Endocrinology and immunology of acne: Two sides of the same coin.

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.

Why do humans get acne? A hypothesis.

Acne is a disease unique to humans and is associated with sebaceous glands that are found at high density on the scalp, forehead and face. Despite being a near universal problem in adolescence, the reason why such troublesome sebaceous glands exist at all is not well understood. Some interesting theories have been postulated including roles for skin maintenance, immunological function and perhaps even pheromones, but pre-pubertal skin which has sebaceous glands that are largely inactive, is healthy. Dystocia, obstructed labour, is unique to humans and no other animal has as much trouble giving birth. This is thought to reflect the relatively large human foetal head and proportionally small maternal pelvis. Noting the high density of sebaceous glands on the face, chest and back; these are exactly the same structures that pose the greatest obstruction during childbirth. Sebaceous glands develop after the fourth month of gestation and are large and well-developed at birth. Sebum production is also relatively high at birth. Having extra lubrication at these sites would help make the baby more slippery for birth conferring a selective advantage to successful delivery, as does the presence of the vernix caseosa, a white creamy substance, unique to humans that coats new-born infants. It is proposed that the sebaceous glands that cause acne are present on the face and forehead as they confer a selective advantage by 'lubricating' the widest parts of the new born baby to ease the passage of childbirth. Later in life, sebaceous glands may be inappropriately and pathologically primed, driven by a combination of hormones, diet and lifestyle to create acne.

Relationship of transcutaneous oxygen tension with age and skin elasticity in Korean women.

BACKGROUND: Oxygen has several positive effects on the skin, including improving collagen synthesis and accelerating wound healing. However, only a few studies have investigated the relationship between skin oxygenation and skin aging parameters. Therefore, this study aimed to assess the correlation between skin oxygenation and skin aging parameters-elasticity, hydration, sebum, color (lightness, redness), and blood perfusion-in Korean women. MATERIALS AND METHODS: We evaluated the transcutaneous partial pressure of oxygen, also known as transcutaneous oxygen tension (TcPO2 ), and skin aging parameters, including elasticity, hydration, sebum, color (lightness or redness), and blood perfusion, in the cheek of 34 healthy women (aged 20-69 years) and assessed the correlation between TcPO2 and other skin aging parameters using IBM SPSS Statistics 25 software (SPSS Inc). RESULTS: Facial TcPO2 was negatively correlated with age (P < .05). There were positive correlations between facial TcPO2 and elasticity parameters (P < .01). We noted no correlation between facial TcPO2 and skin lightness; however, skin lightness tended to slightly improve with increasing TcPO2 . Skin aging parameters, including hydration, sebum, skin redness, and blood perfusion, showed no correlations with TcPO2 . CONCLUSION: In Korean women, facial TcPO2 tends to decrease with increasing age and is positively correlated with gross, net, and biological skin elasticity. Therefore, this study demonstrated that oxygen tension of facial skin can be a major causative factor of skin aging.

Repeated measurements of facial skin characteristics using the Janus-â ¢ measurement system.

BACKGROUND: For personalized skin care, noninvasive quantitative methods to evaluate facial skin characteristics are important. Janus-III is one of the most widely used imaging analysis devices in the skin care industry in Korea. Janus-III generates values for a range of skin characteristics. Due to the convenience of obtaining results for a variety of skin characteristics in a single measurement, the use of Janus-III in cosmetic stores and research institutes has been recently increasing. However, the consistency of skin measurements of Janus-III has not been elucidated yet. MATERIALS AND METHODS: In this study, we repeated skin measurements three times for 70 different subjects and compared each numerical value in order to assess the consistency of the Janus-III. For this purpose, we compared between-sample distances and within-sample distances. RESULTS: We found important patterns for future analyses in terms of consistency. First, the average values of skin measurement categories were more reliable than individual part values of facial segments. Second, center part values such as forehead and nose were more reliable than side part values such as left and right part segments. CONCLUSION: If researchers who use Janus-III for studies of facial characteristics analyze average and center part values first, they can obtain relatively reliable patterns of facial skin characteristics.

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin.

BACKGROUND: Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT. OBJECTIVES: To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[14C]PT was investigated. METHOD: In vitro penetration of [14C]PT into and through excised human skin was measured following application of Zn[14C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum. RESULTS: The steady-state flux and cumulative absorption of Zn[14C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[14C]PT and 3H2O absorption when dosed from both aqueous formulations, but not from castor oil. CONCLUSION: These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [14C]PT kinetics, is controlled by particle dissolution and molecular speciation.

Changes in Fingerprints Depending on Physiological Factors.

The aim of the study was to determine the effect of gender, body mass index, and time on the width of friction ridge impressions in fingerprints and the content of sweat and sebum forming the print. The research showed that the friction ridge impressions of women are significantly wider than those of men, and this tendency persists throughout the existence of the print. The differences may result from the anatomical structure of the skin, as well as from the use of protective products such as creams, which are used more often by women. The width of friction ridge impression is similar in underweight and overweight people, but greater than in those with normal body weight, and the amount of sweat and sebum increases with body weight. The passage of time significantly reduces both the width of the friction ridge impression and the content of sweat and sebum secretions in the print.

Influence of the sebaceous gland density on the stratum corneum lipidome.

The skin surface lipids (SSL) result from the blending of sebaceous and epidermal lipids, which derive from the sebaceous gland (SG) secretion and the permeability barrier of the stratum corneum (SC), respectively. In humans, the composition of the SSL is distinctive of the anatomical distribution of the SG. Thus, the abundance of sebum biomarkers is consistent with the density of the SG. Limited evidence on the influence that the SG exerts on the SC lipidome is available. We explored the differential amounts of sebaceous and epidermal lipids in areas at different SG density with lipidomics approaches. SC was sampled with adhesive patches from forearm, chest, and forehead of 10 healthy adults (8F, 2M) after mechanical removal of sebum with absorbing paper. Lipid extracts of SC were analysed by HPLC/(-)ESI-TOF-MS. In the untargeted approach, the naïve molecular features extraction algorithm was used to extract meaningful entities. Aligned and normalized data were evaluated by univariate and multivariate statistics. Quantitative analysis of free fatty acids (FFA) and cholesterol sulfate (CHS) was performed by targeted HPLC/(-)ESI-TOF-MS, whereas cholesterol and squalene were quantified by GC-MS. Untargeted approaches demonstrated that the relative abundance of numerous lipid species was distinctive of SC depending upon the different SG density. The discriminating species included FFA, CHS, and ceramides. Targeted analyses confirmed that sebaceous FFA and epidermal FFA were increased and decreased, respectively, in areas at high SG density. CHS and squalene, which are biomarkers of epidermal and sebaceous lipid matrices, respectively, were both significantly higher in areas at elevated SG density. Overall, results indicated that the SG secretion intervenes in shaping the lipid composition of the epidermal permeability barrier.

Skin care and rejuvenation by cosmeceutical facial mask.

Skin health is an important aspect of aesthetics. Dermatologists and scientists try to develop novel methods and materials to fulfill this aim. Facial cosmetics keep skin moist and remove sebum from the skin to maintain proper skin health. The use of suitable cosmetics according to the facial skin type results in healthy skin. Facial masks are the most prevalent cosmetic products utilized for skin rejuvenation. Facial masks are divided into four groups: (a) sheet masks; (b) peel-off masks; (c) rinse-off masks; and (d) hydrogels. Each of these has some advantages for specific skin types based on the ingredients used. The following article presents the available information about the facial mask. Also, we have focused on the facial masks available in the market. Despite several developments in this field, extensive research is required for performing successful and precise clinical trials in the future. Further improvements would enable the researchers to develop new products in this field. In this review, we present the most recent breakthroughs in the field of skin care and rejuvenation by cosmeceutical facial mask. This information is valuable to get the picture of the latest trends and also helpful for clinicians and related manufacturing companies.

Determining the Effect of pH on the Partitioning of Neutral, Cationic and Anionic Chemicals to Artificial Sebum: New Physicochemical Insight and QSPR Model.

PURPOSE: Sebum is an important shunt pathway for transdermal permeation and targeted delivery, but there have been limited studies on its permeation properties. Here we report a measurement and modelling study of solute partition to artificial sebum. METHODS: Equilibrium experiments were carried out for the sebum-water partition coefficients of 23 neutral, cationic and anionic compounds at different pH. RESULTS: Sebum-water partition coefficients not only depend on the hydrophobicity of the chemical but also on pH. As pH increases from 4.2 to 7.4, the partition of cationic chemicals to sebum increased rapidly. This appears to be due to increased electrostatic attraction between the cationic chemical and the fatty acids in sebum. Whereas for anionic chemicals, their sebum partition coefficients are negligibly small, which might result from their electrostatic repulsion to fatty acids. Increase in pH also resulted in a slight decrease of sebum partition of neutral chemicals. CONCLUSIONS: Based on the observed pH impact on the sebum-water partition of neutral, cationic and anionic compounds, a new quantitative structure-property relationship (QSPR) model has been proposed. This mathematical model considers the hydrophobic interaction and electrostatic interaction as the main mechanisms for the partition of neutral, cationic and anionic chemicals to sebum.

A review of the role of sebum in the mechanism of acne pathogenesis.

Acne is one of the most common skin disorders, and its occurrence is closely related to many factors, including sebum secretion, hormone levels, bacterial infection, and inflammatory reactions. Among these, changes in sebum secretion are believed to be one important factor of acne. Increased sebum secretion can induce acne occurrence, and increasing evidence indicates sebum component changes are also strongly related to acne occurrence. Recently, developments in lipidomics have provided effective lipid analysis methods. These can help elucidate the effects of different types of sebum on acne occurrence and provide a theoretical basis for research on the mechanisms of acne pathogenesis and treatment.

Topical Treatment With an Agent Disruptive to P. acnes Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial.

The traditional disease model of acne has been one of follicular plugging due to 'sticky epithelial cells' associated with increased sebum production with deep follicular anaerobic conditions favoring P. acnes- generated inflammation. P. acnes biofilms have been found more frequently in patients with acne than controls. Biofilms are genetically coded to create adhesion to the pilosebaceous unit followed by production of a mucopolysaccharide coating capable of binding to lipid surfaces. Traditional therapies for acne have involved mixtures of oral and topical antibiotics admixed with topical keratolytics and retinoids, which are aimed at traditional bacterial reduction as well as downregulating the inflammatory cascade. These approaches are limited by side effect and compliance/tolerability issues. As the P. acnes biofilm may, in fact, be the instigator of this process, we studied the use of a topical agent designed to reduce the P. acnes biofilm to see if reducing the biofilm would be therapeutically efficacious. We present data of a proprietary topical non-prescription agent with a novel pharmaco mechanism designed to attack the biofilm produced by P. acnes. Our data shows a decrease of inflammatory lesions by 44% and non-inflammatory lesions by 32% after 12 weeks and also provided for a meaningful improvement in the quality of life of the patients in the study. These improvements were achieved with a product that was not associated with burning, chafing, irritation, or erythema, which can be seen with topical treatments. It is apparent from this study that by addressing the biofilm which protects the P. acnes bacteria through the use of the Acne Gel, the incidence of acne symptoms can be greatly reduced, while having no negative impacts on the patients' skin (ClinicalTrials.gov registry number NCT02404285).

J Drugs Dermatol. 2016;15(6):677-683.

Skin barrier in rosacea.

Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea.

Skin barrier in rosacea

Abstract Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea.

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.

The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.

The investigation of the skin characteristics of males focusing on gender differences, skin perception, and skin care habits.

BACKGROUND/PURPOSE: Various studies have examined the properties of male skin. However, because these studies mostly involved simple measurement with non-invasive devices, a lack of understanding of the properties of male skin remains. METHODS: In this study, we focused and investigated not only on simple instrumental measurements but also on gender differences and men's subjective perceptions of skin and daily skin care habits. RESULTS: Barrier function depends on corneocyte maturation level as well as sebum amount. Irrespective of the skin type, a high percentage of male subjects perceived a 'tacky feeling'. However, the percentage of men perceiving a 'shiny feeling' differed by skin type. Furthermore, there was a relationship between skin care habits and skin function. Men who did not perform a daily skincare regimen demonstrated a significantly higher sebum amount and transepidermal water loss value than those who did perform a daily skincare regimen. CONCLUSION: The results of this study indicate that male skin has two specific characteristics: impaired barrier function because of the excess amount of sebum and a lack of an appropriate skin care regimen because of the 'tacky feeling' caused by excess sebum.

Effect of preen oil on plumage bacteria: an experimental test with the mallard.

Feathers are essential for avian thermoregulation, communication or flight and a reduction of plumage condition may alter these functions and reduce individual fitness. Recently, descriptive studies provided evidence that birds carry feather-degrading bacteria on their plumage that have the ability to degrade feathers rapidly under laboratory conditions. If such bacteria reduce avian fitness, natural selection should favour the evolution of anti-bacterial defences to limit the effects of these detrimental microorganisms. Preening behaviour and associated preen gland secretions have been proposed as the main factor used by birds to limit feather-degrading bacterial growth and some recent in vitro studies provided evidence that uropygial oil inhibited the growth of some keratinolytic strains in passerines. However, preen oil antimicrobial properties remained to be experimentally tested in vivo. We conducted an experiment with mallards (Anas platyrhynchos) onto which we fixed a removable mechanism that blocked access to the uropygial gland in a first group of mallards, whilst birds in a second group had the same removable mechanism but access to their gland and a third group of birds had normal access to their gland. We found no significant effect of our treatment on total and feather-degrading bacterial loads. Three hypotheses may explain the discrepancy between our results and previous in vitro studies. First, in vitro studies may have over-estimated the bactericidal properties of the preen oil. Second, preen gland deprivation may have affected only a small portion of the feather-degrading bacterial community. Third, ducks and passerine oils might have different bactericidal properties.

Human hair follicle: reservoir function and selective targeting.

Penetration of topically applied compounds may occur via the stratum corneum, skin appendages and hair follicles. The follicular infundibulum increases the surface area, disrupts the epidermal barrier towards the lower parts of the follicle, and serves as a reservoir. Topical delivery of active compounds to specific targets within the skin, especially to distinct hair follicle compartments or cell populations, may help to treat local inflammatory reactions selectively, with reduced systemic side-effects. Various in vitro and in vivo methods exist for studying the hair follicle structure and follicular penetration pathways. These include cyanoacrylate skin surface stripping, confocal microscopy and cyanoacrylate scalp follicle biopsy. The complex anatomical structure as well as the cyclical activity of the hair follicle must be taken into consideration when designing delivery systems. In addition, delivery into and retention inside the infundibular reservoir are controlled by, for example, molecule or particle size, their polarity and the type of preparation. Preferred penetration depth and storage time must also be considered. Particles with release mechanisms should be preferred; however, the release of drugs from nanoparticles still requires further investigations.

Behavioural responses of desert gerbil, Meriones hurrianae after removal of scent marking gland.

The desert gerbil, M. hurrianae scent marks the general substratum in its territory with the sebum exudation of mid abdominal gland and urine. Having assessed number of functions, which scent marking plays in the social life of these rodents, the scent marking behaviour was studied in animals, in which the gland was surgically removed and was compared with that of intact rodents. After recovery from the operation, the scent marking frequency of both male and female M. hurrianae declined significantly and was maintained at a low level. Surprisingly, scent marking with urine also declined considerable with time. After 5 months of the operation, desert gerbils were given a choice to respond to male and female sebum odours. The frequency of their scent marking with either sebum or urine did not show any significant enhancement as compared to their initial marking rate. However, the duration of their stay and scent marking frequency near the source of the sebum odour was more that in the clean side of the cage. The role of such altering behaviors of M. hurrianae and their impact on social organization are discussed.

"Sebocytes' makeup": novel mechanisms and concepts in the physiology of the human sebaceous glands.

The pilosebaceous unit of the human skin consists of the hair follicle and the sebaceous gland. Within this "mini-organ", the sebaceous gland has been neglected by the researchers of the field for several decades. Actually, it was labeled as a reminiscence of human development ("a living fossil with a past but no future"), and was thought to solely act as a producer of sebum, a lipid-enriched oily substance which protects our skin (and hence the body) against various insults. However, due to emerging research activities of the past two decades, it has now become evident that the sebaceous gland is not only a "passive" cutaneous "relic" to establish the physico-chemical barrier function of the skin against constant environmental challenges, but it rather functions as an "active" neuro-immuno-endocrine cutaneous organ. This review summarizes recent findings of sebaceous gland research by mainly focusing on newly discovered physiological functions, novel regulatory mechanisms, key events in the pathology of the gland, and future directions in both experimental and clinical dermatology.

The effects of pajama fabrics' water absorption properties on the stratum corneum under mildly cold conditions.

BACKGROUND: The interaction of textiles with the skin is a fertile area for research. OBJECTIVE: The aim of this study was to investigate the effects of clothing fabric on the stratum corneum (SC) under mildly cold conditions. METHODS: A longitudinal controlled parallel study was designed to investigate the effects of the liquid/moisture absorption properties of pajama fabrics on the SC water content, transepidermal water loss, skin surface acidity (pH), and sebum. RESULTS: The hygroscopicity of pajama fabrics had significant associations with the SC water content and transepidermal water loss on the skin of the volunteers' backs. Sebum in the hydrophilic cotton group was slightly lower than in the polyester groups and hydrophobic cotton groups. Subjects felt warmer in the hydrophobic groups than in the hydrophilic groups. The hydrophilicity of the fabric also showed an association with overnight urinary free catecholamines. LIMITATIONS: In this study, detailed components of sebum were not analyzed. CONCLUSIONS: The hygroscopicity of the fabric may be a key factor influencing SC hydration during daily wear under mildly cold conditions.