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The Efficacy Study of Trinity Permeation Synergism on Anti-Aging
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Background
Transient receptor potential vanilloid 1 (TRPV1) is associated with skin sensitivity and mainly activated by capsaicin and heat. Interestingly, troxerutin can inhibit TRPV1 activation. However, its efficacy in reducing skin sensitivity remains undetermined.
Aims
We evaluated the efficacy of troxerutin in alleviating skin sensitivity using clinical tests and in vitro experiments.
Methods
For the in vitro experiment, HaCaT keratinocytes were pretreated with different concentrations of troxerutin, followed by incubation with 50 μM capsaicin for 1, 24, or 48 h. The gene and protein expressions of four inflammatory cytokines involved in skin irritation were determined. Among 35 Korean women with sensitive skin recruited for the clinical trial, 13 were involved in assessing the immediate soothing effects of 0.1% and 0.0095% troxerutin following capsaicin irritation, whereas 22 participated in evaluating the preventive soothing effect of 10% and 1% troxerutin over 4 weeks against capsaicin‐ and heat‐induced irritation. We evaluated the soothing rate using skin redness, visual analog scale, and high temperature sensitive index as evaluation indices.
Results
Troxerutin inhibited the mRNA and protein expressions of cytokines in capsaicin‐treated keratinocytes. In the clinical study, 0.1% and 0.0095% troxerutin promptly alleviated capsaicin‐induced skin redness, whereas 10% troxerutin notably decreased both the visual analog scale and high temperature sensitive index for capsaicin‐ and heat‐related irritation. However, 1% troxerutin was only effective in reducing the visual analog scale in response to capsaicin irritation.
Conclusions
Troxerutin can inhibit TRPV1 activation in clinical and in vitro tests.
Background
Home beauty devices for facial rejuvenation utilizing technologies such as radiofrequency, microcurrent, and light emitting diode have gained widespread attention due to their claimed ability to improve skin tightness and elasticity, making them popular among consumers. However, there is controversy within the industry regarding the effectiveness and safety of these devices.
Objective
This study aims to verify the safety and effectiveness of these home beauty devices in treating skin aging based on relevant efficacy evaluation indicators.
Methods
A systematic search of PubMed and web of science was conducted to include original research literature on the efficacy of home beauty devices for facial rejuvenation over the past two decades. The selected literature was processed and analyzed based on efficacy evaluation indicators such as sample size, follow-up period, experimental results, adverse reactions, and others.
Results
After screening, a total of 18 clinical studies were included. A comprehensive analysis of the experimental results and adverse reaction indicators from existing literature revealed that home beauty devices for facial rejuvenation can improve skin aging to a certain extent. Apart from transient redness and swelling, no other adverse reactions were observed.
Conclusion
Despite the variety of home beauty devices for facial rejuvenation available in the market, corresponding research reports are limited. Existing studies suffer from issues such as small sample sizes and short follow-up periods, highlighting the need for a more comprehensive efficacy evaluation system. Furthermore, the physical stimulation of meridian acupoints by home beauty devices for facial rejuvenation may meet the multi-dimensional anti-aging needs of patients, suggesting a potential direction for future research.
Skin ageing is a complex process involving the additive effects of skin’s interaction with its external environment, predominantly chronic sun exposure, upon a background of time-dependent intrinsic ageing. Skin health and beauty is considered one of the principal factors perceived to represent overall ‘health and wellbeing’; thus, the demand for skin rejuvenation strategies has rapidly increased, with a worldwide annual expenditure expected to grow from US44.5 billion by 2030 (https://www.databridgemarketresearch.com/reports/global-facial-rejuvenation-market). Skin rejuvenation can be achieved in several ways, ranging from laser and device-based treatments to chemical peels and injectables; however, topical skin care regimes are a mainstay treatment for ageing skin and all patients seeking skin rejuvenation can benefit from this relatively low-risk intervention. While the most efficacious topical rejuvenation treatment is application of tretinoin (all-trans retinoic acid) – a prescription-only medicine considered to be the clinical ‘gold standard’ – a hybrid category of ‘cosmeceutical’ products at the midpoint of the spectrum of cosmetics and pharmaceutical has emerged. This article reviews the clinical manifestations of skin ageing and the available topical treatments for skin rejuvenation, including retinoids, peptides and antioxidants.
Ergothioneine, Ovothiol and Selenoneine are sulfur/selenium-containing histidine-derived natural products widely distributed across different organisms. They exhibit significant antioxidant properties, making them as potential lead compounds for promoting health. Increasing evidence suggests that Ergothioneine is positively correlated with healthy ageing and longevity. The mechanisms underlying Ergothioneine regulation of the ageing process at cellular and molecular level are beginning to be understood. In this review, we provide an in-depth and extensive coverage of the anti-ageing studies on Ergothioneine and discuss its possible intracellular targeting pathways. In addition, we highlight the recent efforts in elucidating the biosynthetic details for Ergothioneine, Ovothiol and Selenoneine, with a particular focus on the study of their pharmacophore-forming enzymology.
Bioactive peptides have gained significant attention in the cosmetic industry due to their potential in enhancing skin health and beauty. These small protein fragments exhibit various biological activities, such as antioxidant, anti-aging, anti-inflammatory, and antimicrobial activities, making them ideal ingredients for cosmetic formulations. These bioactive peptides are classified into four categories: signal, carrier, neurotransmitter-inhibitory, and enzyme-inhibitory peptides. This review provides insight into applying bioactive peptides in cosmetics and their mechanisms of action (e.g., downregulating pro-inflammatory cytokines, radical scavenging, inhibiting collagen, tyrosinase, and elastase synthesis). The abundant natural origins (e.g., animals, plants, and marine sources) have been identified as primary sources for extractions of cosmetic peptides through various techniques (e.g., enzymatic hydrolysis, ultrafiltration, fermentation, and high-performance liquid chromatography). Furthermore, the safety and regulatory aspects of using peptides in cosmetics are examined, including potential allergic reactions and regulatory guidelines. Finally, the challenges of peptides in cosmetics are discussed, emphasizing the need for further research to fully harness their potential in enhancing skin health. Overall, this review provides a comprehensive understanding of the application of peptides in cosmetics, shedding light on their transformative role in developing innovative and effective skincare products.
The skin is the human body's largest organ, and serves as a crucial boundary between the body and the external environment. As a natural process, skin aging cannot be avoided, and it causes changes in the skin's strength, structure, elasticity, and integrity. Many approaches have been developed over the years for studying the skin, including in vivo and in vitro methods. Nevertheless, animal assays have ethical and lack of reproducibility issues. Hence, in vitro skin models have been increasingly developed and used. For the assessment of the potential of the anti-aging activity of compounds of different origins, the most commonly used in vitro assays are the ones evaluating antioxidant, anti-collagenase, anti-elastase, anti-hyaluronidase, anti-tyrosinase, anti-inflammatory, antiglycation or moisturizing activity, and induction of skin cell proliferation/anti-senescence effects or inhibition of matrix metalloproteinases production. The purpose of this review is to summarize the most commonly used in vitro models for the evaluation of skin aging and cosmetic product’s anti-aging efficacy, providing a useful guide for researchers in the field. Overall, these assays provide important data on the safety and efficacy of anti-aging compounds, and a foundation for research and eventual introduction of formulations into the cosmetics market.
Background:
Regenerative aesthetics (RA) is an emerging subfield based on many of the principles of regenerative medicine (RM). In order to ensure that the development of regenerative aesthetics is based on accepted regenerative concepts and to optimize treatment strategies, it is important to establish clear definitions, fundamental aims and consider the impact of the predominant RA tissue environment RM focuses on the regeneration of injured or diseased tissue, while RA aims to restore youthful properties to aging, senescent tissue. The distinction is key in understanding how best to develop treatments for these different goals.
Aims and methods:
The current review suggests key concepts, definitions, and foundations of regenerative aesthetic approaches and examines current evidence supporting this. It considers the importance of the aging tissue environment, the essential regenerative goals of restored tissue structure and function and introduces the concept of regenerative scaffolds with a focus on CaHA. Current techniques in the field and promising future directions are also discussed.
Conclusion:
Regenerative aesthetics is an evolving subfield of regenerative medicine. Establishing clear definitions, identifying the challenges of the aging soft tissue environment and re-evaluating current evidence in light of regenerative goals are vital for the continuing evolution of this medical field.
Ergothioneine, a sulfur-containing micromolecular histidine derivative, has attracted increasing attention from scholars since it was confirmed in the human body. In the human body, ergothioneine is transported and accumulated specifically through OCTN-1, especially in the mitochondria and nucleus, suggesting that it can target damaged cells and tissues as an antioxidant. It shows excellent antioxidant, anti-inflammatory effects, and anti-aging properties, and inhibits melanin production. It is a mega antioxidant that may participate in the antioxidant network system and promote the reducing glutathione regeneration cycle. This review summarizes studies on the antioxidant effects of ergothioneine on various free radicals in vitro to date and systematically introduces its biological activities and potential mechanisms, mostly in dermatology. Additionally, the application of ergothioneine in cosmetics is briefly summarized. Lastly, we propose some problems that require solutions to understand the mechanism of action of ergothioneine. We believe that ergothioneine has good prospects in the food and cosmetics industries, and can thus meet some needs of the health and beauty industry.
Introduction
Although skin color has been suggested to be associated with the risk of some chronic disease, there has been no validated visual skin‐color scale, with which subjects can self‐report their skin color. Our objective was to develop a visual skin color evaluation scale for self‐reporting that would be useful in large‐scale epidemiological studies.
Materials and methods
Study participants were 99 university Japanese students aged 19–29. We developed a skin color evaluation scale consisting of six colors from light to dark. Participants were asked to choose one color that was the closest to their skin color. Their skin color was measured on the back of the hand and the inner upper arm by an examiner using a narrowband reflective spectrophotometer. Self‐reported skin color was compared with the melanin and erythema indices.
Results
Spearman's rank correlation coefficients of self‐reported color with the melanin index after adjusted for age, temperature, and humidity were moderate but significant at both sites for both men and women. The correlation coefficients with the erythema index were significant only on the back of the hand for men. The higher melanin index was significantly associated with the darker skin color in both sexes for both sites. The erythema index showed such a significant trend only in men and not in women.
Conclusions
The validity of the skin color chart was moderate of melanin among Japanese people. It may be useful for large population studies examining the relationships between skin color and health outcomes.
Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.
This paper presents a numerical comparison of viscoelastic shear-thinning fluid flow using a generalized Oldroyd-B model and Johnson–Segalman model under various settings. Results for the standard shear-thinning generalization of Oldroyd-B model are used as a reference for comparison with those obtained for the same flow cases using Johnson–Segalman model that has specific adjustment of convected derivative to assure shear-thinning behavior. The modeling strategy is first briefly described, pointing out the main differences between the generalized Oldroyd-B model (using the Cross model for shear-thinning viscosity) and the Johnson–Segalman model operating in shear-thinning regime. Then, both models are used for blood flow simulation in an idealized stenosed axisymmetric vessel under different flow rates for various model parameters. The simulations are performed using an in-house numerical code based on finite-volume discretization. The obtained results are mutually compared and discussed in detail, focusing on the qualitative assessment of the most distinct flow field differences. It is shown that despite all models sharing the same asymptotic viscosities, the behavior of the Johnson–Segalman model can be (depending on flow regime) quite different from the predictions of the generalized Oldroyd-B model.
Chemical compositions, antioxidants, and anti-aging activities of Cortex Moutan (CM), from different collection periods and different producing areas, were measured and compared in order to obtain excellent CM extracts. The bioactivities of CM extracts were examined by an in vitro antioxidant method and a UVB irradiated human dermal fibroblast (HDF) model. Phytochemical properties were obtained from ultra-fast liquid chromatography quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF-MS) prior to the multivariate statistical analysis. As for the results, the extracts of Heze CM (HZCM) and Luoyang CM (LYCM) collected in June had better in vitro antioxidant activities, significantly increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the content of malondialdehyde (MDA), compared to other CM extracts. HZCM and LYCM extracts could upregulate the relative expression of SOD and GSH-Px mRNA. The extract of HZCM collected in June could significantly repress the production of matrix metalloproteinase 1 (MMP-1) and improve the production of procollagen type I (PCOL)-I in UVB irradiated HDF. In total, 50 compounds, including 17 monoterpenoids, 19 flavonoids, 13 phenols, and 1 amino acid were identified or tentatively identified in the CM extracts. Gallic acid, p-hydroxybenzoic acid, oxypaeoniflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloyl glucose, and paeonol were predominant compounds in the CM extracts. Taken together, CM collected from April to September had better antioxidant and anti-aging effects for external usage.
Background: The interest in maintaining a young and attractive appearance in an era with increasingly hectic rhythms has generated a pressing demand for effective aesthetic procedures with the shortest possible recovery period, stimulating the search for non-invasive, yet successful, solutions. The aim of this study was to evaluate the effectiveness of the combined soft peeling and MN technique on the various imperfections typical of facial aging. Methods: This multicentric uncontrolled experimental study recruited a population of healthy subjects of both sexes with advanced signs of photo- and chrono-aging. These subjects were provided with a single session of microneedling and peeling at the same time. Recruited subjects were re-evaluated 30 (±4) and 60 (±4) days after treatment by photographic comparison before and after treatment. The physicians evaluated the improvement of facial wrinkles according to the Wrinkle Assessment Scale of Lemperle. Forty-nine subjects completed the study and showed a significant improvement in wrinkles in all areas of the face. Results: There were no significant differences in the different subpopulations compared: males–females, Glogau 3–Glogau 4, smokers–non-smokers, phototypes 1–4, and check up at 30 days–control at 60 days. The adverse events manifested were localized edema in four cases (8.2%) lasting an average of 3–4 days, very fine crustiness in four cases (8.2%), transient post inflammatory dyschromia in two cases (4.1%) lasting 2–3 weeks, and herpetic reactivation in one case (2.0%). Conclusions: The study demonstrates the therapeutic efficacy of the combined needling-peeling treatment in different types of wrinkles.
The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and protect the skin from adverse effects of ultraviolet radiation (UVR) and oxidative stress from various environmental pollutants. Melanocytes reside in the basal layer of the interfollicular epidermis and are compensated by melanocyte stem cells in the follicular bulge area. Various stimuli such as eczema, microbial infection, ultraviolet light exposure, mechanical injury, and aging provoke skin inflammation. These acute or chronic inflammatory responses cause inflammatory cytokine production from epidermal keratinocytes as well as dermal fibroblasts and other cells, which in turn stimulate melanocytes, often resulting in skin pigmentation. It is confirmed by some recent studies that several interleukins (ILs) and other inflammatory mediators modulate the proliferation and differentiation of human epidermal melanocytes and also promote or inhibit expression of melanogenesis-related gene expression directly or indirectly, thereby participating in regulation of skin pigmentation. Understanding of mechanisms of skin pigmentation due to inflammation helps to elucidate the relationship between inflammation and skin pigmentation regulation and can guide development of new therapeutic pathways for treating pigmented dermatosis. This review covers the mechanistic aspects of skin pigmentation caused by inflammation.
Background:
Photoaging, ultra violet (UV) induced skin aging is a gradual process that depends on the time and intensity of solar radiation.
Aim:
The aim of this paper was to review of the literature focused on in vitro studies explaining the mechanisms of photoaging.
Methods:
Electronic databases, including PubMed and MEDLINE, were searched for in vitro studies on the importance of UV radiation in the skin photoaging process of peer-reviewed scientific journals. Only articles available in English and full version publications were considered for this review.
Results:
Three main modes of UV radiation action on skin cells which lead to photoaging, there are changes in cell metabolism, induction of oxidative stress due to the change in enzyme activity.
Conclusion:
The information gathered in this publication will help to better understand the complex and multidirectional mechanism of skin photoaging, which will contribute to the development of research in the search for potential cosmetic products that provide effective and safe sun protection or repair damage caused by UV radiation.
The development of synthetic peptides for skin care dates to the 1980s. The cosmetic industry periodically launches new peptides, as they are promising and appealing active ingredients in the growing and innovative cosmetics market. In this study, trends in the use of peptides in anti-aging products were analyzed by comparing the composition of the products marketed in 2011 with products launched or reformulated in 2018. The scientific and marketing evidence for their application as active ingredients in anti-aging cosmetics was also compiled from products’ labels, suppliers’ technical data forms and online scientific databases. The use of peptides in anti-aging cosmetics increased by 7.2%, while the variety and the number of peptide combinations in products have increased by 88.5%. The most used peptides in antiaging cosmetic formulations are, in descending order, Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide and Acetyl Hexapeptide-8. In 2011, the majority of peptides were obtained from synthesis, while in 2018, biotechnology processing was the dominant source. This study provides an overview of the market trends regarding the use of peptides in anti-aging products, providing meaningful data for scientists involved in the development of new peptides to identify opportunities for innovation in this area.
In this article, a new relationship between viscosity and molecular diffusion at infinite dilution is proposed for better rationalization and prediction of these properties, based on a “macroscopic viscosity approximation” (MVA), i.e., by assuming viscosity around a solute as equal to the macroscopic, measurable viscosity of the solvent. This implies that activation energies of the viscous flow and diffusion process are equal. The hypothesis is validated by our correlation analysis (mean difference of 0.10 kcal/mol, R2 = 0.96). The new approach, named “Modified Stokes–Einstein” (MSE), achieves better performance than the widely used Wilke–Chang (WC) correlation both in organic solvents [mean relative error (MRE) of 15% vs 24%, respectively] and in water (MRE of 13% vs 21%, respectively). Contrary to the popular WC correlation as well as all other available approaches in the literature, the MSE approach can be used consistently for water, without requiring any ad hoc association parameter, and is not fitted on diffusion and/or viscosity data, making all of its underlying hypotheses explicit. Based on the MVA and the MSE, a simple atomic count estimation method for the activation energy of the flow allows us to simultaneously predict viscosity and diffusion coefficients with an MRE of 21%–22%, again slightly better than the WC correlation, but not requiring any experimental data as the input. This work provides rationalized and efficient means for prediction of diffusion coefficients at infinite dilution and pure liquid viscosities wherever such properties are required, for example, as inputs for mixing rules to predict flow and transport behavior of complex systems.
Tissue homeostasis depends on a balance of synthesis and degradation of constituent proteins, with turnover of a given protein potentially regulated by its use. Extracellular matrix (ECM) is predominantly composed of fibrillar collagens that exhibit tension-sensitive degradation, which we review here at different levels of hierarchy. Past experiments and recent proteomics measurements together suggest that mechanical strain stabilizes collagen against enzymatic degradation at the scale of tissues and fibrils whereas isolated collagen molecules exhibit a biphasic behavior that depends on load magnitude. Within a Michaelis-Menten framework, collagenases at constant concentration effectively exhibit a low activity on substrate fibrils when the fibrils are strained by tension. Mechanisms of such mechanosensitive regulation are surveyed together with relevant interactions of collagen fibrils with cells.
Solamargine, an active ingredient of Solanum nigrum, has been previously revealed to inhibit the proliferation of cancer cells. However, the effect of solamargine on human cholangiocarcinoma cells and the underlying molecular mechanism remain unknown. In the present study, the molecular mechanism underlying the anti-cancer effect of solamargine was assessed in human cholangiocarcinoma QBC939 cells. The results of the present study revealed that solamargine inhibited the viability of QBC939 cells in a dose-dependent manner. Furthermore, solamargine significantly induced the apoptosis of QBC939 cells and altered the mitochondrial membrane potential of cells. Quantitative polymerase chain reaction analysis revealed that solamargine decreased the mRNA level of B-cell lymphoma-2 (Bcl-2), Bcl-extra-large and X-linked inhibitor of apoptosis protein but increased the mRNA level of Bcl-2-associated X protein (Bax). In addition, western blot analysis demonstrated that solamargine inhibited the protein expression of Bcl-2 and poly ADP ribose polymerase (PARP), and promoted the protein expression of Bax, cleaved PARP, caspase 3, cleaved caspase 3 and caspase 7. Therefore, the results of the present study revealed that solamargine may induce apoptosis via the mitochondrial pathway and alter the level of apoptosis-associated proteins in human cholangiocarcinoma QBC939 cells. This in vitro study demonstrated that solamargine may be an effective chemotherapeutic agent against cholangiocarcinoma in clinical practice.
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel present on sensory neurons which is activated by heat, protons, capsaicin and a variety of endogenous lipids termed endovanilloids. As such, TRPV1 serves as a multimodal sensor of noxious stimuli which could trigger counteractive measures to avoid pain and injury. Activation of TRPV1 has been linked to chronic inflammatory pain conditions and peripheral neuropathy, as observed in diabetes. Expression of TRPV1 is also observed in non-neuronal sites such as the epithelium of bladder and lungs and in hair cells of the cochlea. At these sites, activation of TRPV1 has been implicated in the pathophysiology of diseases such as cystitis, asthma and hearing loss. Therefore, drugs which could modulate TRPV1 channel activity could be useful for the treatment of conditions ranging from chronic pain to hearing loss. This review describes the roles of TRPV1 in the normal physiology and pathophysiology of selected organs of the body and highlights how drugs targeting this channel could be important clinically.
Abstract There is a concern that peptides in cosmetic creams marketed as anti-aging/anti-wrinkle may penetrate into the deep layers of the skin and potentially stimulate biological activity. Claims for one cosmetic peptide, acetyl hexapeptide-8 (Ac-EEMQRR-amide), suggest interference with neuromuscular signaling as its anti-wrinkle mechanism of action. Therefore, the skin penetration of commercially available Ac-EEMQRR-amide from a cosmetic formulation (oil-in-water (O/W) emulsion) was determined in hairless guinea pig (HGP) and human cadaver skin assembled into in vitro diffusion cells. An O/W emulsion containing 10% Ac-EEMQRR-amide was applied to skin at a dose of 2 mg/cm(2). After a 24-h exposure, the skin surface was washed to remove unabsorbed peptide. Skin disks were tape stripped to determine the amount of peptide in the stratum corneum. Removal of the stratum corneum layers was verified by confocal microscopy. The epidermis was heat separated from the dermis and each skin fraction was homogenized. Skin penetration of Ac-EEMQRR-amide was measured in skin layers by hydrophilic interaction liquid chromatography with tandem mass spectrometry using electrospray ionization (ESI) in the positive mode. Stable isotopically labeled hexapeptides were used as internal standards for the quantitation of native hexapeptides to correct for matrix effects associated with ESI. The results (percent of applied dose) showed that the majority of the Ac-EEMQRR-amide was washed from the surface of both HGP and human skin. Ac-EEMQRR-amide that penetrated skin remained mostly in the stratum corneum of HGP (0.54%) and human (0.22%) with the peptide levels decreasing as each layer was removed by tape stripping. Total Ac-EEMQRR-amide found in the epidermis of HGP and human skin was similar at 0.01%. No peptide was detected in the dermis or buffer collected underneath the skin for both human and HGP. There was no hexapeptide metabolite (H2N-EEMQRR-amide) detected in any layers of HGP skin, human skin or buffer collected underneath the skin. This skin penetration data will be useful for evaluating the safety of cosmetic products containing small peptide cosmetic ingredients.
Maintaining optimal mitochondrial function is a feature of health. Mitophagy removes and recycles damaged mitochondria and regulates the biogenesis of new, fully functional ones preserving healthy mitochondrial functions and activities. Preclinical and clinical studies have shown that impaired mitophagy negatively affects cellular health and contributes to age-related chronic diseases. Strategies to boost mitophagy have been successfully tested in model organisms, and, recently, some have been translated into clinics. In this Review, we describe the basic mechanisms of mitophagy and how mitophagy can be assessed in human blood, the immune system and tissues, including muscle, brain and liver. We outline mitophagy's role in specific diseases and describe mitophagy-activating approaches successfully tested in humans, including exercise and nutritional and pharmacological interventions. We describe how mitophagy is connected to other features of ageing through general mechanisms such as inflammation and oxidative stress and forecast how strengthening research on mitophagy and mitophagy interventions may strongly support human health.
Background:
Skin aging is a complex multifactorial progressive process. With age, intrinsic and extrinsic factors cause the loss of skin elasticity, with the formation of wrinkles, resulting in skin sagging through various pathways. A combination of multiple bioactive peptides could be used as a treatment for skin wrinkles and sagging.
Objectives:
This study aimed to evaluate the cosmetic efficacy of a multi-peptide eye serum as a daily skin-care product for improving the periocular skin of women within the ages of 20-45 years.
Methods:
The stratum corneum skin hydration and skin elasticity were assessed using a Corneometer CM825 and Skin Elastometer MPA580, respectively. The PRIMOS CR technique based on digital strip projection technology was used for skin image and wrinkle analysis around the "crow's feet" area. Self-assessment questionnaires were filled on Day 14 and 28 of product use.
Results:
This study included 32 subjects with an average age of 28.5 years. On Day 28, there was a significant decrease in the number, depth, and volume of wrinkles. Skin hydration, elasticity, and firmness increased continuously during the study period, consistent with typical anti-aging claims. A majority of the participants (75.00%) expressed overall satisfaction with their skin appearance after using the product. Most participants noted a visible skin improvement, with an increase in skin elasticity and smoothness, and confirmed the extensibility, applicability, and temperance of the product. No adverse reactions related to product use were observed.
Conclusions:
The multi-peptide eye serum uses a multi-targeted mechanism against skin aging to improve the skin appearance, making it an ideal choice for daily skincare.
As the world emerges from the COVID-19 pandemic, prices for various goods and services, including cosmetic surgery, remain in flux. Specifically, those surgeons performing aesthetic surgery continue to establish prices for various surgeries as well as minimally invasive procedures with neurotoxins and fillers. It would clearly be beneficial not only to know national average pricing available via The Aesthetic Society's 2021 National Databank Statistics, but also within the region in which one practices. The Special Topic article entitled “The Price Is Right? An Economic Analysis of Factors Influencing Cosmetic Surgery Prices” provides an in-depth, robust analysis identifying “variables that have the greatest impact on price determination.”1,2 The information gleaned from this unique perspective facilitates what price to charge to maximize the revenue of one's cosmetic practice.
The authors’ first aim was to compare publicly reported prices to national averages, including the specific variables that profoundly impact price determination. To do this, they performed an internet search—after “clearing all browsing data” to avoid location bias—and generated a random list of practices that publicly reported cosmetic surgery prices. These data were compared with the national prices from the aforementioned finding that publicly reported prices were significantly higher for almost all breast, body, and facial surgical procedures. In contrast, neurotoxin and fillers were significantly lower than publicly reported prices.
Hyaluronic acid (HA) has been widely used in cosmetics and topical preparations owing to its favorable moisturizing property and potential in enhancing drugs' skin permeability. Here, the influencing factors and underlying mechanism of HA on skin penetration were carefully investigated, and HA-modified Undecylenoyl-Phenylalanine (UP) liposomes (HA-UP-LPs) were designed as a proof of principle for efficacious transdermal drug delivery strategy to enhance the skin penetration and retention. An in vitro penetration test (IVPT) of HA with different molecular weights showed that low molecular weight HA (LMW-HA, 5 kDa and 8 kDa) could pass through the stratum corneum (SC) barrier and enter into the epidermis and dermis layers, whereas its high molecular counterparts (HMW-HA) were trapped on the SC surface. Mechanistic studies revealed that LMW-HA could interact with keratin and lipid in the SC meanwhile exerted a substantial skin hydration effect, which may partially contribute to the SC penetration benefit. In addition, the surface decoration of HA drove an energy-dependent caveolae/lipid raft-mediated endocytosis of the liposomes through direct binding to the CD44 receptors widely expressed on skin cell membranes. Notably, IVPT showed a 1.36-fold and 4.86-fold increase in skin retention of UP and a 1.62-fold and 5.41-fold increase in skin penetration of UP with HA-UP-LPs over UP-LPs and free UP at 24 h, respectively. As a result, the anionic HA-UP-LPs (-30.0 mV) showed enhanced drug skin penetration and retention compared with conventional cationic bared UP-LPs (+21.3 mV) on both in vitro mini-pig skin as well as in vivo mouse skin. Overall, the usage of LMW-HA might offer opportunities in developing novel topical preparations and skin care products with improved transdermal penetration and retention.
Objective:
Skin fibrosis places an enormous burden on patients and society, but disagreement exists over methods to quantify severity of skin scarring. A suction cutometer measures skin elasticity in-vivo, but it has not been widely adopted due to inconsistency in data produced. We investigated variability of several dimensionless parameters generated by the cutometer to improve their precision and accuracy.
Approach:
Twenty adult human subjects underwent suction cutometer measurement of normal skin and fibrotic scars. Using Mode 1, each subject underwent 5 trials with each trial containing 4 curves. R0/2/5/6/7 and Q1/2/3 data were collected. Analyses were performed on these calculated parameters.
Results:
R0/2/5/6/7 and Q1/2 parameters from curves 1-4 demonstrated significant differences, while these same parameters were not significantly different when only using curves 2-4. Individual analysis of all parameters between curve 1 and every subsequent curve was statistically significant for R0, R2, R5, R6, R7, Q1, and Q2. No differences were appreciated for parameter Q3. Comparison between normal skin and fibrotic scars were significantly different for parameters R5, Q1, and Q3.
Innovation:
Our study is the first demonstration of accurate comparison between normal skin and fibrotic scars using the dimensionless parameters of a suction cutometer.
Conclusion:
Measured parameters from the first curve of each trial were significantly different from subsequent curves for both normal skin and fibrotic scars. Precision and reproducibility of data from dimensionless parameters can therefore be improved by removing the first curve. R5, Q1, and Q3 parameters differentiated normal skin as more elastic than fibrotic scars.
Cells have the ability to respond to various types of environmental cues, and in many cases these cues induce directed cell migration towards or away from these signals. How cells sense these cues and how they transmit that information to the cytoskeletal machinery governing cell translocation is one of the oldest and most challenging problems in biology. Chemotaxis, or migration towards diffusible chemical cues, has been studied for more than a century, but information is just now beginning to emerge about how cells respond to other cues, such as substrate-associated cues during haptotaxis (chemical cues on the surface), durotaxis (mechanical substrate compliance) and topotaxis (geometric features of substrate). Here we propose four common principles, or pillars, that underlie all forms of directed migration. First, a signal must be generated, a process that in physiological environments is much more nuanced than early studies suggested. Second, the signal must be sensed, sometimes by cell surface receptors, but also in ways that are not entirely clear, such as in the case of mechanical cues. Third, the signal has to be transmitted from the sensing modules to the machinery that executes the actual movement, a step that often requires amplification. Fourth, the signal has to be converted into the application of asymmetric force relative to the substrate, which involves mostly the cytoskeleton, but perhaps other players as well. Use of these four pillars has allowed us to compare some of the similarities between different types of directed migration, but also to highlight the remarkable diversity in the mechanisms that cells use to respond to different cues provided by their environment.
Background:
Monitoring the effects of biologic therapies in skin diseases will benefit from alternative nonivasive skin sampling techniques to examine immune pathways in diseased tissue early and longitudinally.
Objective:
To establish minimally invasive profiling of skin cytokines for diagnosis, therapeutic response monitoring and clinical research in atopic dermatitis (AD) and other skin diseases, particularly in pediatric cohorts.
Methods:
We developed a novel method for cytokine profiling in the epidermis using skin tape strips (STS) in a setting designed to maximize the efficiency of protein extraction from STS. This method was applied to analyze STS protein extracts from lesional skin of AD children (n=41) and normal healthy controls (n=22). Twenty cytokines were probed with ultra sensitive Mesoscale multiplex cytokine assay.
Results:
A significant increase in IL-1b, IL-18, IL-8 and a decrease in IL-1a in the stratum corneum of AD lesional skin was found. Concurrently, an increase in markers associated with type 2 inflammatory response was readily detectable in AD lesional skin, including CCL22, CCL17 and TSLP. Levels of IL-1b, IL-18 and TSLP exhibited positive correlations with AD severity index (SCORAD) and skin transepidermal water loss (TEWL), while an inverse correlation between IL-1a and SCORAD, IL-1a and TEWL was found. Levels of CCL17, CCL22, TSLP, IL-22 and IL-17a correlated with skin TEWL measurements.
Conclusion:
Using minimally invasive STS analysis we identified cytokine profiles easily sampled in AD lesional skin. The expression of these markers correlated with disease severity and reflected changes in TEWL in lesional skin. These markers suggest new response assessment targets for AD skin.
The present study investigated the transdermal delivery of donepezil hydrochloride across dermatomed porcine ear skin using passive and physical enhancement techniques. In vitro permeation studies were performed on Franz diffusion cells. Microneedles were fabricated in the lab using a polymeric blend of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP). The fabricated microneedles were characterized using SEM. Effect of PVA-PVP microneedles and ablative laser (P.L.E.A.S.E) alone, and in combination with anodal iontophoresis on the delivery of donepezil hydrochloride was investigated. Scanning electron microscopy, histology, methylene blue staining, and confocal laser microscopy were used to characterize the microchannels created in the skin. Permeation of donepezil after passive delivery was found to be 26.87 ± 3.97 µg/sq.cm. Microneedles, laser, and iontophoresis significantly increased the permeation to 282.23 ± 8.28 µg/sq.cm, 1562 ± 231.8 µg/sq.cm and 623.4 ± 21.3 µg/sq.cm. Also, a significantly higher permeation was achieved with microneedles and laser in combination with iontophoresis (1000 ± 160.9 µg/sq.cm and 1700.4 ± 189.43 µg/sq.cm respectively). A sharp increase in flux was observed with a combination of skin microporation and iontophoresis, however, the same was not observed for iontophoretic delivery alone. Thus, flux can be successfully tailored with a combination of skin microporation and iontophoresis to suit patient needs.
Introduction: Ultraviolet radiation induces skin photoaging by increasing matrix metalloproteinase-1 (MMP-1). MMP-1 degrades type I and III collagen that comprise the dermal connective tissue. Achatina fulica mucous (AFM) is a natural remedy that has protective effects on fibroblasts and collagen. Objective: To investigate the effects of AFM on cell viability and collagen deposition in UVB-irradiated human fibroblast culture. Methods: The mucous was extracted from 50 Achatina fulica snails that were stimulated by a 5-10 Volt electricity shock for 30-60 seconds and converted into powder by the freeze-drying process. The human dermal fibroblast culture was divided into six groups: group 1 were normal fibroblasts without UVB irradiation as normal control, groups 2-5 consisted of 100 mJ/cm2 UVB-irradiated fibroblasts. Group 2 had no treatment as negative control, group 3 was treated by PRP 10% as positive control group and groups 4-6 were treated by various concentrations of AFM (3.9; 15.625 and 62.5 μg/mL). At the end of the experiment, the proliferation was assessed with MTT assay, furthermore collagen deposition was measured by Sirius red assay. Real Time-PCR (RT-PCR) was performed to quantify Coll I, Coll III and MMP-1 mRNA expression, then to measured COL 1/COL III ratio. Results: UVB induced significant lower viability, upregulated MMP-1 and downregulated COL I and COL III mRNA expressions. Meanwhile AFM treated groups demonstrated higher cell viability with downregulation of MMP-1 and upregulation of COL I and COL III mRNA expressions. The ratio of COL I/ III expression was significantly (p<0.05) lower in the AFM treated groups compared to the UVB group. Among AFM treated groups, administration of 62.5 μg/mL AFM represented the best result. Conclusion: AFM may ameliorate viability of UVB-irradiated human fibroblast culture which associates with downregulating MMP-1, upregulating COL I and Col III, and reducing COL I/III ratio.
Minimally invasive procedures including neurotoxins, dermal fillers, deoxycholic acid, lasers, peels, and microneedling offer powerful, less permanent adjuncts to surgery that are highly effective in select patients. Injectables and skin resurfacing techniques target facial irregularities including wrinkles and fine lines, decrease in volume and contour, and unwanted fat. Determining the best approach for a given patient involves careful consideration of the patient's health conditions, unique anatomic characteristics, tissue quality, and desired results. A detailed understanding of facial anatomy, aesthetics, and techniques is necessary to master these approaches. This article addresses the spectrum of nonsurgical cosmetic procedures to rejuvenate and optimize the face.
The skin provides the primary protection for the body against external injuries and is essential in the maintenance of general homeostasis. During ageing, resident cells become senescent and the extracellular matrix, mainly in the dermis, is progressively damaged affecting the normal organization of the skin and its capacity for repair. In parallel, extrinsic factors such as ultraviolet irradiation, pollution, and intrinsic factors such as diabetes or vascular disease can further accelerate this phenomenon. Indeed, numerous mechanisms are involved in age-induced degradation of the skin and these also relate to non-healing or chronic wounds in the elderly. In particular, the generation of reactive oxygen species seems to play a major role in age-related skin modifications. Certainly, targeting both the hormonal status of the skin or its surface nutrition can slow down age-induced degradation of the skin and improve healing of skin damage in the elderly. Skin care regimens that prevent radiation and pollution damage, and reinforce the skin surface and its microbiota are among the different approaches able to minimize the effects of ageing on the skin.
Background
Aesthetic procedures are among the most common surgeries performed by plastic surgeons. The prevalence of persistent pain remains unknown and underappreciated in the plastic surgery literature.
Objectives
The purpose of this article was to increase awareness of this problem while describing the diagnostic and management strategies for patients with postoperative pain after aesthetic plastic surgery.
Methods
A literature review of was performed using the PubMed database to identify painful complications of: brachioplasty, blepharoplasty, rhytidectomy, abdominoplasty, breast augmentation, mastopexy, and breast reduction. A treatment algorithm was described to guide plastic surgeons presented with patients reporting pain after aesthetic surgery.
Results
Title and abstract review followed by application of inclusion and exclusion criteria finally resulted in a total of 20 clinical studies that were included in this review. These included: lateral femoral cutaneous nerve, iliohypogastric nerve, and intercostal nerves after Abdominoplasty; median antebrachial cutaneous nerve after brachioplasty; supraorbital, supratrochlear and infratrochlear nerves after blepharoplasty; greater auricular nerve, auriculotemporal nerve, and zygomaticofacial nerve after rhytidectomy; intercostobrachial nerve after breast surgery.
Conclusions
Neuromas can be the source of pain following aesthetic surgery. The same clinical and diagnostic approach used for upper and lower extremity neuroma pain can be used in patients with persistent pain after aesthetic surgery.
Schisandrin B (Sch B), an active extract of Schisandra chinensis, has demonstrated antioxidant activity in a number of in vitro and in vivo models. In the present study, the capacity of Sch B to protect against oxidative injury in keratinocytes using the human keratinocyte‑derived HaCaT cell line was investigated. To induce oxidative injury, tert‑Butyl hydroperoxide (tBHP) was employed. The results indicate that Sch B efficiently reduced tBHP‑induced cell death, reactive oxygen species (ROS) generation, protein oxidation, lipid peroxidation and DNA damage. Sch B also effectively attenuated the loss of mitochondrial membrane potential (MMP), and restored adenosine triphosphate (ATP) levels in tBHP‑injured HaCaT cells. Furthermore, Sch B enhanced the expression of key antioxidant enzymes, including catalase, heme oxygenase‑1, glutathione peroxidase, and superoxide dismutase, and further engaged the nuclear factor‑erythroid 2‑related factor 2 (Nrf2) signaling pathway by modulating its phosphorylation through activating multiple upstream kinases, including protein kinase B, adenosine monophosphate‑activated protein kinase and mitogen‑activated protein kinases (MAPKs). The present study suggests that Sch B provides a protective effect in keratinocytes in response to oxidative injury via reinforcing the endogenous antioxidant defense system. Therefore, it may be applied as an adjuvant therapy or in health foods to delay the skin aging process and the onset of skin diseases caused by oxidative stress.
Mast cells and basophils are key contributors to allergies and other inflammatory diseases since they are the most prominent source of histamine as well as numerous additional inflammatory mediators which drive inflammatory responses. However, a closer understanding of their precise roles in allergies and other pathological conditions has been marred by the considerable heterogeneity that these cells display, not only between mast cells and basophils themselves but also across different tissue locations and species. While both cell types share the ability to rapidly degranulate and release histamine following high-affinity IgE receptor cross-linking, they differ markedly in their ability to either react to other stimuli, generate inflammatory eicosanoids or release immunomodulating cytokines and chemokines. Furthermore, these cells display considerable pharmacological heterogeneity which has stifled attempts to develop more effective anti-allergic therapies. Mast cell- and basophil-specific transcriptional profiling, at rest and after activation by innate and adaptive stimuli, may help to unravel the degree to which these cells differ and facilitate a clearer understanding of their biological functions and how these could be targeted by new therapies.
Objective:
The roots of the herb Paeonia lactiflora ("White Peony") are used in association with other herbs in traditional clinical cosmetic practice in China as oral treatment for skin pigmentary disorders, such as brown or dark pigmentary spots. However, the skin depigmenting potential of Paeonia lactiflora root extract and its main ingredient paeoniflorin has been scarcely investigated by topical application. The purpose of this study was to evaluate the efficacy of Paeonia lactiflora root extract and paeoniflorin as skin whitening agent in cosmetic application.
Methods:
Paeonia lactiflora root extract (containing 53.25% of paeoniflorin) and paeoniflorin (97% purity) were applied topically on reconstructed pigmented human epidermis model, a three-dimensional (3D) human skin equivalent, showing morphological and functional characteristics similar to those of in vivo human skin. Two specific methods were used for quantifying melanin inside the reconstructed pigmented epidermis: image analysis of Fontana-Masson staining (2D quantification) and two-photon excited fluorescence images obtained with multiphoton microscopy (3D quantification).
Results:
Compared to vehicle (DMSO), a significant decrease of 2D and 3D melanin content was observed after topical application on reconstructed pigmented epidermis of Paeonia lactiflora extract at 300μg/mL (-28% and -27% respectively) and paeoniflorin at 120μg/mL/250μM (-30% and -23% respectively), which is in the same order of magnitude as the positive reference 4-n-butylresorcinol at 83μg/mL/500 μM (-26% and -40% respectively).
Conclusion:
These results demonstrate, for the first time, the depigmenting potential of paeoniflorin and thus the potential interest of using Paeonia lactiflora root extracts containing paeoniflorin in cosmetic or dermatological applications for reducing the severity of some hyper-pigmented skin disorders. This article is protected by copyright. All rights reserved.
This chapter discusses some of those aging related mechanisms and approaches that can be replicated and studied in vitro. The primary focus will be given to aging related mechanisms that have been shown in the literature to respond to compounds that could be used as ingredients in cosmetic or personal care products. In light of ever increasing scrutiny by both consumers and regulatory agencies, the testing of antiaging products is essential to ensure that the product will succeed in the marketplace by being safe, effective, and to substantiate advertising claims. While the methods discussed in the chapter are specifically used to screen compounds for antiaging effects and also provide some information on the mechanism of action of effective compounds, a review of scientific literature will reveal a variety of additional in vitro methods, which can detect aging related changes. These additional in vitro methods can be readily adapted to screen materials for antiaging effects and can also provide further insights into the mechanism behind a compound's antiaging properties. Once effective antiaging compounds have been identified and characterized through in vitro testing, they can proceed to the next phase of testing: in vivo testing. © 2009 William Andrew Inc. Published by Elsevier Inc. All rights reserved.
Background:
Anti-aging skin care is a growing popular topic in cosmetic and aesthetic fields, and skin care rather then makeup tips draw more attention nowadays. The phenomenon of skin aging includes thinning of skin losses of elasticity and moisture, pigmented spot formation, and wrinkle development. Along with growth in age, the decreased rates of epithelium renewal and cellular recovery as well as the reduced contents of elastin, collagen, and glycosaminoglycans all contribute to creases or folds of skin. Available strategies for wrinkle treatments include topical use of skin care products with anti-aging contents, dermabrasion, laser, Botox injection, fillers injection, and facelift. Though all of these above options can provide different degrees of improvement in facial wrinkles, the cost-effect, pain of intervention therapy, and necessity of repetitive treatment may impact on choices made. Topical use of anti-aging skin products is the most convenient and cheap way to achieve skin anti-aging effect. Lycogen(TM) is an antioxidant, which can prevent the downregulation of pro-collagen I, intracellular accumulation of malondialdehyde (MDA) and achieve the aim of skin rejuvenation.
Methods:
Twenty-six female patients were included in our study with ages between 30 and 45. They were randomly assigned to two groups: the vehicle control group and the experimental group. Patients in the control group applied a skin care product without Lycogen(TM)to the face via sonophoresis after facial cleanser use in the morning and at night. The experimental group applied a Lycogen(TM) -containing skin care product via sonophoresis in the same time schedule. We evaluated results, including pigmented spots, wrinkles, texture, pores, and red area by VISIA on weeks 0, 1, 2, 4, 6, 8, and 10 respectively.
Results:
In the aspect of pigmented spots, the experimental group showed significant difference in comparison with the vehicle control group on weeks 2, 6, 8, and 10. For wrinkles, the experimental group had better results on weeks 1, 2, 4, 8, and 10. Measured by texture, the experimental group had better results on weeks 1, 2, 4, 6, 8, and 10. Determined by pores, the experimental group had better results on weeks 2, 4, 6, 8, and 10. Concerning red areas, the experimental group had better results on weeks 6, 8, and 10. (p < 0.05).
Conclusion:
In our study, we applied a Lycogen(TM)- containing product by sonophoresis as the experimental group in comparison with a skin care product without LycogenTM. VISIA (Canfield Imaging Systems, Fairfield, NJ) was used to evaluate facial skin in aspects of pigmented spots, wrinkles, texture, pores, and red area. Overall, Lycogen(TM) had proven effectiveness on anti-oxidation as patients who used the Lycogen TM -containing product had better outcomes.
Background
Argireline is a synthetic peptide that is patterned from the N-terminal end of the protein SNAP-25 and has been shown to reduce the degree of facial wrinkles. It is reported to inhibit vesicle docking by preventing formation of the ternary SNARE complex and by interfering in catecholamine release. The anti-wrinkle efficacy of argireline has not been studied in Chinese subjects.
Objective
The objective of the study was to evaluate the safety and efficacy of argireline in the treatment of peri-orbital wrinkles in Chinese subjects.
Methods
A total of 60 subjects received a randomized treatment of argireline or placebo in a ratio of 3:1. Argireline or placebo was applied to their peri-orbital wrinkles twice daily for 4 weeks, and then evaluations were made for the improvements in wrinkles. In the subjective evaluation, Daniell’s classification and Seeman’s standard were applied to make a global assessment of changes in the appearance of peri-orbital lines. In the objective evaluation, silicone replicas of the skin at the application area were made before and after the treatment, which were analyzed by a wrinkle-analysis apparatus.
Results
In the subjective evaluation, the total anti-wrinkle efficacy in the argireline group was 48.9 %, compared with 0 % in the placebo group. In the objective evaluation, the parameters of roughness were all decreased in the argireline group (p < 0.01), while no decrease was obvious in the placebo group (p > 0.05).
Conclusions
This study showed that argireline had a significant anti-wrinkle effect in Chinese subjects.
A feature of the skin of many vertebrates is the presence of open grooves with characteristic intersecting geometric patterns. Here, we measure flows within the fine channels on the human skin surface and demonstrate that this network can act as a microfluidic device to allow the surface transport of liquids. Adapting a theory for fracture networks together with a treatment of capillary flow in a single V groove, we describe a model to account for the observed flows dependent on the groove shape, depth, and density of the grooves. This approach provides a simple framework for studying the regulation of fluid transport on the skin surface or on other similarly networked microchannels.
Rigorous research efforts have been undertaken worldwide to develop a needle-free insulin delivery for many decades with limited success. This translational study aims to deliver insulin through skin with painless electroporation.
A recently designed microelectrode array was used to deliver insulin in mice with diabetes under electroporation conditions that are painless and harmless on human skin.
Under such condition, a therapeutic amount of insulin was delivered successfully through mouse skin. Electroporation alone increased insulin transport around 100-fold compared with passive diffusion. Increased skin temperature to 40°C for 20 min augmented insulin transport to 237-fold more than the control value. Repeated electroporation showed no harm on human skin.
The results indicate the potential of painless delivery of insulin through human skin in future clinical practice.
For the evaluation and quantification of follicular penetration processes, the knowledge of variations of hair follicle parameters in different body sites is basic. Characteristics of follicle sizes and potential follicular reservoir were determined in cyanoacrylate skin surface biopsies, taken from seven different skin areas (lateral forehead, back, thorax, upper arm, forearm, thigh, and calf region). The highest hair follicle density and percentage of follicular orifices on the skin surface and infundibular surface were found on the forehead, whereas the highest average size of the follicular orifices was measured in the calf region. The highest infundibular volume and therefore a potential follicular reservoir was calculated for the forehead and for the calf region, although the calf region showed the lowest hair follicle density. The calculated follicular volume of these two skin areas was as high as the estimated reservoir of the stratum corneum. The lowest values for every other parameter were found on the forearm. The present investigation clearly contradicts former hypothesis that the amount of appendages of the total skin surface represents not more than 0.1%. Every body region disposes its own hair follicle characteristics, which, in the future, should lead us to a differential evaluation of skin penetration processes and a completely different understanding of penetration of topically applied drugs and cosmetics.