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International Journal of Molecular... May 2016Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet... (Review)
Review
Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet environmental challenges associated with the solar day. This multi-oscillatory network is entrained by the master pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which directs an organism's rhythmic expression of physiological functions and behavior via a hierarchical system. This system has been highly conserved throughout evolution and uses transcriptional-translational autoregulatory loops. This master clock, following environmental cues, regulates an organism's sleep pattern, body temperature, cardiac activity and blood pressure, hormone secretion, oxygen consumption and metabolic rate. Mammalian peripheral clocks and clock gene expression have recently been discovered and are present in all nucleated cells in our body. Like other essential organ of the body, the skin also has cycles that are informed by this master regulator. In addition, skin cells have peripheral clocks that can function autonomously. First described in 2000 for skin, this review summarizes some important aspects of a rapidly growing body of research in circadian and ultradian (an oscillation that repeats multiple times during a 24 h period) cutaneous rhythms, including clock mechanisms, functional manifestations, and stimuli that entrain or disrupt normal cycling. Some specific relationships between disrupted clock signaling and consequences to skin health are discussed in more depth in the other invited articles in this IJMS issue on Sleep, Circadian Rhythm and Skin.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Gene Expression; Gene Expression Regulation; Humans; Skin Physiological Phenomena; Suprachiasmatic Nucleus
PubMed: 27231897
DOI: 10.3390/ijms17060801 -
Experimental Eye Research Oct 2017Meibum is a lipid-rich secretion that is produced by fully differentiated meibocytes in the holocrine Meibomian glands (MG) of humans and most mammals. The secretion is... (Review)
Review
Meibum is a lipid-rich secretion that is produced by fully differentiated meibocytes in the holocrine Meibomian glands (MG) of humans and most mammals. The secretion is a part of a defense mechanism that protects the ocular surface from hazardous environmental factors, and from desiccation. Meibomian lipids that have been identified in meibum are very diverse and unique in nature. The lipid composition of meibum is different from virtually any other lipid pool found in the human body. In fact, meibum is quite different from sebum, which is the closest secretion that is produced by anatomically, physiologically, and biochemically related sebaceous glands. However, meibum of mice have been shown to closely resemble that of humans, implying similar biosynthetic mechanisms in MG of both species. By analyzing available genomic, immunohistochemical, and lipidomic data, we have envisioned a unifying network of enzymatic reactions that are responsible for biosynthesis of meibum, which we call meibogenesis. Our current theory is based on an assumption that most of the biosynthetic reactions of meibogenesis are catalyzed by known enzymes. However, the main features that make meibum unique - the ratio of identified classes of lipids, the extreme length of its components, extensive ω-hydroxylation of fatty acids and alcohols, iso- and anteiso-branching of meibomian lipids (e.g. waxes), and the presence of rather unique complex lipids with several ester bonds - make it possible that either the activity of known enzymes is altered in MG, or some unknown enzymes contribute to the processes of meibogenesis, or both. Studies are in progress to elucidate meibogenesis on molecular level.
Topics: Bodily Secretions; Humans; Lipid Metabolism; Lipids; Meibomian Glands; Tears
PubMed: 28669846
DOI: 10.1016/j.exer.2017.06.020 -
Nutrients Jul 2022Background: Retinoids, which include isotretinoin, reduce sebum levels, the degree of epidermal wetness (CORN) and cause an increase in transepidermal water loss (TEWL).... (Randomized Controlled Trial)
Randomized Controlled Trial
Background: Retinoids, which include isotretinoin, reduce sebum levels, the degree of epidermal wetness (CORN) and cause an increase in transepidermal water loss (TEWL). Weight gain has also been observed in isotretinoin-treated patients. An agent that can reduce the severity of isotretinoin side effects is evening primrose oil (Oenothera paradoxa). The purpose of this study was to evaluate the effect of evening primrose oil supplementation in patients with acne vulgaris treated with isotretinoin on skin hydration status (CORN), transepidermal water loss (TEWL), skin oiliness (sebum) and changes in body weight and BMI. Methods: Patients diagnosed with acne were assigned to the isotretinoin-treated group (n = 25) or the isotretinoin and evening primrose oil-treated group (n = 25). The intervention lasted 9 months. CORN (with a corneometer), TEWL (with a tewameter) and sebum (with a sebumeter) were assessed twice, as well as body weight and BMI (Tanita MC-780). Results: The isotretinoin-treated group showed statistically significant reductions in CORN (p = 0.015), TEWL (p = 0.004) and sebum (p < 0.001) after the intervention. In the group treated with isotretinoin and evening primrose oil, TEWL and sebum levels also decreased significantly (p < 0.05), while CORN levels increased from 42.0 ± 9.70 to 50.9 ± 10.4 (p = 0.017). A significant decrease in body weight (p < 0.001) and BMI (p < 0.001) was observed in both groups after 9 months of intervention. Conclusions: During isotretinoin treatment, supplementation with evening primrose oil increased skin hydration. However, there were no differences between groups in transepidermal water loss, skin oiliness, weight loss and BMI.
Topics: Acne Vulgaris; Body Weight; Dietary Supplements; Humans; Isotretinoin; Linoleic Acids; Oenothera biennis; Plant Oils; Skin; Water; gamma-Linolenic Acid
PubMed: 35889936
DOI: 10.3390/nu14142980 -
Microorganisms Oct 2021The skin microbiome and sebum may be associated with inflammation-related diseases of the scalp. To assess the pathogenesis and progression of androgenetic alopecia...
The skin microbiome and sebum may be associated with inflammation-related diseases of the scalp. To assess the pathogenesis and progression of androgenetic alopecia (AGA), we analyzed the composition of sebum and the bacterial and fungal microbiomes of the scalps of 118 Japanese male individuals with and without AGA, then discussed their roles in the pathogenesis of AGA. Sebum triglyceride and palmitic acid contents were higher in the AGA group than in the non-AGA group. , a lipophilic fungus that consumes palmitic acid, was abundant on the scalps of patients with AGA. , , and were the most common genera in both groups, and patients with AGA exhibited scalp dysbiosis (increased abundance of and decreased abundance of ). Our findings suggest that both sebum and the bacterial and fungal microbiomes of the scalp may be involved in the development of AGA.
PubMed: 34683453
DOI: 10.3390/microorganisms9102132 -
Journal of Lipids 2018The primary purpose of the epidermis of terrestrial vertebrates is to produce the stratum corneum, which serves as the interface between the organism and the... (Review)
Review
The primary purpose of the epidermis of terrestrial vertebrates is to produce the stratum corneum, which serves as the interface between the organism and the environment. As such, the stratum corneum provides a permeability barrier which both limits water loss through the skin and provides a relatively tough permeability barrier. This provides for a degree of resistance to mechanical trauma and prevents or limits penetration of potentially harmful substances from the environment. The stratum corneum consists of an array of keratinized cells embedded in a lipid matrix. It is this intercellular lipid that determines the permeability of the stratum corneum. The main lipids here are ceramides, cholesterol, and fatty acids. In addition, the skin surface of mammals, including humans, is coated by a lipid film produced by sebaceous glands in the dermis and secreted through the follicles. Human sebum consists mainly of squalene, wax monoesters, and triglycerides with small proportions of cholesterol and cholesterol esters. As sebum passes through the follicles, some of the triglycerides are hydrolyzed by bacteria to liberate free fatty acids. Likewise, near the skin surface, where water becomes available, some of the ceramides are acted upon by an epithelial ceramidase to liberate sphingosine, dihydrosphingosine, and 6-hydroxysphingosine. Some of the free fatty acids, specifically lauric acid and sapienic acid, have been shown to have antibacterial, antifungal, and antiviral activity. Also, the long-chain bases have broad spectrum antibacterial activity.
PubMed: 30245886
DOI: 10.1155/2018/5954034 -
Environmental Science & Technology Jun 2022This critical review describes the squalene-ozone (SqOz) reaction, or squalene ozonolysis. Ambient ozone penetrates indoors and drives indoor air chemistry. Squalene, a... (Review)
Review
This critical review describes the squalene-ozone (SqOz) reaction, or squalene ozonolysis. Ambient ozone penetrates indoors and drives indoor air chemistry. Squalene, a component of human skin oil, contains six carbon-carbon double bonds and is very reactive with ozone. Bioeffluents from people contribute to indoor air chemistry and affect the indoor air quality, resulting in exposures because people spend the majority of their time indoors. The SqOz reaction proceeds through various formation pathways and produces compounds that include aldehydes, ketones, carboxylic acids, and dicarbonyl species, which have a range of volatilities. In this critical review of SqOz chemistry, information on the mechanism of reaction, reaction probability, rate constants, and reaction kinetics are compiled. Characterizations of SqOz reaction products have been done in laboratory experiments and real-world settings. The effect of multiple environmental parameters (ozone concentration, air exchange rate (AER), temperature, and relative humidity (RH)) in indoor settings are summarized. This critical review concludes by identifying the paucity of available exposure, health, and toxicological data for known reaction products. Key knowledge gaps about SqOz reactions leading to indoor exposures and adverse health outcomes are provided as well as an outlook on where the field is headed.
Topics: Air Pollutants; Air Pollution, Indoor; Carbon; Humans; Kinetics; Ozone; Squalene
PubMed: 35648815
DOI: 10.1021/acs.est.1c07611 -
Microbiology Spectrum Feb 2023The microorganisms inhabiting human skin must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient...
The microorganisms inhabiting human skin must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient availability. Yet the skin microbiota thrive on the skin and have adapted to these stressful conditions. The limited nutrients available for microbial use in this unique niche include those from host-derived sweat, sebum, and corneocytes. Here, we have developed physiologically relevant, synthetic skin-like growth media composed of compounds present in sweat and sebum. We find that skin-associated bacterial species exhibit unique growth profiles at different concentrations of artificial sweat and sebum. Most strains evaluated demonstrate a preference for high sweat concentrations, while the sebum preference is highly variable, suggesting that the capacity for sebum utilization may be a driver of the skin microbial community structure. In particular, the prominent skin commensal Staphylococcus epidermidis exhibits the strongest preference for sweat while growing equally well across sebum concentrations. Conversely, the growth of Corynebacterium kefirresidentii, another dominant skin microbiome member, is dependent on increasing concentrations of both sweat and sebum but only when sebum is available, suggesting a lipid requirement of this species. Furthermore, we observe that strains with similar growth profiles in the artificial media cluster by phylum, suggesting that phylogeny is a key factor in sweat and sebum use. Importantly, these findings provide an experimental rationale for why different skin microenvironments harbor distinct microbiome communities. In all, our study further emphasizes the importance of studying microorganisms in an ecologically relevant context, which is critical for our understanding of their physiology, ecology, and function on the skin. The human skin microbiome is adapted to survive and thrive in the harsh environment of the skin, which is low in nutrient availability. To study skin microorganisms in a system that mimics the natural skin environment, we developed and tested a physiologically relevant, synthetic skin-like growth medium that is composed of compounds found in the human skin secretions sweat and sebum. We find that most skin-associated bacterial species tested prefer high concentrations of artificial sweat but that artificial sebum concentration preference varies from species to species, suggesting that sebum utilization may be an important contributor to skin microbiome composition. This study demonstrates the utility of a skin-like growth medium, which can be applied to diverse microbiological systems, and underscores the importance of studying microorganisms in an ecologically relevant context.
Topics: Humans; Sweat; Sebum; Skin; Microbiota; Bacteria
PubMed: 36602383
DOI: 10.1128/spectrum.04180-22 -
Health Science Reports Apr 2022Dark spots, brown spots, or hyperpigmented spots (HPS) are oval or irregular brown areas of skin. Their emergence is associated with dysregulation of the immune system,...
BACKGROUND AND AIMS
Dark spots, brown spots, or hyperpigmented spots (HPS) are oval or irregular brown areas of skin. Their emergence is associated with dysregulation of the immune system, and may also be caused by a deficiency in stromal cell-derived factor-1, leading to perturbed melanogenesis and accumulation of melanosomes within neighboring keratinocytes. The skin microbiota (living microorganisms present on the surface of the skin) is known to play essential roles in maintaining skin homeostasis and in regulating the immune system. Here, we investigated whether the microbiota could play a role in the emergence of HPS.
METHODS
The clinical study involved 38 European women, selected from among 74 volunteers. Participants were divided into two groups depending on the spot areas measured on their faces. The study was designed to avoid conflicting factors: both groups presented similar skin pH, hydration, transepidermal water loss, and sebum levels. The two cohorts were also age-matched, with a mean of 29-years-old for both.
RESULTS
Alpha-diversity of the microbiota was similar for the two groups. On skins with more HPS, seven bacterial genera were identified in significantly higher proportions and included opportunistic pathogens and inflammatory bacteria. Six bacterial genera, including bacteria showing antioxidant and anti-UV properties, were identified in significantly higher proportions on less spotted skins. Cross-domain association networks revealed distinct co-occurrences of genera between the two groups, suggesting nonidentical community structures and exchanges, depending on the HPS status.
CONCLUSION
Our results reveal specific microbiota composition and networks on skins based on HPS status. Changes could alter communication with the immune system, leading to the emergence of dark spots. As an essential part of the overall skin ecosystem, and through its interaction with the skin matrix, the skin microbiota and its maintenance could be considered a new target for skincare applications.
PubMed: 35425869
DOI: 10.1002/hsr2.609 -
BioRxiv : the Preprint Server For... Apr 2024Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with interfollicular epidermis; however, whether...
Our skin provides a protective barrier that shields us from our environment. Barrier function is typically associated with interfollicular epidermis; however, whether hair follicles influence this process remains unclear. Here, we utilize a potent genetic tool to probe barrier function by conditionally ablating a quintessential epidermal barrier gene, , which is mutated in the most severe skin barrier disease, harlequin ichthyosis. With this tool, we deduced 4 ways by which hair follicles modulate skin barrier function. First, the upper hair follicle (uHF) forms a functioning barrier. Second, barrier disruption in the uHF elicits non-cell autonomous responses in the epidermis. Third, deleting in the uHF impairs desquamation and blocks sebum release. Finally, barrier perturbation causes uHF cells to move into the epidermis. Neutralizing Il17a, whose expression is enriched in the uHF, partially alleviated some disease phenotypes. Altogether, our findings implicate hair follicles as multi-faceted regulators of skin barrier function.
PubMed: 38712094
DOI: 10.1101/2024.04.23.590728 -
PeerJ 2023Diseases vary among and within species but the causes of this variation can be unclear. Immune responses are an important driver of disease variation, but mechanisms on... (Review)
Review
Diseases vary among and within species but the causes of this variation can be unclear. Immune responses are an important driver of disease variation, but mechanisms on how the body resists pathogen establishment before activation of immune responses are understudied. Skin surfaces of mammals are the first line of defense against abiotic stressors and pathogens, and skin attributes such as pH, microbiomes, and lipids influence disease outcomes. Sebaceous glands produce sebum composed of multiple types of lipids with species-specific compositions. Sebum affects skin barrier function by contributing to minimizing water loss, supporting thermoregulation, protecting against pathogens, and preventing UV-induced damage. Sebum also affects skin microbiome composition both via its antimicrobial properties, and by providing potential nutrient sources. Intra- and interspecific variation in sebum composition influences skin disease outcomes in humans and domestic mammal species but is not well-characterized in wildlife. We synthesized knowledge on sebum function in mammals in relation to skin diseases and the skin microbiome. We found that sebum composition was described for only 29 live, wild mammalian species. Sebum is important in dermatophilosis, various forms of dermatitis, demodicosis, and potentially white-nose syndrome. Sebum composition likely affects disease susceptibility, as lipid components can have antimicrobial functions against specific pathogens. It is unclear why sebum composition is species-specific, but both phylogeny and environmental effects may drive differences. Our review illustrates the role of mammal sebum function and influence on skin microbes in the context of skin diseases, providing a baseline for future studies to elucidate mechanisms of disease resistance beyond immune responses.
Topics: Humans; Animals; Sebum; Skin Diseases; Mammals; Lipids; Microbiota; Anti-Infective Agents
PubMed: 38144187
DOI: 10.7717/peerj.16680