Search

Introduction: The role of the eyelids is to protect and moisturise the eye. Despite its small relative surface area, 5-10% of skin cancers originate in the eyelids. Aim: To assess the prevalence of different types of skin lesions in the area of eyelids based on retrospective histopathology data from a tertiary centre. Material and methods: Among 544 included eyelid lesions, 429 (79%) were benign and 115 (21%) were malignant. In the benign group, the most common finding was a chalazion (49.2%) followed by squamous papilloma (22.8%), seborrheic keratitis (10%), epidermal cyst (8.2%), and intradermal nevus (5.1%). Out of all malignant lesions, the most common diagnosis was basal cell carcinoma (BCC) in 110 (95.7%) patients. Results: Squamous cell carcinoma (SCC) was diagnosed in 3 (2.6%) patients and sebaceous gland carcinoma (SGC) in 2 (1.7%). No malignant melanoma was identified in the studied group. Conclusions: Although benign lesions are the most common eyelid tumours, it is essential to differentiate between benign and malignant eyelid tumours because early detection and appropriate treatment may improve the cosmetic effect and reduce recurrences. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a worldwide condition that has a complex pathophysiology. The knowledge of this pathology is clear in its four classic principles based on the pilosebaceous unit; there exists hyperkeratinization of its duct, increase of sebum production, anaerobic bacterias, and inflammatory response. However, new findings have explained the relationship that occurs inside the acne lesion. The immune system has a key role since it is stimulated by the other participants involved, such as phylotypes of Propionibacterium acnes (P. acnes), antimicrobial peptides (AMPs), sebaceous glands (SGs), matrix metalloproteinases (MMPs), and other immune system pathways. [ABSTRACT FROM AUTHOR]

Sarecycline is a narrow-spectrum antibiotic for the treatment of acne, which is a chronic inflammatory disease of the hair follicle sebaceous glands. In the study, UPLC-MS/MS was used to establish a rapid and accurate analytical method. The sarecycline was determined with poziotinib as internal standard (IS) in rat plasma. An ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) could performe chromatographic separation with the mobile phase (methanol: water of 0.1% formic acid) with gradient elution. The ions of target fragment were m/z 488.19→410.14 for sarecycline and m/z 492.06→354.55 for poziotinib, which could quantify the electrospray ionization of positive multiple reaction monitoring (MRM) mode. The linear calibration curve of the concentration range was 1–1,000 ng/mL for sarecycline with a lower limit of quantification (LLOQ) of 1 ng/mL. The mean recovery was between 82.46 and 95.85% for sarecycline and poziotinib in rat plasma. RSD for precision of inter-day and intra-day were between 3.24 and 13.36%, and the accuracy ranged from 105.26 to 109.75%. The developed and validated method was perfectly used in the pharmacokinetic study and bioavailability of sarecycline after intravenous and oral administration in rats. [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]

The label-free methods of proteomic combined with metabolomics were applied to explore the mechanisms of Cryptotanshinone (CPT) intervention in rats with acne. The model group consisted of rats given oleic acid (MC), then treated with CPT, while control groups did not receive treatment. The skin samples were significantly different between control, model and CPT-treated groups in hierarchical clustering dendrogram. Obvious separations of the skin metabolic profiles from the three groups were found through PCA scoring. In total, 231 and 189 differentially expressed proteins (DEPs) were identified in MC and CPT groups, respectively. By the KEGG analysis, five protein and metabolite pathways were found to be significantly altered. These played important roles in response to oleic acid-induced acne and drug treatment. CPT could negatively regulate glycolysis/gluconeogenesis and histidine metabolisms to decrease keratinocyte differentiation and improve excessive keratinization and cellular barrier function. CPT could down-regulate the IL-17 signaling pathway and regulate the acne-driven immune response of sebum cells. The biosynthesis of unsaturated fatty acids metabolism, glycerophospholipid metabolism and linoleic acid pathways could significantly alter sebum production and control sebaceous gland secretion after CPT treatment. The gap junction was up-regulated after CPT treatment and the skin barrier turned back to normal. Krt 14, Krt 16 and Krt 17 were significantly down-regulated, decreasing keratinization, while inflammatory cell infiltration was improved by down-regulation of Msn, up-regulation of linoleic acid and estrogen pathways after CPT treatment. These results propose action mechanisms for the use of CPT in acne, as a safe and potential new drug. [ABSTRACT FROM AUTHOR]

Although keratosis pilaris (KP) is common, its etiopathogenesis remains unknown. KP is associated clinically with ichthyosis vulgaris and atopic dermatitis and molecular genetically with filaggrin-null mutations. In 20 KP patients and 20 matched controls, we assessed the filaggrin and claudin 1 genotypes, the phenotypes by dermatoscopy, and the morphology by light and transmission electron microscopy. Thirty-five percent of KP patients displayed filaggrin mutations, demonstrating that filaggrin mutations only partially account for the KP phenotype. Major histologic and dermatoscopic findings of KP were hyperkeratosis, hypergranulosis, mild T helper cell type 1-dominant lymphocytic inflammation, plugging of follicular orifices, striking absence of sebaceous glands, and hair shaft abnormalities in KP lesions but not in unaffected skin sites. Changes in barrier function and abnormal paracellular permeability were found in both interfollicular and follicular stratum corneum of lesional KP, which correlated ultrastructurally with impaired extracellular lamellar bilayer maturation and organization. All these features were independent of filaggrin genotype. Moreover, ultrastructure of corneodesmosomes and tight junctions appeared normal, immunohistochemistry for claudin 1 showed no reduction in protein amounts, and molecular analysis of claudin 1 was unremarkable. Our findings suggest that absence of sebaceous glands is an early step in KP pathogenesis, resulting in downstream hair shaft and epithelial barrier abnormalities.

Background: Muir–Torre syndrome (MTS), which accounts for a small subset (1–3 %) of Lynch syndrome (LS), is an autosomal dominant genetic disorder characterized by sebaceous gland or keratoacanthoma associated with visceral malignancies. Most families with MTS have pathogenic germline variants (PGV) in MSH2. Sarcomas are not common on the LS tumor spectrum, and sarcomas associated with MTS are extremely rare. Case presentation: Here we report a myxofibrosarcoma of the abdominal wall in a 73-year-old man with a sebaceoma that occurred synchronically, leading to a diagnosis of MTS. The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV. Conclusions: This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS. [ABSTRACT FROM AUTHOR]

Sebaceous carcinoma is a malignant neoplasm that usually arises in the sebaceous glands of the eyelids. Its pathogenesis is unknown; however, irradiation history, immunosuppression, and use of diuretics are known risk factors. The mainstay of treatment for sebaceous carcinoma of the eyelid is wide surgical resection with a safety margin of 5 to 6 mm, which often results in fullthickness defects. The reconstruction of a full-thickness defect of the eyelid should be approached using a three-lamella method: a mucosal component replacing the conjunctiva, a cartilage component for the tarsal plate, and a flap or skin graft for the skin of the eyelid. In this case, a fullthickness defect of the upper eyelid was reconstructed after tumor removal using a combination of a nasal septum chondromucosal composite graft and a forehead transposition flap, also known as a "Fricke flap." The flap was designed to include a line of the eyebrow on the lower margin of the flap to replace the eyelash removed during tumor excision. The wound healed completely, without any early or late complications, and the outcome was satisfactory. [ABSTRACT FROM AUTHOR]

The mites Demodex folliculorum (Simon) and Demodex brevis Akbulatova are part of the regular human skin fauna, found in the pilosebaceous unit, and their infestations might cause the disease known as demodicosis. Inflammatory response is triggered by this interaction in patients, causing the appearance of several facial dermatoses. In the present revision, mites will be characterized and their association with dermatological diseases shall be discussed, as well as diagnostic methods, immune response to their infestations, and the major treatments used for Demodex-related cases. Demodex infestations both in hair follicles (D. folliculorum) and in sebaceous glands (D. brevis) might lead to the aggravation of dermato-facial pathologies, and trigger a local inflammatory reaction in many cases, associated with mite density and their potential as vectors of pathogenic microorganisms. The treatments for these Demodex-associated pathologies have proven to be effective, particularly in decreasing density, and consequently, in mitigating symptoms and the overall patient clinical condition. [ABSTRACT FROM AUTHOR]

Background: Skin adnexal tumors (SATs) encompass a very broad variety of rare dermatopathologic entities. Objective: The aim of the present study was to analyze an incidence and clinicopathological findings of patients with biopsy-proven ASTs. Material and Methods: A retrospective review of all consecutive cutaneous tumors that were diagnosed at the Martin Biopsy Center in Martin from July 2019 to March 2021 was carried out. ASTs have been searched for from this file and studied based on their histologic type and line of differentiation, anatomic distribution, age, and gender. Results: Among over 3,700 skin tumors a total of 38 ASTs in 38 individuals (21 males, 17 females) have been found. The age of the patients ranged from 22-89 years (mean 55.5 y.). The head and neck region was found to be the most common site affected (26/38; 68.4%), followed by extremities (8/38; 21.1%) and trunk (4/38; 10.5%). Tumors of hair follicle origin constituted the largest category (22/38; 57.9%), followed by sweat gland tumors (15/38; 39.5%) and tumors derived from sebaceous glands (1/38; 2.6%). Benign lesions accounted for all 38 cases. Trichoepithelioma was the most frequent lesion found in the category of follicular tumors and poroma was the most common among tumours with sweat gland differentiation. Conclusion: An overall incidence of ASTs is low and in this institutional study they constituted about 1% of all cutaneous neoplasms. ASTs display a marked phenotypic heterogeneity, that is why many published studies have provided divergent results concerning their clinicopathological features. [ABSTRACT FROM AUTHOR]

Background: Filaggrin is a protein integral to the structure and function of the epidermis. Filaggrin (FLG) loss‐of‐function (LOF) mutations are common and increase the risk of developing atopic dermatitis (AD) and ichthyosis vulgaris (IV). Epidemiologic data suggest a link between skin cancer and AD. We examined if FLG staining pattern can be used to characterize cutaneous squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and reactive squamous epithelium. Methods: Tissue microarrays (TMAs) were created from 196 cases of formalin‐fixed paraffin‐embedded (FFPE) SCC and 144 BCC cases. TMAs and sections of reactive squamous epithelium were stained with optimized anti‐FLG antibody and evaluated for FLG expression (normal, abnormal, or negative). Results: FLG was absent in poorly differentiated (PD) compared to well‐differentiated (WD) SCC (P <.0001) and moderately‐differentiated (MD) (P =.0231) SCC, and in MD compared to WD SCC (P =.0099). Abnormal staining was significantly increased in PD compared to WD cases (P =.0039) and in MD compared to WD cases (P =.0006). Most BCC did not exhibit FLG expression (P <.05). Reactive squamous epithelium demonstrated normal, but exaggerated FLG expression. Conclusions: Our findings demonstrate the differences in FLG expression patterns in types of keratinocyte carcinomas and their mimickers. [ABSTRACT FROM AUTHOR]

Evidence for the effectiveness of metformin in the treatment of acne is limited. To assess its efficacy, comedones were experimentally induced in young New Zealand rabbit ear using Isopropyl Myristate (IM) followed by metformin treatment (30 mg/kg bodyweight) for 60 days with continued IM application. In another group, to check whether metformin pre‐treatment affects subsequent comedone development by IM, metformin was given for 14 days and then withdrawn (14 days) followed by comedone development with IM and metformin treatment. At different time points, dermatoscopic images of rabbit ear were taken for clinical assessment. Blood and biopsy samples were taken for hormonal assessment, histological examination and gene expression. Histologically confirmed acne model was developed in rabbit ear. Follicular size increased significantly (p = 0.0004 in both groups) upon IM application. Metformin significantly decreased comedones size as observed in dermatoscopic (p = 0.0003 in group I, p = 0.0190 in group II) and histological examination (p = 0.0313 in group I and II). However, size of comedones developed after metformin pretreatment was significantly (p < 0.0001) smaller. The lipid content of sebaceous glands decreased with metformin without any significant changes in the assessed hormones and genetic expression. Overall, metformin was found to be clinically effective in experimentally induced acne and can be used in humans. [ABSTRACT FROM AUTHOR]

The sebaceous gland (SG) is involved in different inflammatory, infectious and neoplastic processes of the skin and can be related to specific diseases, e.g., diabetes mellitus. Sometimes, the histological diagnosis requires complementary tests due to the ability of diseases to mimic other tumors. We evaluated the sebaceous gland density in Non-obese diabetic mice to analyze the N-acetylcystein effects and swimming exercise treatment in sebaceous glands healing, using specific staining in histochemistry and immunohistochemistry reactions in the identification of the lipid expression in the sebaceous gland. We investigated the intracytoplasmic lipid expression and analysis of gland density from SG in dorsal skin samples from the Non-obese diabetic (NOD mice) and diabetic animals submitted to antioxidant treatment and physical exercise. For histological analysis of the sebaceous glands, specific staining in histochemistry with sudan black and immunohistochemistry reaction with adipophilin were used in the evaluation. Statistical analysis showed significant proximity between the values of the control group and the diabetic group submitted to the swimming exercise (DS group) and similar values between the untreated diabetic group (UD group) and diabetic group treated with the antioxidant N-acetylcysteine (DNa group), which did not prevent possible differences where p < 0.01. Adipophilin (ADPH) immunohistochemistry permitted more intense lipid staining in SGs, the preservation of the SG in the control group, and a morphological deformed appearance in the UD and DNa groups. However, weak morphological recovery of the SG was observed in the DS-Na group, being more expressive in the DS group. In conclusion, the groups submitted to physical exercises showed better results in the recovery of the analyzed tissue, even being in the physiological conditions caused by spontaneous diabetes. [ABSTRACT FROM AUTHOR]

Objective: Seborrheic dermatitis (SD) is a common chronic inflammatory skin disorder characterized by erythematous papulosquamous lesions in body regions that are rich in sebaceous glands, particularly the scalp, face, and intertriginous areas. Seasonal variation has been reported in different skin diseases; however, the results have been contradictory. The aim of this research was to analyze the demographic characteristics of patients with SD and to examine the impact of seasonality. Methods: Patients who were diagnosed with SD at an outpatient dermatology clinic between June 1, 2015 and June 1, 2020 were included in this retrospective, cross-sectional, single-center, hospital-based study. Both pediatric and adult dermatology outpatient cases were evaluated. Results: A total of 2656 patients with SD presented at the outpatient clinic during the study period. The mean age was 31.99±15.88 years (range: 0--87 years). Among these patients, 1540 (58%) were males and 1116 (42%) were females. SD was most common among those aged 20--30 years (29.9%). The mean age was 29.51±15.43 years in the female patients and 33.80±15.96 in males. Evaluation according to season revealed that 817 (31%) patients presented during the winter months, 615 patients in spring (23%), 452 in summer (17%), and 772 (29%) in the autumn. Conclusion: SD is a common, multifactorial skin disease. This study evaluated a wide patient profile and it was observed that middle-aged adults and men were the most affected. Patients presented most frequently during the cold weather season. Although the data obtained from this study are similar to others in the existing literature, these findings provide a new contribution to the epidemiological data of Turkey. Prospectively designed, population- based studies that evaluate potential triggering factors will help to explain the full etiology and seasonal incidence more clearly. [ABSTRACT FROM AUTHOR]

Drug‐induced psoriasiform alopecia is an increasingly recognized form of alopecia mostly reported in association with TNF‐alpha inhibitors. However, drug‐induced psoriasiform alopecia in association with IL‐17A inhibitors has not been described. We present a 62‐year‐old woman with severe psoriasis who developed new psoriatic plaques on the scalp with alopecia after initiating ixekizumab (anti‐IL‐17A). Scalp biopsy specimens revealed a non‐cicatricial alopecia with increased telogen/catagen follicles, atrophy of the sebaceous glands, peribulbar and perifollicular inflammation with frequent lymphocytes, plasma cells, eosinophils, psoriasiform dermatitis, and lack of intra‐corneal or intra‐epidermal neutrophils. Overall, the clinical and histopathologic findings were most compatible with a drug‐induced psoriasiform alopecia in association with IL‐17A inhibitor therapy. Our case shows that drug‐induced psoriasiform alopecia can paradoxically occur in patients on IL‐17A inhibitor therapy and contributes to the growing list of cutaneous eruptions associated with biologic agents. [ABSTRACT FROM AUTHOR]

Esophageal ectopic sebaceous glands are very rare lesions. A series of 5 cases in a single report has been the maximum number described in the English literature to date. We conducted a clinicopathologic study of 8 cases of esophageal ectopic sebaceous glands. The median patient age at the time of diagnosis was 60 years (range, 50-71 years), and 7 of the 8 patients were male. A focal lesion was observed in 7 cases, whereas 1 case exhibited multiple lesions throughout the esophagus. Four patients had previously undergone upper gastrointestinal endoscopy; in 3 patients, the focal lesion had not been detected. After diagnosis, 3 cases showed spontaneous regression at least once. Immunohistochemically, sebocytes of all 8 cases were negative for the estrogen receptor (ER) and the progesterone receptor (PgR), whereas sebocytes of 5 cases were positive for the androgen receptor (AR). Basal/parabasal cells were positive for AR, ER, and PgR in 5, 7, and 4 cases, respectively. GATA3 was expressed in the sebocytes and basal/parabasal cells of 6 out of 7 available cases, whereas all of 7 available cases were negative for mammaglobin and GCDFP15. Our report provides the basic clinicopathologic characteristics of esophageal ectopic sebaceous glands by the largest case series reported in English literature to date. Furthermore, the chronological changes, particularly spontaneous regression, and immunohistochemical expression of hormone receptors and GATA3 are compatible with lesions resulting from congenital misplacement under hormonal regulation. Therefore, they seem to be congenital misplacements detectable as a result of hormonal stimulated growth. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is an acquired depigmentation of the skin and the mucous membranes, exhibited as white macules and patches due to selective loss of melanocytes. Etiological theories of vitiligo include genetic, immunological, neurohormonal, cytotoxic, biochemical, oxidative stress, and newer theories of melanocytorrhagy and diminished melanocytes survival. It has been revealed that liver X receptor alpha gene is expressed in skin tissue such as sebaceous glands, hair follicle, keratinocytes, and fibroblasts and is linked to various skin disorders as acne vulgaris and psoriasis. Aim of the Study: To evaluate the association between liver X receptor‐α gene polymorphism (rs11039155 and rs2279238) and vitiligo and whether they are related to disease activity and severity or not. Subjects and Methods: 50 vitiligo patients and 20 age‐ and sex‐matched apparently healthy controls were enrolled. All the included subjects were genotyped using polymerase chain reaction‐restriction fragment length polymorphism analysis technique for (−6G/A) and (+1257C/T) SNPs. Results: Significant statistical difference between cases and controls regarding genotype and allele frequencies for −6G/A polymorphism with predominance of AA genotype (OR: 5.1, 95% CI: 1.6‐15.9) and A allele (OR: 5.3, 95% CI: 1.6‐15.9) in cases and also for +1257C/T polymorphism with predominance of TT genotype OR: 9.2 (95% CI: 1.4‐82.9) and T allele OR: 3.4 (95% CI: 1.4‐8.1) in vitiligo cases. No significant relationship between −6G/A genotypes nor +1257C/T genotypes and disease activity and severity. Conclusion: The study showed significant association between Liver X receptor gene polymorphisms (−6G/A, +1257 C/T) and development of vitiligo in Egyptian patients. However, it failed to show any relation with disease activity nor severity. [ABSTRACT FROM AUTHOR]

Introduction: Combination therapy is widely used for the treatment of acne vulgaris (AV), including local anti-inflammatory drugs containing antimicrobials, such as clindamycin or erythromycin, to inhibit Cutibacterium acnes (C. acnes) growth and at the same time reduce the production of inflammatory mediators. The aim of the study is to compare the antibacterial susceptibility of C. acnes to clindamycin and erythromycin in AV patients compared with healthy patients in the control group (CG). Methods: The prospective study included 56 patients with clinically diagnosed AV symptoms and 12 patients were included in the CG who did not have AV. In the AV group, patient specimen was contents of pustules obtained by squeezing pustules, but in the CG, the specimen was content of sebaceous glands. All specimens were cultivated on a combined Mueller–Hinton solid medium. Identification was done by VITEK2 and followed by determination of antibacterial susceptibility of the isolated C. acnes strains by E-test. Results: C. acnes was isolated from samples of 28 (50%) in the AV group, whereas in the CG, C. acnes was isolated from 10 samples (80%). Resistance to clindamycin in both groups was similar, in 6 (21.4%) samples from patients in the AV group and in 2 (20.0%) samples in the CG, but resistance to erythromycin in the AV patients was higher compared to the CG, in 8 (28.6%) and 1 (10%) accordingly. Conclusion: Patients with AV have higher rates of resistance to erythromycin than the CG, while resistance to clindamycin is comparable. Resistance data showed no statistically significant association between use of erythromycin and clindamycin and the development of resistance. More C. acnes were identified in the CG than in the AV group. [ABSTRACT FROM AUTHOR]

Imaging sebaceous glands and evaluating morphometric parameters are important for diagnosis and treatment of serum problems. In this article, we investigate the feasibility of high‐resolution optical coherence tomography (OCT) in combination with deep learning assisted automatic identification for these purposes. Specifically, with a spatial resolution of 2.3 μm × 6.2 μm (axial × lateral, in air), OCT is capable of clearly differentiating sebaceous gland from other skin structures and resolving the sebocyte layer. In order to achieve efficient and timely imaging analysis, a deep learning approach built upon ResNet18 is developed to automatically classify OCT images (with/without sebaceous gland), with a classification accuracy of 97.9%. Based on the result of automatic identification, we further demonstrate the possibility to measure gland size, sebocyte layer thickness and gland density. [ABSTRACT FROM AUTHOR]

The host-microbiota relationship has evolved to shape mammalian physiology, including immunity, metabolism, and development. Germ-free models are widely used to study microbial effects on host processes such as immunity. Here, we find that both germ-free and T cell-deficient mice exhibit a robust sebum secretion defect persisting across multiple generations despite microbial colonization and T cell repletion. These phenotypes are inherited by progeny conceived during in vitro fertilization using germ-free sperm and eggs, demonstrating that non-genetic information in the gametes is required for microbial-dependent phenotypic transmission. Accordingly, gene expression in early embryos derived from gametes from germ-free or T cell-deficient mice is strikingly and similarly altered. Our findings demonstrate that microbial- and immune-dependent regulation of non-genetic information in the gametes can transmit inherited phenotypes transgenerationally in mice. This mechanism could rapidly generate phenotypic diversity to enhance host adaptation to environmental perturbations. [Display omitted] • Germ-free and T cell-deficient mice show defects in barrier tissue function • Defects persist transgenerationally via non-genetic inheritance • Immune-microbe-influenced inheritance is transmitted by the germlines of both sexes • The microbiome and immune system impact embryonic gene expression of progeny Harris et al. describe phenotypic abnormalities in germ-free and T cell-deficient mice that are not acutely correctable and are non-genetically transmitted to progeny. The parental microbe and immune environment impact gametes to alter early embryonic gene expression, thereby influencing barrier and metabolic tissue of progeny through transgenerational non-genetic inheritance. [ABSTRACT FROM AUTHOR]

Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels. Lens epithelial cells in ARKO mice showed markedly reduced epithelial-to-mesenchymal transition following lens extraction in a surgical model of cataract and posterior capsule opacification. A previously unreported phenotype of preputial sebaceous gland swelling was observed frequently in male ARKO mice homozygous for the mutant AKR1B3 allele. This condition, which was shown to be accompanied by infiltration of proinflammatory CD3+ lymphocytes, was not observed in WT mice or mice heterozygous for the mutant allele. Despite this condition, reproductive fitness of the ARKO strain was indistinguishable from WT mice housed under identical conditions. These studies establish the utility of a new strain of AKR1B3-null mice created to support mechanistic studies of cataract and diabetic eye disease. • AKR1B3-null mice (ARKO) were produced by Crispr-Cas9-mediated gene disruption. • ARKO mice demonstrate reduced EMT response following lens extraction. • ARKO mice are at increased risk for development of preputial gland inflammation. [ABSTRACT FROM AUTHOR]

Our patient has had AA since 3 years, but he recently developed age-related hormone-induced seborrhea on the background of fully functional sebaceous glands over the scalp. Sir, Alopecia areata (AA) is a common cause of non-scarring hair loss. On examination, numerous closely set open comedones with regrowing and vellus hair were seen all over the scalp [Figure 1]. [Extracted from the article]

Hair follicle (HF) morphogenesis and cycling are a result of intricate autonomous epithelial-mesenchymal interactions. Once the first HF cycle is complete it repeatedly undergoes cyclic transformations. Heparan sulfate (HS) proteoglycans are found on the cell surface and in the extracellular matrix where they influence a variety of biological processes by interacting with physiologically important proteins, such as growth factors. Inhibition of heparanase (an HS endoglycosidase) in in vitro cultured HFs has been shown to induce a catagen-like process. Therefore, this study aimed to elucidate the precise role of HS in HF morphogenesis and cycling. An inducible tetratransgenic mouse model was generated to excise exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells from P21. Interestingly, EXT1(StEpiΔ/StEpiΔ) mice presented solely anagen HFs. Moreover, waxing the fur to synchronize the HFs revealed accelerated hair regrowth in the EXT1(StEpiΔ/StEpiΔ) mice and hindered cycling into catagen. The ablation of HS in the interfollicular epidermal cells of mature skin led to the spontaneous formation of new HFs and an increase in Sonic Hedgehog expression resembling wild-type mice at P0, thereby indicating that the HS/Sonic Hedgehog signaling pathway regulates HF formation during embryogenesis and prevents HF formation in mature skin. Finally, the knock-out of HS also led to the morphogenesis and hyperplasia of sebaceous glands and sweat glands in mature mice, leading to exacerbated sebum production and accumulation on the skin surface. Therefore, our findings clearly show that an intricate control of HS levels is required for HF, sebaceous gland, and sweat gland morphogenesis and HF cycling.

Objective. To study the clinical characteristics and surgical outcomes of anti-NMDAR encephalitis and the immunopathology of associated teratomas. Methods. Twenty-one patients were enrolled in this retrospective study, who were diagnosed with anti-NMDAR encephalitis with ovarian teratoma and admitted to two tertiary hospitals in South China from July 2014 to December 2019. The clinical data of patients were reviewed. Comparisons were made between the patients with different outcomes after surgery. Immunohistochemical analyses of associated ovarian teratomas were performed. Results. The mean age of the patients was 24.33 ± 5.12 years. The peak seasons of disease onset were autumn and winter (30.61% and 32.65%). The symptoms could be divided into 8 categories, including psychiatric abnormalities, seizures, movement dysfunction, consciousness disorders, autonomic dysregulation, speech disturbance, central hypoventilation, and memory deficits. All patients developed four or more categories of symptoms within the first four weeks. Twelve patients (57.1%) had a maximum mRS of 5, and 11 patients (52.4%) were admitted to ICU. Twenty patients received surgery, and only 3 patients were diagnosed pathologically with immature ovarian teratomas, while the other 17 patients had mature ovarian teratomas. After surgery, 17 patients (85.0%) got clinical improvement. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. Immunohistochemical analysis revealed that there were NMDAR-positive neural tissues in all 8 teratomas and in which 3 cases also contained large numbers of NMDAR-positive sebaceous glands and squamous epithelial tissues. Conclusion. The disease is of high prevalence in autumn and winter. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. NMDAR-positive neural tissue is not the only etiological factor of encephalitis. We speculate that encephalitis development in some patients may result from NMDAR expression in sebaceous glands and squamous epithelial tissues. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) is an anticancer treatment that utilizes the interaction of light and a photosensitiser (PS), promoting tumour cell death mediated by generation of reactive oxygen species. In this study, we evaluated the in vitro photoactivity of four meso-substituted porphyrins and a porphyrin coupled to a fullerene.Methods: The cell line employed was the LM3 mammary adenocarcinoma, and the PS with the best photokilling activity was administered to mice bearing the LM3 subcutaneously implanted adenocarcinoma. The TEMCP4+ porphyrin and its analogue TEMCC4+ chlorine contain four identical carbazoyl substituents at the meso positions of the tetrapyrrolic macrocycle and have A4 symmetry. The TAPP derivative also has A4 symmetry, and it is substituted at the meso positions by aminopropoxy groups. The DAPP molecule has ABAB symmetry with aminopropoxy and the trifluoromethyl substituents in trans positions. The TCP-C604+ dyad is formed by a porphyrin unit covalently attached to the fullerene C60.Results: The PSs are taken up by the cells with the following efficiency: TAPP> TEMCP4+ = TEMCC4+ > DAPP >TCP-C604+, and the amount of intracellular PS correlates fairly with the photodamage degree, but also the quantum yields of singlet oxygen influence the PDT outcome. TAPP, DAPP, TEMCC4+ and TEMCP4+ exhibit high photoactivity against LM3 mammary carcinoma cells, being TAPP the most active. After topical application of TAPP on the skin of mice bearing LM3 tumours, the molecule is localized mainly in the stratum corneum, and at a lower extent in hair follicles and sebaceous glands. Systemic administration of TAPP produces a tumour: normal skin ratio of 31.4, and high accumulation in intestine and lung.Conclusion: The results suggest a potential use of topical TAPP for the treatment of actinic keratosis and skin adnexal neoplasms. In addition, selectivity for tumour tissue after systemic administration highlights the selectivity of and potentiality of TAPP as a new PS. [ABSTRACT FROM AUTHOR]

Acne is a common, chronic, inflammatory disease of the pilosebaceous unit. It has a significant impact on patient quality of life, especially when lesions occur on cosmetically sensitive areas. Chemical peeling is a well-known option in the treatment of acne vulgaris, but little is known about azelaic acid (AZA) peels. To determine the efficacy of 30% AZA peel, in decreasing the amount of secreted sebum, and reducing acne lesions. The study involved 35 women, with acne lesions on face skin. All the subjects underwent a series of six treatments, performed every 2 weeks. A series of treatments contributed to a statistically significant reduction in the amount of secreted sebum. Similarly, highly significant values determining the overall number of acne lesions and the severity of the disease according to the IGA scale were also changed. The procedure was well tolerated by all participants. Peels with 30% AZA reduced acne lesions and normalized the activity of the sebaceous glands. The reduction of sebum allows us to believe that obtained good results in patients will be stable and long-lasting. [ABSTRACT FROM AUTHOR]

[Display omitted] The dermal papilla (DP) represents the major regulatory entity within the hair follicle (HF), inducing hair formation and growth through reciprocal interactions with epithelial cells. However, human DP cells rapidly lose their hair inductive ability when cultured in an epithelium-deficient environment. To determine if the conditioned medium collected from interfollicular keratinocytes (KCs-CM) is capable of improving DP cell native properties and inductive phenotype. DP cells were cultured with KCs-CM both in 2D and 3D culture conditions (spheroids). Further, the hair-inductive capacity of DP cells precultured with KCs-CM was tested in a hair reconstitution assay, after co-grafting with human keratinocytes in nude mice. We demonstrate that KCs-CM contributes to restore the inductivity of cultured human DP cells in a more effective mode than the conventional 3D-cultures. This is supported by the higher active alkaline phosphatase (ALP) levels in DP cells, the improved self-aggregative capacity and the reduced expression of α-SMA and the V1-isoform of versican. Moreover, DP cells cultured with KCs-CM displayed a secretome profile (VEGF, BMP2, TGF- β1, IL-6) that matches the one observed during anagen. KCs-CM also enhanced DP cell proliferation, while preventing cells to undergo morphological changes characteristic of high passage cells. In opposition, the amount of collagenous and non-collagenous proteins deposited by DP cells was lower in the presence of KCs-CM. The improvement in ALP activity was maintained in 3D spheroidal cultures, even after KCs-CM retrieval, being superior to the effect of the gold-standard culture conditions. Moreover, DP cells cultured with KCs-CM and grafted with human keratinocytes supported the formation of HF- and sebaceous gland-like structures in mice. The proposed strategy encourages future cell-based strategies for HF regeneration not only in the context of hair-associated disorders, but also in the management of wounds to aid in restoring critical skin regulatory appendages. [ABSTRACT FROM AUTHOR]

Background: Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors. Methods: We performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese. Results: Systematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found that TNF rs1800629 A allele carriers and CYP17A1 rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33–0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40–0.79), respectively, across populations. Overall, FST (follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neither TIMP2 (TIMP metallopeptidase inhibitor 2) rs8179090 nor CYP1A1 rs4646903 (pOR: 0.96, 95% CI: 0.80–1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3′ UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation. Conclusions: This systematic review and meta-analysis suggest that genes influencing inflammatory responses, specifically TNF, and genes influencing the function and activity of sebaceous glands, specifically CYP17A1 and FST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments. [ABSTRACT FROM AUTHOR]

Acne is a multifactorial disease with endocrine influences. The objective of this paper is to present the pathophysiological bases of acne and its interactions with the endocrine system. The importance of traditionally described hormones such as testosterone, dihydrotestosterone and insulin as trophic stimuli for the sebaceous gland are reviewed. This paper also explores the influence of other hormones traditionally less associated with acne such as cortisol, proopiomelanocortin, prolactin and growth hormone, that have proven to influence sebum secretion by the pilosebaceous unit. Finally, the interaction of these pathophysiological phenomena is described in entities such as polycystic ovary syndrome, congenital adrenal hyperplasia and Cushing syndrome. [ABSTRACT FROM AUTHOR]

Introduction. Previously considered an exceedingly rare entity, sebaceous carcinoma of the breast is now regarded in the World Health Organization 2019 classification as a "special histopathological pattern" of invasive breast carcinoma of no special type. Case Description. In this article, we report the case of a fine needle aspiration cytology and the histopathological features of a breast carcinoma with clear-cut morphological features suggesting sebaceous differentiation, but showing no positive staining with the anti-adipophilin antibody. Conclusions. A morphologically clear-cut sebaceous differentiation is not invariably associated with adipophilin positivity; moreover, in breast carcinoma, adipophilin positivity does not automatically imply sebaceous differentiation. At present, immunomorphological evidence for the recognition of sebaceous carcinoma as a "special type" breast carcinoma subtype is too weak. [ABSTRACT FROM AUTHOR]

Sebaceous glands (SGs), typically associated with hair follicles, are critical for the homeostasis and function of mammalian skin. The main physiological function of SGs is the production and holocrine secretion of sebum to lubricate and protect the skin. Defective SGs have been linked to a variety of skin disorders, including acne, seborrheic dermatitis and formation of sebaceous tumors. Thus, a better understanding how SGs are formed and maintained is important to unravel the underlying molecular and cellular mechanisms of SG pathologies and to find better and effective therapies. Over the last two decades, research has come a long way from the initial identification of skin epithelial stem cells to the isolation and functional characterization of multiple stem cell pools as well as a better understanding of their unique and complex activities that drive skin homeostasis and operate in skin pathologies. Here, we discuss recent progress in unravelling cellular mechanisms underlying SG development, homeostasis and sebaceous tumor formation and assess the role of stem and progenitor cells in controlling SG physiology and disease processes. The development of elegant in vivo imaging as well as various in vitro and ex vivo stem cell and SG tissue models will advance mechanistic studies on SG function and allow drug screening and testing for efficient and successful targeting SG pathologies. [ABSTRACT FROM AUTHOR]

The emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E‐cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris is a multifactorial disease affects the pilosebaceous follicle and results in inflammatory and non-inflammatory lesions with certain role of cytokines in its pathogenesis. Interleukin-35 (IL- 35) cytokine has been shown to exhibit immunosuppressive activities, which are distinct from other members of IL-12 family. IL-35 is also unique in that it is expressed primarily by regulatory T- cells (Tregs) rather than by antigen-presenting cells (APCs). Objective: To investigate the role of IL-35 in the pathogenesis of acne vulgaris by assessing its levels in lesional skin and serum of patients with acne vulgaris compared with normal individuals. Patients and methods: 44 subjects were divided into 2 groups: Group 1: It included measurement of serum and tissue level of interleukin 35 in 22 acne vulgaris patients with age group (15-30). All of them were subjected to detailed history taking, dermatological and general examination. Group 2: It included 22 healthy, age, and gender matched individuals as a control group. Result: Our results show a highly statistically significant difference between acne patient and control regarding IL-35 level in serum and tissue. Conclusion: Our study may provide evidence that serum and tissue IL-35 are important anti-inflammatory cytokines. They are actively expressed by the sebaceous glands. They have significant higher expression in acne patients. They are hypothesized to play a key role in acne cure at multiple points, through their anti-inflammatory action. This effect may be hindered in acne vulgaris by undiscovered obstacles. [ABSTRACT FROM AUTHOR]

Objectives: Transverse sectioning of skin biopsy specimens has revolutionised assessment of human alopecia by demonstration of every hair in each specimen, allowing quantitative evaluation of follicular activity. Since only vertical sectioning is performed routinely in veterinary laboratories, we aimed to determine whether transverse sectioning was a valuable technique in assessment of canine alopecia. Methods: Paired vertical and transverse sections of biopsy specimens from 31 alopecic dogs were examined independently in triplicate in random order and blinded to previous diagnosis using a standard check‐list proforma. Assessments of key features (follicular activity [anagen/telogen], infundibular hyperkeratosis, sebaceous gland abnormalities, pigment clumping, dermal inflammation) by each sectioning method were compared. Results: In the 31 cases, (atrophic [n = 13], dysplastic [n = 12], inflammatory diseases [n = 6]), follicular inactivity scores (median, [lower‐upper quartile]) in transverse sections significantly exceeded those in vertical sections (transverse 4 [3‐5], vertical 3 [2‐4]). Agreement between the two sectioning planes was moderate for infundibular hyperkeratosis (kappa = 0.5210) and dermal inflammation (0.4351), fair for sebaceous gland abnormalities (0.3966) and pigment clumping (0.2197), but slight for follicular activity (0.1041). Vertical sectioning demonstrated diagnostically important epidermal pathology (n = 2) and dermal thinning (n = 3) whereas transverse sectioning enhanced assessment of hair growth phase (n = 11), follicular structure and architecture (n = 11), and focal luminal or mural folliculitides (n = 3). Clinical significance: Transverse sectioning confers significant benefits and complements traditional vertical sectioning in the histological assessment of canine hair follicle diseases, particularly when subtle abnormalities comprise distorted compound follicle architecture, hair cycle arrest or when relatively few adnexal structures are affected. [ABSTRACT FROM AUTHOR]

This study was conducted on skin samples from New Zealand white rabbits during the period E15 days prenatal to E25. to investigate the histomorphological development of the skin, hair follicle, Sebaceous glands. Early in the fetal life (E15) the epidermis is in the form of simple squamous epithelium or stratified Nonkeratinized squamous epithelium of two or more layers, depending on the region studied, while the dermis is in the form of loose connective tissue composed of mesenchymal cells in a loose and irregular shape. (E20) prenatal, the epidermis is stratified squamous epithelium non-keratinized composed of more than three layers including the periderm, the intermediate layer and the basal layer in all regions, except Fingered hand and foot that appearance keratinized squamous. the cells of the mesoderm begin to condense under the basal layer, indicating the beginning of the formation of hairs placodes. Stratification became evident in(E25) of prenatal with a marked keratinized and extension of hair follicles in the dermis, accompanied by the beginning of the development of sebaceous glands in the form of a group of cells. During our study of the development of the skin of the New Zealand rabbit before birth, we could not notice any sweat glands in the examined skin samples. [ABSTRACT FROM AUTHOR]

Sebaceous glands are sebum‐secreting components of pilosebaceous units. In the second of this two‐part series, we review the pathologies in which sebaceous glands are primarily and secondarily implicated. They are primarily involved in steatocystoma simplex and multiplex, sebaceous gland hyperplasia, sebaceoma, sebaceous adenoma, sebaceous carcinoma, nevus sebaceus, and folliculosebaceous cystic hamartoma. Sebaceous glands are secondarily involved in acne vulgaris, seborrheic dermatitis, and androgenic alopecia. Steatocystoma multiplex is a benign congenital anomaly presenting as yellow cysts primarily on the upper body. Sebaceous gland hyperplasia is characterized by yellow, telangiectatic papules with a central dell, and it can be treated with topical retinoids or surgical excision. Sebaceoma clinically presents on the head and neck region as a skin‐colored nodule and can be distinguished by immunohistochemistry. Stains used in the diagnosis of sebaceous adenoma and carcinoma include epithelial membrane antigen and adipophilin immunoperoxidase. Surgical excision is the preferred treatment for sebaceoma, sebaceous adenoma, and sebaceous carcinoma. Excision is not always indicated for nevus sebaceus. Folliculosebaceous cystic hamartoma is a relatively rare condition exhibiting both epithelial and mesenchymal components. Patients with acne vulgaris commonly present with papules of closed and open comedones displaying hypercornification. Seborrheic dermatitis presents as sharply demarcated yellow or red patches or plaques; antifungal agents, corticosteroids, and combination antifungal/anti‐inflammatory therapies are common treatment modalities. As a result of hair follicle miniaturization, females with androgenic alopecia present with diffuse hair thinning, while men tend to present with balding and hairline recession. [ABSTRACT FROM AUTHOR]