skin. It was conducted using skin samples of the thoracodorsal and lumbosacral regions taken by biopsies and from frozen specimens. The skin lipid was extracted and then derivatized into fatty acid methyl ester before analyzing with gas chromatography mass spectrometry. The results showed that the skin is composed of up to 25 fatty acids ranging from C12 to C25 with various types but only 16 were found in both regions and sexes. Fatty acids with an antibacterial effect were found abundantly, such as oleic, palmitic, stearic, and linoleic acids. The total abundance in the thoracodorsal region was higher than lumbosacral, while the composition in male was higher than in female. Based on the results, the fatty acid composition in the dorsal skin region of Sunda porcupine consists of at least 16 types ranging from C12-C25. Additionally, the region and sex were observed to contribute significantly to the variation in skin fatty acid composition. [ABSTRACT FROM AUTHOR]

The effects of androgens on human skin mainly include the regulation of growth and differentiation of hair follicles and sebaceous glands. Androgens may have some physiological roles in sheep skin that are similar to those of humans, but further confirmation is needed. Therefore, Hetian sheep were chosen in this study as an animal model to explore the effects of testosterone on skin structure and factors related to androgen conversion and binding in Hetian sheep. The sheep were treated with different concentrations of testosterone for 42 days. Skin tissue sections were prepared and then subjected to hematoxylin–eosin, Sacpic, Masson’s trichrome, and Oil Red O staining to observe changes in skin morphology. Changes in the content of blood-related factors were also detected using ELISA kits. The skin tissue distribution of androgen receptor was explored by immunohistochemistry and immunofluorescence assays. The results showed that testosterone significantly increases the sebaceous gland area and stimulates the formation of new sebaceous glands. Further exploration revealed that testosterone promotes the proliferation of sebaceous gland juvenile cells. However, testosterone was found to have no significant effect on hair follicle density and hair follicle structure. Testosterone increased dihydrotestosterone levels but decreased 5α-reductase 1 and 5α-reductase 2 levels. The androgen receptors were distributed in the hair follicles, sebaceous glands, and some major skin appendages of Hetian sheep. This study suggests that androgens can be effective in regulating sebum production in sheep. This study will help advance research efforts to further explore the molecular and cellular mechanisms by which androgens modify sheep follicles and sebaceous glands. [ABSTRACT FROM AUTHOR]

Introduction: As a rule, the treatment of pilonidal cysts is based on a surgical approach. Surgical treatment depends on the form of the disease and surgeon's preferences regarding the method. The treatment process does not consider preoperative treatment that would affect the structural components of the skin involved in the pathological process. The results of surgical treatment remain unsatisfactory, leading to a significant number of recurrences and long-term healing of the postoperative wound. Materials and methods: Morphological examination of the pieces of skin with altered sacrococcygeal tissues after radical surgical treatment of 46 patients with pilonidal cyst of the sacrococcygeal region was performed, and 46 patients with acne inversa of the intergluteal cleft, groin and scalp were selected. The sex distribution of patients with pilonidal cysts was as follows: 43 (91.3%) male patients, 3 (6.5%) female patients. Among 46 patients with acne inversa and dissecting cellulitis, the distribution was as follows: 32 (69.6%) male patients and 14 (30.4%) female patients. Patients with pilonidal cysts of the sacrococcygeal region underwent surgical treatment according to the developed method of economical median resection using sutures with internal fixation. Results: Considering and comparing the morphological picture observed in the pathomorphological examination of histological specimens in patients with pilonidal cysts, acne inversa, dissecting cellulitis, the similarity of changes in most patients is noteworthy. “Acne inversa” was first described in 1839 by Velpeau, who originally called the disease “hydradenitis suppurativa”, believing that inflammatory changes occur in the sweat glands [1–3]. In 1854, surgeon Verneuil described this disease, and later it was named after him. We observed chronic proliferative inflammation in different layers of the dermis and subcutaneous tissue (the main focus is in the subcutaneous tissue, but closely related to the dermis and epidermis). Discussions: Pilonidal cyst of the sacrococcygeal region, especially without hair in the cavity of the cyst, can be considered as a type of acne inversa with appropriate location. We believe that the use of local and systemic retinoids, namely isotretinoin, in the treatment of patients with this disease other than surgery, together with other groups of drugs traditionally used in the treatment of pilonidal cysts, may be promising in the treatment of pilonidal cysts. [ABSTRACT FROM AUTHOR]

Sebaceous glands (SGs) originate from hair follicular stem cells and secrete lipids to lubricate the skin. The coordinated effects of intrinsic and extrinsic aging factors generate degradation of SGs at a late age. Senescence of SGs could be a mirror of the late aging of both the human body and skin. The procedure of SG aging goes over an initial SG hyperplasia at light-exposed skin areas to end with SG atrophy, decreased sebum secretion, and altered sebum composition, which is related to skin dryness, lack of brightness, xerosis, roughness, desquamation, and pruritus. During differentiation and aging of SGs, many signaling pathways, such as Wnt/β-catenin, c-Myc, aryl hydrocarbon receptor (AhR), and p53 pathways, are involved. Random processes lead to random cell and DNA damage due to the production of free radicals during the lifespan and neuroendocrine system alterations. Extrinsic factors include sunlight exposure (photoaging), environmental pollution, and cigarette smoking, which can directly activate signaling pathways, such as Wnt/β-catenin, Notch, AhR, and p53 pathways, and are probably associated with the de-differentiation and hyperplasia of SGs, or indirectly activate the abovementioned signaling pathways by elevating the inflammation level. The production of ROS during intrinsic SG aging is less, the signaling pathways are activated slowly and mildly, and sebocytes are still differentiated, yet terminal differentiation is not completed. With extrinsic factors, relevant signaling pathways are activated rapidly and fiercely, thus inhibiting the differentiation of progenitor sebocytes and even inducing the differentiation of progenitor sebocytes into keratinocytes. The management of SG aging is also mentioned.

Abstract Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6bri/CD71dim expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs. Methods The α6bri/CD71dim cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells. Results EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice. Conclusions Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.

To establish the optimal amount of nutrients in the diets required for the pregnant sheep, in the conditions of the distant-mountain keeping of the North Caucasus in 2018, after tupping, 120 Tushin ewes were selected for the third lambing, which were divided into four groups 30 heads each. Ewes of the control group received a food ration prepared in accordance with the standards of the All-Russian Research Institute of Animal Husbandry (VIZH) (2003). The ration of the second, third and fourth groups of ewes was increased in total nutritional value by 10%, 15% and 20%, respectively, compared with the diet of the control group. The study of skin structure was carried out using prepa-rations made from pregnant ewe skin samples taken from five heads from each group. It was found that, depending on the season of the year and severity, the skin of the experimental ewes underwent significant changes: the thickness of the skin and its layers decreased, the activity of sweat and se-baceous glands decreased, the hair follicles and the diameter of the collagen fiber bundles de-creased in size. The greatest decrease in these parameters occurred in the skin of ewes that were pregnant and received a diet prepared in accordance with the VIZH standards (17.1%). Similar chang-es occurred in the thickness of the epidermis, pilar and reticular layers. The smallest decrease in the thickness of the skin and its layers occurred in the group of ewes under high feeding conditions. The study of horizontal sections of the skin of the experimental groups of ewes showed that the level of feeding during the lambing period did not affect the number of follicles in the hair group. In the groups of ewes that received an increased level of feeding, the number of follicles per unit of skin area decreased by 8.0-13.9%, which is associated with an increase in body condition and, according-ly, an increase in skin area.

We here report a peculiar case of ACD due to hydroquinone (HQ), clinically presenting as frog egg-like dermatitis, histologically characterized by lymphocytic infiltrates confined to the sebaceous glands. Keywords: case report; hydroquinone; noneczematous allergic contact dermatitis; perifollicular contact dermatitis; sebaceous gland EN case report hydroquinone noneczematous allergic contact dermatitis perifollicular contact dermatitis sebaceous gland 160 162 3 01/13/23 20230201 NES 230201 Atypical clinical and histological cases of allergic contact dermatitis (ACD) have been occasionally reported. Case report, hydroquinone, noneczematous allergic contact dermatitis, perifollicular contact dermatitis, sebaceous gland. [Extracted from the article]

Topical 17-beta-estradiol (E2) regulates the hair cycle, hair shaft differentiation, and sebum production. Vitamin A also regulates sebum production. Vitamin A metabolism proteins localized to the pilosebaceous unit (PSU; hair follicle and sebaceous gland); and were regulated by E2 in other tissues. This study tests the hypothesis that E2 also regulates vitamin A metabolism in the PSU. First, aromatase and estrogen receptors localized to similar sites as retinoid metabolism proteins during mid-anagen. Next, female and male wax stripped C57BL/6J mice were topically treated with E2, the estrogen receptor antagonist ICI 182,780 (ICI), letrozole, E2 plus letrozole, or vehicle control (acetone) during mid-anagen. E2 or one of its inhibitors regulated most of the vitamin A metabolism genes and proteins examined in a sex-dependent manner. Most components were higher in females and reduced with ICI in females. ICI reductions occurred in the premedulla, sebaceous gland, and epidermis. Reduced E2 also reduced RA receptors in the sebaceous gland and bulge in females. However, reduced E2 increased the number of retinal dehydrogenase 2 positive hair follicle associated dermal dendritic cells in males. These results suggest that estrogen regulates vitamin A metabolism in the skin. Interactions between E2 and vitamin A have implications in acne treatment, hair loss, and skin immunity. [ABSTRACT FROM AUTHOR]

MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology. [ABSTRACT FROM AUTHOR]

• An immortalized sebaceous gland cell line (XL-i-20) derived from asian samples was firstly constructed, which retained the parental characteristics and demonstrated increased cell viability. • Both XL-i-20 sebocytes and primary sebocytes exhibited similar responsiveness to ALA-PDT, with upregulated inflammation and inhibited sebum production observed after the treatment. • The proliferation of sebaceous gland organoids derived from XL-i-20 cells was inhibited post ALA-PDT. Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown. To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT. Human primary sebocytes were transfected with the human tert gene (h‑tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT. The h‑tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT. We have developed an h‑tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases. [ABSTRACT FROM AUTHOR]

Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with the interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, Abca12 , which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell-autonomous responses in the epidermis. Third, deleting Abca12 in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing IL-17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function. [Display omitted] • Abca12 is a canonical skin barrier gene mutated in harlequin ichthyosis • Conditional deletion of Abca12 provides a potent genetic tool to probe barrier function • Hair follicles exert multi-faceted control over the skin's barrier • Deleting Abca12 in Krt79+ upper hair follicle cells causes ichthyosis-associated phenotypes Skin usually comprises both follicular and interfollicular epithelia. Most studies on skin barrier function focus on the interfollicular epidermis without considering the role of the follicular epithelium. Using a targetable genetic tool to disrupt barrier function, Ford et al. identify multiple ways by which hair follicles modulate the skin's barrier. [ABSTRACT FROM AUTHOR]

James Nicoll, Benjamin M Buehrer Zen-Bio, Inc., Research Triangle Park, NC, USACorrespondence: Benjamin M BuehrerZen-Bio, Inc., 3200 East Highway 54, Suite 100, PO Box 13888, Research Triangle Park, NC 27709, USATel +1 919 547 0692Fax +1 919 547 0693Email ben@zenbio.comIntroduction: Acne arises during puberty, in part, due to elevated hormones and growth factors which stimulate de novo lipogenesis (DNL) in primary sebocytes to significantly increase sebum production. Oral isotretinoin is an effective acne therapy, reducing sebum production through inducing apoptosis in sebocytes. However, isotretinoin is teratogenic and has additional unwanted side effects, including an initial acne flare-up, which limits its utility. The biguanide, metformin has been found to alleviate severe acne in women with polycystic ovary syndrome (PCOS) through normalization of their insulin and androgen hormone levels. Metformin’s broader effectiveness to improve acne in non-PCOS populations lacks significant clinical support. In an effort to determine whether biguanides directly affect sebogenesis, we investigated their ability to alter DNL in cell-based assays in vitro.Methods: De novo lipogenesis was measured in human primary sebocytes using [14C]-acetate labeling. Lipid species analysis was performed by extracting newly synthesized lipids and subjecting them to thin layer chromatography. Gene expression changes in sebocytes were identified through qPCR analysis of isolated RNA. Metabolic parameters including oxygen consumption rate, lactate production and activation of adenosine monophosphate-dependent protein kinase (AMPK) were assessed in human primary sebocytes.Results: Using human primary sebocytes, we found that biguanides, isotretinoin and azithromycin induced an acute dose and time-dependent increase in [14C]-acetate labeling of neutral lipids, while AICAR, an AMPK activator, inhibited this DNL response. Biguanides did not activate AMPK in sebocytes, however, they significantly reduced oxygen consumption rate and increased lactate production. Treatment with biguanides, but not isotretinoin, significantly upregulated ACSS2 gene expression in primary sebocytes and showed synergism with lipogenic activators to induce DNL genes.Discussion: These changes are consistent with an acute increase in sebocyte lipogenesis and support the potential of biguanides to cause an initial flare-up in patients suffering from severe acne.Keywords: sebocytes, acne, metformin, de novo lipogenesis, sebaceous gland

Muir-Torre Syndrome is characterized by the association of sebaceous gland neoplasms and multiple visceral neoplasms. There are several types of visceral neoplasms that can be associated with the syndrome, especially adenocarcinomas of the colon, stomach, duodenum, breast, laryngeal, bladder tumors, hematologic neoplasms, retroperitoneum sarcomas, among others. The general objective of the work is to study aspects of Muir- Torre Syndrome. Therefore, a literature review was carried out, seeking authors who spoke about the proposed theme. The objective is also to report the case of a patient at the Hospital Escola de Valença (HEV), located in the city of Valença - RJ, who presented a year ago in a cyst back filled with bloody purulent secretion, who upon receiving the biopsy result, after exeresis of the cyst, with diagnosis of sebaceous carcinoma, was referred to Hospital Hinja, located in the city of Volta Redonda -- RJ. The patient has a history of malignant neoplasms in firstdegree relatives. The mother died of uterine cancer, the sister died of bowel cancer and the maternal grandmother of bowel cancer. The discussion is based on the correlation between sebaceous carcinoma and Muir-Torre Syndrome, as according to literature data, the factors that predispose the appearance of sebaceous carcinoma are unknown, however, some cases are associated with Muir-Torre Syndrome. The study verifies that the presence of multiple sebaceous gland tumors is the most constant dermatological manifestation that most characterizes Muir-Torre Syndrome. [ABSTRACT FROM AUTHOR]

Background: Despite their widespread clinical use in both acne vulgaris and rosacea, the effects of tetracyclines on sebocytes have not been investigated until now. Sebaceous glands are central to the pathogenesis of acne and may be important in the development of rosacea. Objective: The aim of this study was to assess the effects of doxycycline on the immortalized SZ95 sebaceous gland cell line as a model for understanding possible effectiveness on the sebaceous glands in vivo. Methods: The effects of doxycycline on SZ95 sebocyte numbers, viability, and lipid content as well as its effects on the mRNA levels of peroxisome proliferator-activated receptors α and γ, in comparison to the peroxisome proliferator-activated receptor γ agonist troglitazone, were investigated. Results: Doxycycline reduced the cell number and increased the lipid content of SZ95 sebocytes in vitro after 2 days of treatment. These doxycycline effects may be explained by an upregulation of peroxisome proliferator-activated receptor γ mRNA levels at 12 and 24 h, whereas troglitazone already upregulated peroxisome proliferator-activated receptor γ levels after 6 h. Both compounds did not influence peroxisome proliferator-activated receptor α mRNA levels. Conclusion: These new findings illustrate a previously unknown effect of doxycycline on sebocytes, which may be relevant to their modulation of disorders of the pilosebaceous unit, such as acne vulgaris and rosacea. [ABSTRACT FROM AUTHOR]