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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.

Necrotizing infundibular crystalline folliculitis is a rare entity, which is a distinctive clinical and histopathological entity. Eruptive yellow waxy umbilicated folliculocentric plugs clinically correspond to pale crystalline filaments embedded in an amorphous sebum-rich material. Remarkably, only the superficial infundibular ostia remain, and the distended cavity is devoid of a follicular or sebaceous gland remnant. The pathogenesis of this enigmatic event remains to be established. The emergence of necrotizing infundibular crystalline folliculitis (NICF) as a paradoxical side effect of antitumor inhibitors epidermal growth factor receptor vascular endothelial growth factor and more recently programmed death-1 represents the expression of altered molecular pathways that underpin the pathogenesis of NICF. To explore these pathways, it is necessary to explore the hierarchy of follicular stem cells, particularly the potential role of committed infundibular stem cells that play a key role in wound healing. Committed infundibular stem cells are closely linked to the sebaceous gland stem cell axis, and this has relevance in the process of homeostatic repair of sebaceous follicles in the wake of folliculitis. The unscheduled modulation of this infundibular homeostatic sebaceous repair axis by epidermal growth factor receptor vascular endothelial growth factor, and programmed death-1 may lead to an aberrant outcome with metaplasia of infundibular keratinocytes to sebocytes. In the absence of sebaceous gland differentiation, these metaplastic infundibular sebocyte cells would lead to the consumption and loss of the infundibulum as a result of holocrine sebum production. This conceptual pathogenic pathway for NICF is constructed by incorporating recent advances in the fields of follicular stem cells, wound repair, follicular homeostasis, regulatory T cells, and molecular pathways linked to the biologicals inducing NICF.

Preputial glands are large lipid and hormone secreting sebaceous organs of mice, and present a convenient model for the investigation of biological processes in sebocytes. Suppression of ATG7-dependent macroautophagy/autophagy in epithelial cells of murine skin causes enlargement of hair follicle-associated sebaceous glands and alters the lipid profile of sebum. We have now extended these studies to the preputial glands and find that autophagy significantly delays the onset of age-related ductal ectasia, influences lipid droplet morphology and contributes to the complete dissolution of the mature sebocytes during holocrine secretion. Single cell RNA sequencing showed that many genes involved in lipid metabolism and oxidative stress response were downregulated in immature and mature epithelial cells of ATG7-deficient glands. When analyzing the lipid composition of control and mutant glands, we found that levels of all phospholipid classes, except choline plasmalogen, were decreased in the mutant glands, with a concomitant accumulation of diacyl glycerides. Mass spectrometric imaging (MSI) demonstrated that phospholipid species, specifically the dominant phosphatidylcholine (PC 34:1), were decreased in immature and mature sebocytes. In addition, we found a strong reduction in the amounts of the pheromone, palmityl acetate. Thus, autophagy in the preputial gland is not only important for homeostasis of the gland as a whole and an orderly breakdown of cells during holocrine secretion, but also regulates phospholipid and fatty acid metabolism, as well as pheromone production. ABBREVIATIONS: ATG7: autophagy related 7; BODIPY: boron dipyrromethene; DAG: diacyl glycerides; DBI: diazepam binding inhibitor; GFP: green fluorescent protein; KRT14: keratin 14; HPLC-MS: high performance liquid chromatography-mass spectrometry; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MSI: mass spectrometric imaging; ORO: Oil Red O; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PG: preputial gland; PLIN2: perilipin 2; PtdIns: phosphatidylinositol; PL: phospholipids; POPC: 1-palmitoyl-2-oleoyl-PC; PS: phosphatidylserine; qRT-PCR: quantitative reverse transcribed PCR; SG: sebaceous gland; scRNAseq: single-cell RNA sequencing; TAG: triacylglycerides; TLC: thin layer chromatography.

This study aimed at reviewing the importance of medicinal plants for the treatment of common hair problems such as baldness, alopecis hair fall, gray hair, dryness and most comman drandruff. The various herbal ingredient are used in the formation are Aloe, Amla, Curry leaves, Camphore, Coconut oil, Eclipta alba, Hibiscus, Heena, Neem, Fenugreek, Sage, Apamarg, Onion, grape seeds, Jatamanshi, Rosamary, Thyme, Tulsi, Garlic and Neem. All ingredients provide essential nutrients such as Vitamin, terpenoids and many essential oils to maintain normal function of sebaceous gland and overall care of skin and hair. Keywords: Hair disease, Medicinal plants, Hair oil

Demodex folliculorum and brevis are commensal mites that live in low densities in human pilosebaceous follicles as part of the normal adult microbiota, but that give rise to demodicosis and, possibly, rosacea, when they proliferate excessively. This proliferation is favored by various factors, including age, marked immunosuppression, sebaceous gland hyperplasia, and hypervascularization-related factors. To study possible factors influencing mite proliferation, we explored the effects of different variables on Demodex densities (Dd) in a retrospective study of two groups of subjects selected on the basis of their clinical diagnosis: Demodex+, consisting of subjects with demodicosis or with centro-facial papulopustules suggesting rosacea (n = 844, mean Dd 263.5 ± 8.9 D/cm2 ), and Demodex-, consisting of subjects with other facial dermatoses or healthy facial skin (n = 200, mean Dd 2.3 ± 0.4 D/cm2 ). Demodex densities were measured using two consecutive standardized skin surface biopsies (SSSB1 [superficial] and SSSB2 [deep]) taken from the same facial site on each subject. In the Demodex+ group: the SSSB1 decreased with age in women (p = 0.004), and the SSSB2 increased with age in men (p = 0.001) (the pattern was similar for SSSB1 + 2, but not statistically significant); Dds were lower in those who had received cortisone (either topically or systemically); 13 subjects (1.5%) had known immunosuppression, 62 (7.3%) had hypothyroidism, and in 20 (3.6% of the women) there was a reported link with pregnancy; 78 of the subjects (9.2%) were part of a pair from the same family or household; when associated bacterial infection was suspected, Staphylococcus epidermidis was often isolated. Our results suggest close interactions between the mite, sebaceous gland size and function, and subtle variations of immune status. Potential factors influencing Demodex proliferation should be further investigated, including hypothyroidism, pregnancy, corticosteroid administration, Staphylococcus epidermidis, contagiousity, and genetic background.

The pilosebaceous unit is a sebaceous gland with hair follicles. One of the hormones that affects the pilosebaceous unit is androgen, a steroid hormone that plays an important role in the expression of the phenotype of men and women. Androgen consist of testosterone and dihydrotestosterone which are activated by androgen receptors. Androgen in the pilosebaceous unit affect sebum production and hair growth. Androgen receptors in the sebaceous glands are found on sebocytes and in hair follicles in the dermal papillae of hair follicles

Pathogenic variants inTP53have been classically thought to cause Li-Fraumeni syndrome (LFS), a cancer predisposition with high risks for various childhood- and adult-onset malignancies. However, increased genetic testing has lately revealed, that pathogenic variant carriers exhibit a broader range of phenotypes and that penetrance may be dependent both on variant type and modifiers. Using next generation sequencing and short tandem repeat analysis, we identified germline pathogenic variants inTP53andRAD51Clocated incison chromosome 17 in a 43-year-old male, who has developed a rare sebaceous gland carcinoma (SGC) but so far no tumors of the LFS spectrum. This course mirrors aTrp53-Rad51c-double-mutantcismouse-model, which similarly develops SGC, while the characteristicTrp53-associated tumor spectrum occurs with significantly lower frequency. Therefore, we propose that co-occurent pathogenic variants inRAD51CandTP53may predispose to SGC, reminiscent of Muir-Torre syndrome. Further, this report supports the diversity of clinical presentations associated with germlineTP53alterations, and thus, the proposed expansion of LFS to heritableTP53-related cancer syndrome.

The present investigation aims to describe the morphometric and histological features of the skin in the desert hedgehog (Paraechinus aethiopicus). Skin biopsies were harvested from the dorsal, abdominal, labial, and nasal regions to monitor the structural differences. Histologically, the skin followed the general mammalian architectural pattern and was composed of three main layers; epidermis, dermis, and hypodermis. However, there were some species-specific differences. The hairless skin of the rhinarium was the thickest and no sebaceous gland was detected. Moreover, the lateral nasal glands were recorded for the first time in hedgehogs. This feature is very common in mammals that utilize thermal panting strategy rather than sweating in thermoregulation. The histological analysis of the dorsal and ventral skin confirmed our observation, as no sweat gland was detected. The labial glands were overpopulated in the skinny surface of the upper lip, while the vermillion border devoid glands at all. Hedgehog’s hair exhibited morphological and structural modifications. The dorsal skin exhibited stiff spines, while the belly skin was covered by dense fur. The vibrissal hairs were located on the snout and regularly arranged on both sides of the labial skin, embedded in the blood sinus system and enveloped within a dense collagenous capsule. Together, these data suggest that the desert hedgehog has a unique integumentary system enabling him to accommodate the extreme environmental conditions of the desert habitat.

Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

Uncoupling protein 1 (UCP-1) was believed to be an exclusive protein found in the brown adipose tissue of small rodents and humans; however, recent studies show that the expression of UCP-1 protein has been found in the sebaceous glands of the mouse tail and human skin. There are a few reports about the presence of UCP-1 in the sebaceous glands of other rodents, such as the Sunda porcupine (Hystrix javanica), a wild spiny rodent commonly found in Indonesia with a large sebaceous gland. The aim of this study was to identify the presence of UCP-1 in the sebaceous glands on the skin of the Sunda porcupine. The skin from three regions (thoracodorsal, lumbosacral and apex caudal) of eight adult Sunda porcupines was used to detect UCP-1-immunopositive cells through immunohistochemistry. All three regions were found immunopositive to anti-UCP-1 antibody in the sebaceous gland of quill and hair follicles, and the epidermal layer in quill and hair follicles with various intensities. The result of immunohistochemistry revealed that the thoracodorsal and apex caudal region was the most intense immunoreaction followed by the lumbosacral region. These findings proved that the presence of UCP-1 was also identified in the sebaceous glands of other rodent (Hystrix javanica) and regions of the body, which has not been reported previously.

Little is known about the pathological roles of sebaceous glands in canine skin diseases, as most examinations have been conducted with cultured human sebaceous epithelial cell lines. To our knowledge, there is no available canine sebaceous epithelial cell line. The purpose of this study was to establish a canine sebaceous epithelial cell line and characterize it. An eyelid mass in a dog was surgically resected for treatment, and it was histologically diagnosed as sebaceous epithelioma. Collected tissue was conducted for culture, and the growing epithelial-like cells were passaged. The cells showed continuous proliferation for over 6 months. After 40 passages, the cells were named CMG-1. Lipid droplets in the cytoplasm of CMG-1 cells were confirmed by Oil Red O staining. As reported in studies with human sebaceous epithelial cell lines, lipogenesis in CMG-1 cells was promoted by linoleic acid, whereas transforming growth factor-β (TGF-β) suppressed it. Additionally, real-time PCR revealed that the expression levels of chemokines and cytokines, including CC chemokine ligand (CCL)-2, CCL-20, CXCL-10, Tumor necrosis factor-α (TNF-α), Interleukin (IL)-1α, IL-1β, and IL-8, were significantly increased in CMG-1 cells following treatment with lipopolysaccharide. In conclusion, we successfully established a new canine sebaceous epithelial cell line. Our data indicated that lipogenesis and inflammatory responses were quantitatively evaluable in this cell line. CMG-1 cells could be useful for the pathological analysis of sebaceous gland diseases in dogs.

Abnormal hair loss results from a variety of factors, such as metabolic dysfunctions, immunodeficiency, and environmental stressors. Here, we report that mutant mice having defects in liver function, develop alopecia. We have shown previously that in mice lacking a Cnot3 gene, which encodes an essential component of the CCR4-NOT deadenylase complex in liver (Cnot3-LKO mice), the liver does not mature properly, resulting in various pathologies such as hepatitis, hepatic necrosis, and anemia. Unexpectedly, Cnot3-LKO mice start to lose hair around postnatal day 17 (P17). The region of hair loss expands all across their backs and symptoms persist until around P28-30. Afterward, hair re-grows, and Cnot3-LKO mice show complete hair recovery by P40. The phenotype is dependent on mouse genotype, indicating that hair follicle morphogenesis and cycling are influenced by abnormal liver development. By performing histological, quantitative PCR, and immunoblot analyses, we detected sebaceous gland (SG) hypertrophy accompanied by an increase of peroxisome proliferator-activated receptor gamma (PPARgamma). Collectively, these findings suggest that paracrine signaling related to liver function influences hair growth, at least in part, by altering lipid metabolism.

Background: Hair follicle and sebaceous gland inflammation causes acne, which is a long-term, chronic skin condition. The androgen-induced sebum overproduction leads to first acne appearance. It is caused by altered and aberrant keratinization, inflammation and the colonization of facial hair follicles by the bacteria Propionibacterium acnes. Acne also has a delayed immune response, as well as influences from the environment and genetics. Treatments for post-acne scarring have included topical preparations such as chemical peels, dermabrasion, laser resurfacing and punch excision and punch elevation, as well as fat transfer, implantation of autologous collagen and cultured and expanded autologous fibroblasts. Other treatments have included trichloroacetic acid focal treatment and skin microneedling to improve the dermal extracellular matrix (ECM) proteins. Objective: To determine the updated treatment modalities in atrophic post-acne scars. Conclusion: In most types of atrophic acne scars combination therapies typically provide superior outcomes than solo treatments.

Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here, we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Colonization of germ-free mice was insufficient to trigger increased SPRR expression in mouse skin, but LPS injected into mouse skin stimulated increased expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through activation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa, and skin commensals. Thus, Sprr1a−/−;Sprr2a−/− mice are more susceptible to MRSA and P. aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.

Demodex folliculitis is a condition caused by inflammation of the pilosebaceous unit due to the Demodex folliculorum mite.1 The mite is a normal inhabitant of the human hair follicle and though they have been found in all areas of human skin, they predominate on the face. The face, with a high density of active sebaceous glands is a desirable home for demodex mites who feed on exfoliated epidermal cells and sebaceous gland secretions. The eruption of demodex folliculitis can mimic many common skin pathologies such as rosacea, acne vulgaris, and bacterial folliculitis.2 When demodex folliculitis occurs with immunocompromised patients, the clinical presentation can be atypical and severe.3 Herein, we report a case of severe demodex folliculitis and review of the literature.

The aim of the present study was to develop and characterize karanjin-loaded ethosomes-based gel formulation for enhanced topical delivery and effective therapy of skin acne. Karanjin-loaded ethosomes (K-ETH) presented a nanometric size of 140.87 ± 2.35 nm, entrapment of 71.41 ± 2.74% and enhanced permeation with 1.9 times increase in the flux and 2.4 times higher skin deposition compared to the hydro-ethanolic solution of karanjin. The DSC analysis confirmed successful entrapment of the karanjin within the ethosomes. The developed ethosomes were incorporated in the carbopol gel for adequate application on the skin surface. The ethosomal gel (K-EGF) also exhibited greater penetration in the rat skin as revealed by CLSM. The optimized K-EGF formulation was non-irritant to the skin as evident by Draize score test and histopathological examination. The highest zone of inhibition, 30.0 ± 1.52 mm and 36.22 ± 0.57 mm was produced by the K-EGF against Propionibacterium acnes and Staphylococcus epidermidis, respectively, indicating substantial antibacterial properties of the K-EGF. DPPH assay indicated its potent antioxidant effects. Substantial anti-inflammatory effects in the carrageenan-induced edema in the rat paw were evident with inhibition of rat paw edema by 66.66% and 70.37% upon application of K-EGF and standard anti-inflammatory agent, respectively. Anti-acne effects were also evident with K-EGF treatment with significant decrease in number and size of sebaceous gland units in dermis. Overall, the above findings vouch for a therapeutic opportunity to improve topical delivery of karanjin in acne treatment employing ethosomal gels as the promising carrier system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02978-3.

Sebaceous glands are adnexal structures, which critically contribute to skin homeostasis and the establishment of a functional epidermal barrier. Sebocytes, the main cell population found within the sebaceous glands, are highly specialized lipid-producing cells. Sebaceous gland-resembling tissue structures are also found in male rodents in the form of preputial glands. Similar to sebaceous glands, they are composed of lipid-specialized sebocytes. Due to a lack of adequate organ culture models for skin sebaceous glands and the fact that preputial glands are much larger and easier to handle, previous studies used preputial glands as a model for skin sebaceous glands. Here, we compared both types of sebocytes, using a single-cell RNA sequencing approach, to unravel potential similarities and differences between the two sebocyte populations. In spite of common gene expression patterns due to general lipid-producing properties, we found significant differences in the expression levels of genes encoding enzymes involved in the biogenesis of specialized lipid classes. Specifically, genes critically involved in the mevalonate pathway, including squalene synthase, as well as the sphingolipid salvage pathway, such as ceramide synthase, (acid) sphingomyelinase or acid and alkaline ceramidases, were significantly less expressed by preputial gland sebocytes. Together, our data revealed tissue-specific sebocyte populations, indicating major developmental, functional as well as biosynthetic differences between both glands. The use of preputial glands as a surrogate model to study skin sebaceous glands is therefore limited, and major differences between both glands need to be carefully considered before planning an experiment.

A male Holstein-Friesian calf was born with multiple, cauliflower-like, pale pink cutaneous masses on the head and limbs. On histopathological examination, the cutaneous masses were diagnosed as congenital cutaneous fibropapillomatosis. Those lesions involved focal proliferation of sebaceous gland in the dermis. There were no histological findings to suggest bovine papillomavirus infection, such as the presence of intranuclear inclusion bodies, large keratohyalin granules, and koilocytosis. Furthermore, papillomaviral antigens and DNA were not detected by immunohistochemistry and polymerase chain reaction, respectively. These results suggested that there was no association between these cutaneous lesions and bovine papillomavirus infection, and the lesions were considered as harmartomatous changes.

Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.

Introduction : Acne vulgaris (AV) is a chronic inflammatory disorder of pilosebaceous follicle with polymorphic dermatological manifestation such as comedones, papules, pustules, nodules, and scar. Acne vulgaris can be categorized into three degrees of severity based on lesions count: mild, moderate, and severe. There are four factors in the pathogenesis of AV: pilosebaceous follicle hyperproliferation, excessive sebum production, inflammation, and presence of Propionibacterium acnes. The degree of severity is mainly related to the number of an individual's sebaceous gland. Individuals with AV usually have large sebaceous glands that are very active, large pores, and oily skin. Objectives : To describe prevalence and severity of acne vulgaris in students of mechanical engineering major in faculty of engineering Diponegoro University batch 2018. Methods : This is an observational study with cross sectional approach in which author describes prevalence of AV and its degree of severity in students of mechanical engineering major in faculty of engineering diponegoro university batch 2018. Subjetcs were obtained from simple random sampling. There were 71 eligible subjects meeting inclusion criterias. Dermatovenereology residents performed physical examination on subjects to determine whether or not the subject had. Subjects with AV were classified into "positive" group, otherwise "negative". Subjects were obtained with simple random sampling technique. All subjects (100%) had acne vulgaris. Severity of AV varies with 38% subjects had mild AV, 59.2% had moderate AV and 2.8% had severe AV. Conclusions : All subjects (100%) had AV, mostly of moderate severity. Keywords : Acne Vulgaris; prevalence; severity

Acne vulgaris is a type of chronic disease of the skin which is mainly caused by the blockage in the sebaceous gland or having any inflammation in those glands which is together is known as pilosebaceous units. It mainly affects the areas having the highest number of sebaceous follicles; those are the face, the back and upper region of the chest. It is a disease that mainly affects the adolescent age group but can be found in any age group. These are present as inflammatory pustules, papules, cysts and nodules, non-inflammatory closed comedones (whiteheads), ripen comedones (blackheads), or a mixture of lesions. Acne is most commonly seen in almost every human being at some point in their lives. There are 20-25 chances of progression of acne to the severe case which leads to permanent scarring. These complications lead to psychological problems like depression, social isolation, lowered self-esteem, and lowered self-confidence. The aim of treating acne is to prevent severe and long-term complications. The present review focuses on novel drug delivery systems for the treatment of acne. It also includes conventional treatments currently available in the market, its limitation and different strategies to overcome these limitations.

Background: Acne vulgaris is a multifactorial disease, studies have focused on the role of oxidative stress in the aetiopathogenesis of acne . Malondialdehyde (MDA) is a good marker of oxidative stress. Intense pulsed Light (IPL) systems are used in treatment of acne, the mechanism is reduction of Propionibacterium acnes (P. acnes) levels, decrease in the sebaceous gland function. Objective: The study objective was to estimate the efficacy of IPL on levels of oxidative stress in acne patients taking MDA levels as an indicator before and after IPL. Subjects and methods: an interventional study carried out on 20 patients with acne and 20 individuals free of acne. The severity of acne was assessed using the Global Evaluation Acne (GEA) scale. The levels of MDA were measured before the first IPL session and after 2 weeks from the last session using a spectrophotometer. Each patient received 3 IPL sessions biweekly. MDA levels in the acne free group was measured and compared to that of cases. Results: MDA levels showed a statistically significant difference among patient after IPL treatment compared to levels before IPL treatment with the lower levels in after IPL treatment. MDA levels showed a statistically significant difference between patients and acne free individuals, with MDA being higher in patients, indicating a condition of oxidative stress that had resulted from a high level of lipid peroxidation in acne patients. As regard MDA levels, patients with moderate acne showed the higher plasma MDA levels compared with those with mild acne. The lowest MDA levels were observed in acne free individuals. Conclusion Serum MDA level is elevated in patients with acne than in acne free individuals. IPL can be used as a monotherapy in acne , especially in inflammatory lesions. IPL is effective in reducing oxidative stress in acne .

Most studies on the skin focus primarily on the hair follicle and interfollicular epidermis, whereas little is known regarding the homeostasis of the sebaceous gland (SG). The SG has been proposed to be replenished by different pools of hair follicle stem cells and cells that resides in the SG base, marked by Blimp1. Here, we demonstrate that single Blimp1+ cells isolated from mice have the potential to generate SG organoids in vitro. Mimicking SG homeostasis, the outer layer of these organoids is composed of proliferating cells that migrate inward, undergo terminal differentiation and generating lipid-filled sebocytes. Performing confocal microscopy and mass-spectrometry, we report that these organoids exhibit known markers and a lipidomic profile similar to SGs in vivo. Furthermore, we identify a role for c-Myc in sebocyte proliferation and differentiation, and determine that SG organoids can serve as a platform for studying initial stages of acne vulgaris, making this a useful platform to identify potential therapeutic targets., The sebaceous gland (SG) has been proposed to be replenished by pools of cells, including a population in the SG base, marked by Blimp1. Here, the authors show that Blimp1+ cells can establish an organoid model of the SG, which is regulated by c-Myc and can recapitulate the early stages of acne vulgaris.

The histogenesis of extraocular sebaceous carcinomas is - in contrast to ocular sebaceous carcinomas - unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki-67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63+ K5+ progenitors which generate the K10+ luminal cells of sebaceous ducts; and (ii) p63+ K5+ K7+ progenitors which finally generate K7+ adipophilin+ EMA+ sebocytes. Without exception, all types of sebaceous tumors contained p63+ K5+ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin+ and/or EMA+ mature sebocytes and to K10+ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63+ K5+ cells play a major role.

In this study, we determined the nutritional and functional components in blossom and bee pollen from Rosa rugosa and evaluated their effects on acne caused by excessive androgen secretion based on the golden hamster acne model. Blossom and bee pollen extract from Rosa rugosa had beneficial effects on reducing the area of the sebaceous glands, decreasing TG levels in the sebaceous glands, decreasing the release of IL-1α and TNF-α, alleviating the release of MMP-2 and MMP-9, increasing the content of caspase-3, reducing the release of testosterone T, and increasing the release of estrogen E2. Both blossom and bee pollen extract from Rosa rugosa could alleviate acne caused by excessive androgenic secretion. In addition, bee pollen extract may have better effects on alleviating the release of inflammatory cytokines and MMPs, and promoting the degree of apoptosis. However, blossom extract may have better effects on regulating the levels of sex hormone.

The epidermis consists of different compartments such as the hair follicle (HF), sebaceous gland (SG) and interfollicular epidermis (IFE), each containing distinct stem cell (SC) populations. However, with the exception of the SCs residing within the HF bulge, other epidermal SC populations remain less well understood. Here we used an epigenomic strategy that combines H3K27me3 ChIP-seq and RNA-seq profiling to identify major regulators of pilosebaceous unit (PSU) SC located outside the bulge. When applied to the bulk of PSU SC isolated from mouse skin our approach identified both previously known and potentially novel non-bulge PSU SC regulators. Among the latter, we found that PRDM16 was predominantly enriched within the Junctional Zone (JZ), which harbors SC that contribute to renewal of the upper HF and the SG. To investigate PRDM16 function in the PSU SC, we generated an epidermal-specific Prdm16 Knock-out mouse model (K14-Cre-Prdm16fl/fl). Notably, SG homeostasis was disturbed upon loss of PRDM16 resulting in enlarged SGs, and excessive sebum production, resembling some of the features associated with human acne and sebaceous hyperplasia. Importantly, PRDM16 is essential to shut down proliferation in differentiating sebocytes. Overall, our study provides a list of putative novel regulators of PSU SC outside the bulge and identifies PRDM16 as a major regulator of SG homeostasis.

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.

Delgocitinib ointment 0.5% is the world’s first topical Janus kinase inhibitor product and was approved for treatment of atopic dermatitis (AD) in Japan. Although topical corticosteroids (TCSs) have been the mainstay of pharmacotherapy in AD over the past decades, long-term use of TCSs causes skin atrophy and alteration of the epidermal tight junction (TJ) leading to epidermal barrier dysfunction. In this study, delgocitinib ointment 0.5% or representative TCSs of different potencies were applied dermally once daily to the ear pinna of normal ICR mice for 14 days, and ear pinna thickness, histopathology, and immunohistochemistry for epidermal TJ proteins claudin-1 and -4 were evaluated. All the TCSs caused decreases in ear pinna thickness with epidermal thinning, sebaceous gland atrophy, and atrophy/decreased number of the subcutaneous adipocytes and decreased immunohistochemical staining intensity for epidermal claudins. In contrast, delgocitinib ointment 0.5% did not cause any of those changes. In conclusion, once daily topical delgocitinib ointment 0.5% for 14 days did not cause skin atrophy or decreased immunohistochemical staining of epidermal claudins, which are common safety concerns associated with TCSs. These characteristics suggest that delgocitinib ointment 0.5% has an improved safety profile over currently available TCS therapies particular for the long-term AD treatment.

Glandula uropygialis (uropygial bez), kuşlarda derinin holokrin yapıda bir yağ bezidir. Bu çalışma erkek peçeli baykuşlarda (Tyto alba) uropygial bezin morfolojik ve histolojik yapısını belirlemek amacıyla yapıldı. Çalışmada erişkin yaşta 4 adet erkek peçeli baykuş materyali kullanıldı. Kuşların kuyruk bölgesinde yer alan bezler diseke edilerek vücuttan ayrıldı. Bezlerin morfometrik incelemeleri yapıldı. Bezin histolo- jik yapısını ortaya koyabilmek amacıyla doku kesitleri Hematoksilen & Eozin (H&E) ve Masson Trichrome yöntemleri ile boyandı. Boyanan kesitler ışık mikroskobu ile incelendi. Topografik incelemede, bezin synsakrumun kaudalinde, kuyruk omurlarının üzerinde yerleştiği belirlendi. Bezin ortalama ağırlığı 0.493±0.02 g, relatif indeks değeri (bez ağırlığının vücut ağırlığına oranı) ise 0.10±0.01 olarak bulundu. Histomorfolojik incelemede her bir lobun dışarıdan bağ doku ile sarıldığı görüldü. Loblar sıralı olarak dizilmiş tubulo-alveolar bezlerden oluşmaktaydı. Bezler ince bağ doku ile sınırlandırılarak birbirinden ayrılmışlardı. Bezler arasındaki bağ doku içerisinde kan damarları yer almaktaydı. Bezler kranialden kaudal uca doğru gidildikçe şekil ve hücre dizilişi bakımından farklılık gösteren 3 farklı bölgeden oluşmaktaydı. Sonuç olarak peçeli baykuş uropygial bezinin gerek morfolojik gerek histolojik yapısı bir takım yapısal farklılıklara rağmen literatürlerde bildirilen diğer birçok kanatlı hayvanlardaki ile benzerdi. The glandula uropygialis (uropygial gland) is a holocrine sebaceous gland of the skin in birds. This study was carried out to determine the morphological and histological structure of the uropygial gland in male barn owls (Tyto alba). In this study, four adult male barn owl materials were used. The glands in the tail area of the birds were dissected and separated from the body. Morphometric examinations were made of the glands. Tissue sections were stained with Hematoxylin & Eosin (H&E) and Masson Trichrome methods to reveal the histological structure of the gland. The stained sections were examined with by light microscope. In topographical examination, it was determined that the gland was located in the caudal of the synsacrum, above the tail vertebrae. The average weight of the gland was found 0.493 ± 0.02 g, and the relative index value (ratio of gland weight to body weight) was found 0.10 ± 0.01. In histomorphological examination, it was seen that each lobe was externally surrounded by connective tissue. The lobes consisted of sequentially lined tubulo-alveolar glands. The glands were separated by a thin connective tissue. There were blood vessels in the connective tissue between the glands. The glands consisted of 3 different regions that differ in shape and cell sequence to throught from the cranial to the caudal end. As a result, the morphological and histological structure of the barn owl uropygial gland was similar to many other poultry animals reported in the literature, despite some structural differences.

Acne vulgaris, commonly known as acne, is the most common skin disorder and a multifactorial disease of the sebaceous gland. Although the pathophysiology of acne is still unclear, bacterial and fungal factors are known to be involved in. This study aimed to investigate whether the microbiomes and mycobiomes of acne patients are distinct from those of healthy subjects and to identify the structural signatures of microbiomes related to acne vulgaris. A total of 33 Korean female subjects were recruited (Acne group, n = 17; Healthy group, n = 16), and microbiome samples were collected swabbing the forehead and right cheek. To characterize the fungal and bacterial communities, 16S rRNA V4-V5 and ITS1 region, respectively, were sequenced and analysed using Qiime2. There were no significant differences in alpha and beta diversities of microbiomes between the Acne and Healthy groups. In comparison with the ratio of Cutibacterium to Staphylococcus, the acne patients had higher abundance of Staphylococcus compared to Cutibacterium than the healthy individuals. In network analysis with the dominant microorganism amplicon sequence variants (ASV) (Cutibacterium, Staphylococcus, Malassezia globosa, and Malassezia restricta) Cutibacterium acnes was identified to have hostile interactions with Staphylococcus and Malassezia globosa. Accordingly, this results suggest an insight into the differences in the skin microbiome and mycobiome between acne patients and healthy controls and provide possible microorganism candidates that modulate the microbiomes associated to acne vulgaris.

The harlequin mutation arose spontaneously in the outbred CFl stock at the Instituto Carlo Erba in Italy. Two hemizygous males were examined and found to have a mixture of hair types that contained both eumelanin and phaeomelanin. The predominant lesion found in this mutation by scanning electron microscopic examination of plucked hairs is the breaking of the hair shaft near the bulb end. The break appeared to be clean and was found within the first quarter-length of the hair shaft. Follicles in anagen on the tail skin produced normal, large hair shafts. Skin biopsies from the areas of alopecia revealed deformed and broken hair shafts within the piliary canal extending from the level of the sebaceous gland to the surface. Follicles containing large amounts of distorted hair shafts exhibited hyperplasia of the outer root sheath. The harlequin mouse mutation may have value as a tool to investigate hair structure, follicular biochemistry, and treatments for defective hair.

Multidisciplinary investigations into the pathogenesis of acne have significantly progressed over the past three years. Studies of the etiology of acne from the perspectives, for example, of sebaceous gland biology, sebum, genetics, keratinization, differentiation, hair cycles, immunology, bacteriology, and wound healing have elucidated its pathogenesis. This has led to the development of new therapies and paved the way for advanced studies that will enable the further evolution of acne treatment.

Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). Although many factors, such as aging, androgen deficiency, bacterial colonization and drug toxicity have been demonstrated to be associated with MGD, its pathogenesis is not well understood and definite therapies are lacking. Meibomian gland is the largest lipid-secreting gland of human and is the counterpart of sebaceous gland in the eyelid. The lipophilic yeast Malassezia species (spp) habitats in sebaceous gland and is generally considered to play pathogenic roles in seborrheic dermatitis. Several mechanisms have been illuminated, including secretion of lipases, production of toxic metabolites and generation of reactive oxidative species. Anti-fungal therapy is beneficial for patients with seborrheic dermatitis. So far, no previous studies have investigated the link between Malassezia spp and MGD. But there are reports which demonstrate increased prevalence of both high delivery and obstructive MGD in patients with seborrheic dermatitis. Malassezia spp is also found to be associated with anterior blepharitis, the seborrheic inflammation of the other counterpart of sebaceous gland in the eyelid-the Zeis gland. Based on the pathogenic role of Malassezia spp and its highly lipophilic characteristic, we hypothesize that Malassezia spp may also habitat in meibomian gland and play potential pathogenic roles in MGD. Anti-fungal treatment with 2% ketoconazole cream may be potential therapy for patients with MGD. If the hypothesis can be confirmed on patients, it can provide a novel insight of the pathogenesis of MGD and hopefully trigger further investigation into the relationship between microbiota colonization and the function of meibomian gland.

In 2018, Schneider and Zouboulis analysed the available tools for studying sebaceous gland pathophysiology in vitro. Since then, the interest in this field remains unbroken, as demonstrated by recent reviews on sebaceous gland physiology, endocrinology and neurobiology, the role of sebaceous glands beyond acne, and several original works on different areas of sebaceous gland function, including sebaceous lipogenesis. Landmark developments in the first part of the 30-year modelling research dedicated to the sebaceous gland, which is considered by several scientists as the brain of the skin, were the short-term culture of human sebaceous glands, the culture of human sebaceous gland cells and the development of immortalized sebaceous gland cell lines exhibiting characteristics of normal sebocytes. On the other hand, current developments represent the establishment of sebaceous gland spheroids, the 3D-SeboSkin model of viable skin explants ex vivo, the combination of culture-expanded epidermal stem cells of mice and adult humans to form de novo hair follicles and sebaceous glands, when they are transplanted into excisional wounds in mice, and 3D-printed scaffolds coated with decellularized matrix of adipose-derived mesenchymal stromal cells and SZ95 sebocytes. These novel tools may become useful platforms for better understanding of cellular and molecular mechanisms governing sebocyte biology and sebaceous gland homeostasis, such as the changes in sebum synthesis and composition, the infundibular differentiation and the influence of the innate immunity and the cutaneous microbiome and for identifying potential therapeutic targets of skin diseases affecting the sebaceous glands.

Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular-junction-like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here, we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle.

The common palm civet (Paradoxurus hermaphroditus) is one of the mammalian in Indonesia which have anal gland in female and fefemale that located in the lower tail. This research was aimed to describe the morphology of anal gland of common palm civet female. One female of common palm civet was used in this research which observed macroscopic and microscopic.The result showed that common palm civet have a pair of anal gland which hasshaped like ball and located in the anal sacs wall’s in the ventrolateral of anus.Each anal gland has a ostium of anal canal dorsolaterally in the cutaneous zone of anal canal . Microscopic observation showed a well developed sebaceous gland and apocrine sweat gland in the wall of anal sac. Sebaceous and apocrine glands were excreted their product into main ductus to the anal canal.

Skin becomes the largest organ in the body and protects its own inner layer. The structure and chemical composition of the skin contribute to skin condition and affect the habitat of certain bacteria. The Sunda Porcupine is one of endemic animals of Indonesia which possesses quill as the main derivate of its skin and as a defence tool against predators. The present study used nine adults (five females and four males) of Sunda Porcupine and aimed to observe the correlation of skin structure with bacterial population at the surface level. The skin was wavy due to the protrusion of quill follicle orifices on the skin surface and formed clusters. The skin of Sunda Porcupine was also wrinkled and had a lot of flakiness. Histologically, the skin was composed of epidermis, dermis, hypodermis and subcutaneous muscle. The quill follicles and their properties were the dominant structure component of the skin. No sweat gland was observed in the skin of the Sunda Porcupine, and sebaceous gland was found only around quill and hair follicles. The bacterias identified in the skin were Staphylococcus aureus, S. epidermidis, Micrococcus sp. and Salmonella sp. When compared, the bacterial population was higher in the lumbosacral region than in the thoracodorsal region, but the difference was not significant. The density of quill clusters was negatively correlated to the bacterial population. It was suggested the structure of the skin has contribution to bacterial population in dorsal trunk of the Sunda Porcupine.

Management of dairy cow productivity requires monitoring of their nutritional status by visual observation. It has been suggested that changes in hair coat appearance are among the indicators of nutritional state in dairy cows. Temporal changes in the skin morphology in cows, however, have not been reported. In this study, we examined the changes in the skin of dairy cows that occur during the peripartum period. Seven pluriparous cows were used. Skin samples were collected at 28 d before the due date and 28 d and 56 d after calving for morphological examination. Hair follicle width was 108.8 ± 5.9 µm (±SD) in the dry period, 95.5 ± 5.5 µm at 28 d after calving, and 104.2 ± 5.3 µm at 56 d postpartum. The percentages of anagen hair follicles during these 3 periods were 41.4 ± 3.4, 18.5 ± 3.4, and 32.3 ± 3.3%, respectively. The corresponding sebaceous gland sizes were 8,362.0 ± 707.6, 7,800.0 ± 831.4, and 9,186.8 ± 962.6 µm2, respectively. Hair follicle width was positively correlated with percentage of anagen hair follicles. The thickness of epidermal and proliferation rate of epidermal cell were also correlated. However, the hair follicle width, sebaceous gland size and cell proliferation rate, and thickness and proliferation rate of epidermal cells did not show any marked changes.

Recognised for its key role in lactation, it is less well appreciated that the neurohormone prolactin (PRL) is actually one of the most pleiotropic hormones known. Not only does PRL exert both tropic and trophic effects in a wide range of tissues, but it is also expressed in human skin and hair follicles and regulates multiple complex cutaneous functions, including keratin expression and hair growth. Despite several clinical indications that PRL may also play a role in sebaceous gland (SG) biology, the effects of PRL on SG function have received little attention. In this Viewpoint essay, we argue that PRL may be a sebotrop(h)ic hormone and could represent a novel therapeutic target in human dermatoses affecting the SG. We provide preliminary evidence in support of this hypothesis (based on findings in human skin organ culture) and chart the major open questions in SG biology and pathology from a PRL research perspective. We close by delineating how these questions can be experimentally addressed so as to identify new therapeutic strategies that are either sebogenic or sebostatic, for example in the management of acne and cutaneous ageing.

The study was carried out on a total of 250 Gir cattle, which covered those presented to the Veterinary Clinical Complex of the College in Junagadh (Gujarat) for therapeutic measures and some from Gaushala near to Junagadh region. The animals were screened for common hemoprotozoan infection based on blood smear examination to record the prevalence rate of infection. The overall prevalence of hemoprotozoan infections recorded on the basis of microscopic examination of blood smears was 35.20 %. Out of these, 64 (25.60%) were positive for Theileria spp., 20 (8%) for Babesia spp., and 4 (1.6%) for Anaplasma spp. a highest prevalence was recorded in April (64.70%), followed by March (57.14%) and February (42.85%). The lowest prevalence was recorded in the month of December (5.88%). The highest prevalence was recorded in the summer season (40.71%), followed by rainy (34.37%) and winter season (19.56%). The highest prevalence of hemoprotozoan infection (41.86%) was recorded in Gir cattle of 3 to 8 years age group followed by 32.35% in 6 months to 3 years age group, and the lowest prevalence was recorded (24.32%) in older animals 8 years and above age group.

Breed predispositions to canine digital neoplasms are well known. However, there is currently no statistical analysis identifying the least affected breeds. To this end, 2912 canine amputated digits submitted from 2014–2019 to the Laboklin GmbH &amp, Co. KG for routine diagnostics were statistically analyzed. The study population consisted of 155 different breeds (most common: 634 Mongrels, 411 Schnauzers, 197 Labrador Retrievers, 93 Golden Retrievers). Non-neoplastic processes were present in 1246 (43%), tumor-like lesions in 138 (5%), and neoplasms in 1528 cases (52%). Benign tumors (n = 335) were characterized by 217 subungual keratoacanthomas, 36 histiocytomas, 35 plasmacytomas, 16 papillomas, 12 melanocytomas, 9 sebaceous gland tumors, 6 lipomas, and 4 bone tumors. Malignant neoplasms (n = 1193) included 758 squamous cell carcinomas (SCC), 196 malignant melanomas (MM), 76 soft tissue sarcomas, 52 mast cell tumors, 37 non-specified sarcomas, 29 anaplastic neoplasms, 24 carcinomas, 20 bone tumors, and 1 histiocytic sarcoma. Predisposed breeds for SCC included the Schnauzer (log OR = 2.61), Briard (log OR = 1.78), Rottweiler (log OR = 1.54), Poodle (log OR = 1.40), and Dachshund (log OR = 1.30). Jack Russell Terriers (log OR = −2.95) were significantly less affected by SCC than Mongrels. Acral MM were significantly more frequent in Rottweilers (log OR = 1.88) and Labrador Retrievers (log OR = 1.09). In contrast, Dachshunds (log OR = −2.17), Jack Russell Terriers (log OR = −1.88), and Rhodesian Ridgebacks (log OR = −1.88) were rarely affected. This contrasted with the well-known predisposition of Dachshunds and Rhodesian Ridgebacks to oral and cutaneous melanocytic neoplasms. Further studies are needed to explain the underlying reasons for breed predisposition or “resistance” to the development of specific acral tumors and/or other sites.

Acne is a chronic inflammatory disease of the pilosebaceous unit. Its pathophysiology includes hyperseborrhoea, abnormal follicular keratinization and Propionibacterium acnes proliferation in the pilosebaceous unit. Recent research has shed some new light on the involvement of the sebaceous gland, as well as on the pro-inflammatory activity of the cutaneous microbiome. During puberty, alteration of the sebaceous lipid profile, called dysseborrhoea, stress, irritation, cosmetics and potential dietary factors lead to inflammation and formation of different types of acne lesions. Dysbiosis, the process leading to a disturbed skin barrier and disequilibrium of the cutaneous microbiome, resulting in the proliferation of P. acnes strains, is another important process that triggers acne. P. acnes activates the innate immunity via the expression of protease activated receptors (PARs), tumour necrosis factor (TNF) α and toll-like receptors (TLRs), and the production of interferon (INF) γ, interleukins (IL-8, IL12, IL-1), TNF, and matrix metalloproteinases (MMPs) by keratinocytes, resulting in the hyperkeratinization of the pilosebaceous unit. Rebalancing the natural microbiome of the skin by restoring the natural skin barrier, limiting the proliferation of P. acnes on the skin by using topical antibacterials which do not cause resistance and regulating quantity and quality of sebum will be the main acne treatment challenges in the future. The aim of this article to provide an update on the involvement of the sebaceous gland, the innate immunity and the cutaneous microbiome, how all of these factors promote acne and to illustrate their links with current and future treatments.

The skin is an endocrine organ with the expression of metabolizing enzymes and hormone receptors for diverse hormones. The sebaceous gland is the main site of hormone biosynthesis, especially for androgens, and acne is the classical androgen-mediated dermatosis. In sebocytes, conversion of 17-hydroxyprogesterone directly to dihydrotestosterone bypassing testosterone has been demonstrated, while type II 17β-hydroxysteroid dehydrogenase can inactivate the action of testosterone and dihydrotestosterone. The androgen receptor-dependent genomic effect of dihydrotestosterone on sebocytes is confirmed. Further evidence supports the PI3 K/Akt/FoxO1/mTOR signaling in the involvement of the interplay between androgens, insulin, insulin-like growth factor, and hyperglycemic diet in acne. Androgens not only regulate embryology and lipogenesis/sebum synthesis in sebocytes but also influence inflammation in acne. Genetic studies indicate that regulation of the androgen receptor is an important factor in severe acne. Further studies are required to understand the effect of estrogen and progesterone on sebaceous gland and comedogenesis, considering the change of acne in pregnancy and postmenopausal acne. Special attention should be paid to nonobese patients with polycystic ovarian syndrome and hyperandrogenism-insulin resistance-acanthosis nigricans syndrome. In spite of extensive gynecologic experience in the use of combined oral contraceptives for acne, evidence based on dermatologic observation should be intensified.

The Wilms’ tumour gene (WT1) has previously been described as an oncogene in several neoplasms of humans, including melanoma, and its expression increases cancer cell proliferation. Recent reports associate the expression of the PPARβ/δ gene (peroxisome proliferator-activated receptor beta/delta) with the downregulation of WT1 in human melanoma and murine melanoma cell lines. The aim of this work was to analyse the expression of WT1 and its association with PPARβ/δ in samples of healthy and melanoma-affected skin of horses by immunohistochemistry. WT1 protein expression was detected in healthy skin, mainly in the epidermis, hair follicle, sebaceous gland and sweat gland, while no expression was observed in equine melanoma tissues. Moreover, it was observed that PPARβ/δ has a basal expression in healthy skin and that it is overexpressed in melanoma. These results were confirmed by a densitometric analysis, where a significant increase of the WT1-positive area was observed in healthy skin (128.66 ± 19.84 pixels 106) compared with that observed in melanoma (1.94 ± 0.04 pixels 106). On the other hand, a positive area with an expression of PPARβ/δ in healthy skin (214.94 ± 11.85 pixels 106) was significantly decreased compared to melanoma (624.86 ± 181.93 pixels 106). These data suggest that there could be a regulation between WT1 and PPARβ/δ in this disease in horses.

Objective To identify the time window during which the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a key role in telogen-to-anagen transition of hair follicles, and to explore whether the pathway specifically promotes the proliferation of hair follicle stem cells (HFSCs) . Methods Totally, 36 newborn ICR mice were randomly and equally divided into 3 groups: RAPA-P19 group intraperitoneally injected with 5 mg·kg-1·d-1 sirolimus on days 19-24 after birth, RAPA-P21 group intraperitoneally injected with 5 mg·kg-1·d-1 sirolimus on days 21-24 after birth, and control group intraperitoneally injected with the same volume of solvent on days 19-24 after birth. Four mice were sacrificed in each group on days 22, 23 and 24 separately. Skin tissues were resected from the back, and hematoxylin-eosin staining of the skin tissues were performed followed by observation of hair follicle morphology to evaluate whether murine hair follicles progressed into the anagen phase on day 24. Immunofluorescence costaining was conducted to determine the expression and localization of mTORC1 downstream molecular marker pS6 and cell proliferation marker Ki67 on days 22 and 23. Results On day 24, hematoxylin-eosin staining showed anagen hair follicles in the control group and RAPA-P21 group, but telogen hair follicles in the RAPA-P19 group. On days 22 and 23, immunofluorescence costaining revealed positive staining for both pS6 and Ki67 in HFSCs in the control group, negative staining for both pS6 and Ki67 in the RAPA-P19 group, negative staining for pS6 and positive staining for Ki67 in the RAPA-P21 group. On day 23, epidermal cells and sebaceous gland cells in the upper hair follicle bulge were stained positively for Ki67 in all the 3 groups. Conclusion mTORC1 signaling specifically promotes the proliferation of HFSCs during telogen-to-anagen transition, but not affects proliferation of other cells in hair follicles. Key words: Hair follicle; Stem cells; Cell proliferation; Sirolimus; Hair cycle; Time window; mTORC1