ArticleLiterature Review

Morita ATobacco smoke causes premature skin aging. J Dermatol Sci 48:169-175

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Abstract

Smoking tobacco is the most preventable cause of morbidity and is responsible for more than three million deaths a year worldwide. In addition to a strong association with a number of systemic diseases, smoking is also associated with many dermatological conditions, including poor wound healing, premature skin aging, squamous cell carcinoma, melanoma, oral cancer, acne, psoriasis, and hair loss. This review focuses on the effects of smoking on premature skin aging. It has been long established that smoking has deleterious effects on skin. Epidemiological studies indicate that smoking is an important environmental factor in premature skin aging. In vitro studies indicate that tobacco smoke extract impairs the production of collagen and increases the production of tropoelastin and matrix metalloproteinases (MMP), which degrade matrix proteins, and also causes an abnormal production of elastosis material. Smoking increases MMP levels, which leads to the degradation of collagen, elastic fibers, and proteoglycans, suggesting an imbalance between biosynthesis and degradation in dermal connective tissue metabolism. Reactive oxygen species are also involved in tobacco smoke-induced premature skin aging. Scavengers of reactive oxygen species ameliorate the induction of MMP. Tobacco smoke extract also impacts dermal connective tissue in nude mice. Thus, in vitro and in vivo evidence indicates that smoking tobacco leads to accelerated aging of the skin. These findings might be useful to motivate those patients who are more concerned about their appearance than the potential internal damage associated with smoking to stop smoking.

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A detailed appreciation of the development, structure and function of human skin is fundamental to understanding diseases that originate in or target the skin. Recent advances in molecular science have provided fascinating new insights into stem cell biology and skin homeostasis as well as disease processes such as inflammation, wound healing, ageing and neoplasia, providing novel opportunities to improve the diagnosis and therapy of skin diseases.
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Background 7,3′,4′-Trihydroxyisoflavone (734THI), a secondary metabolite derived from daidzein in soybean, possesses several biological activities, including antioxidant, skin whitening and anti-atopic dermatitis properties, but the poor aqueous solubility of 734THI has limited its application in medicine and cosmetic industry. Methods The aim of the present study was to improve the physicochemical properties of 734THI using planetary ball mill preparation under a solvent-free process to improve its solubility and anti-pollutant activity. Results 734THI nanoparticle powder (734THIN) was successfully prepared by the planetary ball mill technique using polyvinylpyrrolidone K30 as the excipient. 734THIN effectively increased the aqueous solubility and cellular uptake of 734THI by improving its physicochemical properties, including particle size reduction, crystalline–amorphous transformation and intermolecular hydrogen bonding with polyvinylpyrrolidone K30. In addition, 734THIN inhibited the overexpression of COX-2 and MMP-9 by downregulating MAPK pathway signaling in particulate matter-exposed HaCaT keratinocytes, while raw 734THI in PBS with low aqueous solubility did not show any anti-inflammatory or antiaging activity. Conclusion 734THIN may be used as an additive in anti-pollutant skin care products for preventing particulate matter-induced inflammation and aging in skin.
Article
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Article
Aims and background There are several barriers to smoking cessation that are unique to women. Compared to men, women report lower levels of motivation to quit and greater perceived difficulty with cessation. However, recent studies might favor commitment by women to quit through higher risk perception related e.g. to the development of premature facial wrinkling or the decrease in mammographic density due to cigarette smoking. Methods A pilot study to evaluate the perception of breast change after cessation and its possible motivational effect on maintenance was carried out. We interviewed 25 premenopausal women who had quit ≥1 year before. We obtained information from the women and discussed changes in breast size and fullness. The two groups of women with and without breast change were statistically compared using the non-parametric Mann-Whitney test (continuous variables) and the Fisher test (categorical variables). Results Median age was 41 years (range, 30–49 years). Median carbon monoxide (CO) before quitting was 18 ppm and median pack years (PY) was 22.5; both parameters characterize a category of mild smokers. Sixteen women (64%) reported breast changes 6 months after quitting smoking. This outcome was paralleled by only moderate effects on weight or body mass index (BMI) increase after quitting. Notably, of the 16 women with breast change, only 3 (19%) with a normal baseline BMI showed a BMI increase to >25. Conclusions Within the limitations of the small size of a pilot study, these results indicate that premenopausal women experience subjective perception of change in breast size after smoking cessation, which may not be totally explained by weight gain. Further studies are needed to understand the effect, if any, of such perception on the motivation to quit smoking.
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It remains important to investigate skin ageing signs across different skin types for targeted solutions. Limited data is available on Indian skin changes throughout ageing, hence three fields were investigated: skin features during the ageing process, their relationship with perceived age and self-declared skin ageing concerns. Photographs, skin topography, colour and biophysical measurements of 202 Indian female volunteers, 30-65 years old, were collected. Another panel of 693 naïve graders, 20-65 years old, estimated the age of photographs previously collected. Associations between 28 skin features and real/perceived age were assessed using linear correlation coefficients. Skin feature scores of an older perceived group were compared versus the scores of a younger perceived group, to establish skin features that lead to an older appearance. Additionally, the naïve graders were asked to rank 12 skin ageing concerns by importance. Twenty-four features correlated with real and perceived age. The ages of the volunteers were overestimated, especially those in their 30s. Skin features related to skin brightness suggested an older look for volunteers in their 30s. From the 40s onwards, wrinkles around the eye area, glabellar and corner of the mouth were also drivers for looking older. In the 50s, features such as upper lip wrinkles, hydration and roughness on the crow's feet were worse in the older perceived group, while nasolabial folds suggested an older appearance in the 60s. By having identified skin features that worsen with age and contribute to an older perceived face, this research will facilitate the creation of tailored products and communication for Indian women to look after their skin concerns throughout the ageing process.
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The skin, the largest organ in humans, is exposed to major sources of outdoor air pollution, such as fine particulate matter with a diameter ≤ 2.5 µm (PM2.5). Diphlorethohydroxycarmalol (DPHC), a marine-based compound, possesses multiple activities including antioxidant effects. In the present study, we evaluated the protective effect of DPHC on PM2.5-induced skin cell damage and elucidated the underlying mechanisms in vitro and in vivo. The results showed that DPHC blocked PM2.5-induced reactive oxygen species generation in human keratinocytes. In addition, DPHC protected cells against PM2.5-induced DNA damage, endoplasmic reticulum stress, and autophagy. HR-1 hairless mice exposed to PM2.5 showed lipid peroxidation, protein carbonylation, and increased epidermal height, which were inhibited by DPHC. Moreover, PM2.5 induced apoptosis and mitogen-activated protein kinase (MAPK) protein expression; however, these changes were attenuated by DPHC 5. MAPK inhibitors were used to elucidate the molecular mechanisms underlying these actions, and the results demonstrated that MAPK signaling pathway may play a key role in PM2.5-induced skin damage.
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Background: Skin acts as a mirror to the internal state of the body. Hypothesis: We tried to find the relation between skin aging parameters and the incidence of degenerative AV block. Methods: This study included 97 patients divided into 2 groups; group D comprised 49 patients with advanced-degree AV block, and group C comprised the 48 matched control group. All were subjected to full history taking, thorough clinical examination, calculation of intrinsic skin aging score, and resting 12-lead surface electrocardiography (ECG). ECG for all patients assessed left ventricular end-systolic diameter, left ventricular end-diastolic diameter, ejection fraction, left atrium (LA) diameter, aortic root diameter, mitral annular calcification, aortic sclerosis. Coronary angiography was also performed when indicated for patients in group D. Results: Patients in group D had a higher percentages of uneven pigmentation, fine skin wrinkles, lax appearance, seborrheic keratosis, total score > 7 (38 [77.55%] vs 10 [20.83%]), mitral annular calcification score of 33 (67.34%) vs 5 (10.41%), aortic sclerosis score of 21 (42.85%) vs 4 (8.33%), and mean LA diameter of 39.98 ± 5.52 vs 36.21 ± 3 mm (P < 0.001). Total score > 6 is the best cutoff value to predict advanced-degree heart block with 89.79% sensitivity and 64.58% specificity. Seborrheic keratosis was the strongest independent predictor. Conclusions: Any population with a total intrinsic skin aging score of >6 is at high risk for developing advanced-degree AV block and should undergo periodic ECG follow-up for early detection of any conduction disturbance in the early asymptomatic stages to minimize sudden cardiac death.
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Corneal crosslinking (CXL) is performed in an outpatient setting. Thirty minutes in advance, a systemic analgosedation can be administered. Some surgeons use Pilocarpin 2% eye drops in order to reduce potential thermal and photochemical effects of UVA-radiation on the retina and the lens.
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Objectives: The skin is a dynamic, visible organ, showing the most obvious signs of aging. The mechanisms of extrinsic aging, most of them presented in this paper, are currently well known and also the only ones that can be counteracted. Therefore, the transition of this knowledge in the general population is of the most importance, in order to introduce healthy aging strategies, to prevent the development of chronic or malignant diseases and psychological burden related to old age. Materials and methods: A thorough review of the literature has been performed in order to identify the main factors involved in skin health and aging. Outcomes: This concept article represents a compilation of seven anti-ageing directions regarding major factors involved in health, aging and beauty, respectively sun, sugar, smoking, skin care, stress, sleep and second (the passage of time), easy to comprehend by the general public but sustained by a strong scientific documentation. Conclusions: Despite its final destination, every quality concept has to pass through academic purgatory as, once accepted, it comes to respond to ever more educated society’s demands in terms of anti-ageing.
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Introduction: The skin acts as a barrier and prevents transcutaneous delivery of therapeutic agents. Transfersomes are novel vesicular systems that are several times more elastic than other vesicular systems. These are composed of edge activator, phospholipids, ethanol, and sodium cholate and are applied in a non-occlusive manner. Areas covered: This article covers information such as merits/demerits of transfersomes, regulatory aspects of materials used in preparation, different methods of preparation, mechanism of action, review of clinical investigations performed, marketed preparations available, research reports, and patent reports related to transfersomes. Expert opinion: Research over the past few years has provided a better understanding of transfersomal permeation of therapeutic agents across stratum corneum barrier. Transfersomes provides an essential feature of their application to variety of compositions in order to optimize the permeability of a range of therapeutic molecules. This is evidenced by the fact that there are several Transfersome products being processed in advanced clinical trials. It is noteworthy that a number of Transfersome products for dermal and transdermal delivery will gain a global market success in near future.
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A recent study has revealed that 30% of women believe stress and anxiety has caused them to age the most since turning 30. This is despite lifestyle choices, such as sun exposure and smoking, being regularly cited as causes of ageing. Rekha Tailor discusses the importance of educating patients on both the contributing factors of skin ageing and how they can make changes which will benefit their skin
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Skin aging is a complex process that is categorized into either intrinsic or extrinsic actinic aging. Extrinsic actinic aging results from environmental factors, namely ultraviolet (UV) radiation, which is commonly referred to as photoaging, and is characterized by wrinkles and dryness. In contrast to extrinsic aging, intrinsic aging is gene dependent and occurs over time due to variety of physiological factors (ex/ hormonal changes). Numerous studies have been performed in an attempt to understand how the architecture of the skin changes with age and to uncover the mechanism by which this occurs [1]. There is also a large body of studies focused on determining how to prevent and reverse the effects of photoaging. As such, providing an in-depth review of the literature would not be possible in a single chapter. Therefore, the aim of this chapter is to lay a general framework of the various studies that have been performed in animal models regarding skin aging and to highlight what conclusions can be drawn from them and what has yet to be uncovered.
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Cellulite, also known as gynoid lipodystrophy, is a multifactor disorder of the dermis, epidermis, and subcutaneous cellular tissue (Goldman et al. Pathophysiology of cellulite. New York: Taylor & Francis; 2006). In most cases, this alteration occurs in postpubertal women with a prevalence of 80–90 % (Goldman and Hexsel. Cellulite: pathophysiology and treatment. 2nd ed. Florida: Editorial Informa, Healthcare; 2010; Emanuele. Clin Dermatol 31(6):725–30, 2013). Clinically, cellulite presents irregularity of the skin surface with depressions, lumps, and nodules associated with laxity. Usually, cellulite is located in the abdomen, buttocks, and lower limbs, but it can also occur on the arms and the back. Histologically, cellulite is caused by subcutaneous herniated fat within the fibrous connective tissue (Rossi and Vergnanini. JEADV 14: 251–62, 2000; Khan et al. J Am Acad Dermatol. 62(3):361–70, 2010; De Peña and Hernández-Pérez. Rev Cent Dermatol Pascua 3:132–5, 2005). An increase in the thickness of the subcutaneous cellular tissue is also observed. Although cellulite is still considered as an unclear etiological condition, there are many hypotheses trying to explain this disorder. Treatments can be invasive and noninvasive. Invasive methods include subcision and mesotherapy, as well as liposuction when patients also want to remove excessive localized fat. Noninvasive treatments include topical treatments, controlled diets, cryolipolysis, focused ultrasound, endermology, laser, and non-ablative radiofrequency. In this chapter we are going to discuss the treatment with non-ablative radiofrequency. Radiofrequency (RF) contracts collagen and stimulates neocollagenesis by thermal heat, promoting thickening of the dermis, avoiding fat herniation. It can also promote improvement in local circulation due to the vasodilatation and lymphatic drainage. Clinically it improves the laxity and the irregularity of the skin surface (Coringrato et al. Radiofrecuencia ablativa en dermatología quirúrgica: Una revisión, Rev. dermatología argentina, vol. XIV, Julio–Septiembre 2008, Número 3; Brightman et al. Lasers Surg Med 41:791–8, 2009).
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For its critical location, the skin represents the major interface between the body and the environment, therefore is one of the major biological barriers against the outdoor environmental stressors. Among the several oxidative environmental stressors, cigarette smoke (CS) has been associated with the development and worsening of many skin pathologies such as acne, dermatitis, delayed wound healing, aging and skin cancer. In our previous work we have demonstrated that CS is able to affect genes involved in skin cholesterol trafficking, among which SRB1, a receptor involved in the uptake of cholesterol from HDL, seems to be very susceptible to the oxidative stress induced by CS.
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This chapter discusses in detail all the various factors that affect the process of skin aging. Skin aging depends upon a combination of intrinsic and extrinsic factors. Intrinsic factors include gender, ethnicity, and anatomical variations, which are genetically determined. Extrinsic factors such as lifestyle, nutrition, smoking, and sun exposure can also accelerate skin aging. Most intrinsic factors cannot be avoided, but extrinsic factors, such as sun exposure and smoking, can be reduced or eliminated, with substantial impact on the visible appearance of the skin. Lifestyle factors such as smoking or nutritional choices can modulate the effects of both genetic and environmental aging. Exposure to solar ultraviolet light initiates a flurry of molecular and cellular responses that promote rapid and dynamic changes in the skin. Greater understanding of the molecular processes which contribute to skin aging, as well as how lifestyle choices accelerate or impede those changes, may help improve both physical and psychological health for the increasing percentage of the population in the latter years of their lives.
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Self-efficacy regarding the ability to stop smoking is considered a key factor for successful smoking cessation. However, research has found a weak link between self-efficacy and the intention to stop smoking. The present study aimed to gain a clearer understanding of this weak link, hypothesizing opposing effects of self-efficacy regarding the intention to quit. A representative sample of daily smokers in Switzerland (N = 362) completed a questionnaire. As expected, two opposing effects of self-efficacy were found: Self-efficacy was directly associated with the intention to quit, but self-efficacy was negatively linked to risk perception, resulting in a weakened intention to quit. This model explains the overall weak effect of self-efficacy on intention to quit. However, contrary to the hypotheses, dependence was not found to moderate the relationship between self-efficacy and intention to quit. Implications for interventions and future research are discussed. © 2019, © 2019 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.
Article
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Although lactic acid bacteria (LAB) were shown to be effective for preventing photoaging, the underlying molecular mechanisms have not been fully elucidated. Accordingly, we examined the anti-photoaging potential of 206 LAB isolates and discovered 32 strains with protective activities against UV-induced injury. All of these 32 LABs exhibited high levels of 2,2-diphenyl-picrylhydrazyl, as well as hydroxyl free radical scavenging ability (46.89–85.13% and 44.29–95.97%, respectively). Genome mining and metabonomic verification of the most effective strain, Limosilactobacillus fermentum XJC60, revealed that the anti-photoaging metabolite of LAB was nicotinamide (NAM; 18.50 mg/L in the cell-free serum of XJC60). Further analysis revealed that LAB-derived NAM could reduce reactive oxygen species levels by 70%, stabilize the mitochondrial membrane potential, and increase the NAD+/NADH ratio in UV-injured skin cells. Furthermore, LAB-derived NAM downregulated the transcript levels of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-1β, IL-6, and IL-8 in skin cells. In vivo, XJC60 relieved imflammation and protected skin collagen fiber integrity in UV-injured Guinea pigs. Overall, our findings elucidate that LAB-derived NAM might protect skin from photoaging by stabilizing mitochondrial function, establishing a therotical foundation for the use of probiotics in the maintenance of skin health.
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Smoking has a negative influence on human beings. Carcinogens detected in smoke can increase the risk of developing chronic disorders, cancer and premature death. Nicotine can also affect dermatological diseases such as psoriasis, hidradenitis suppurativa, chronic dermatoses, alopecia, lupus erythematosus, polymorphous light eruption, skin cancer and tobacco-associated oral lesions. Advanced education at a doctor's surgery in various medical occupations can change the bad habits and protect people from the consequences.
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Cigarette smoke (CS) alters cutaneous biological processes such as redox homeostasis and inflammation response that might be involved in promoting skin inflammatory conditions. Exposure to CS has also been linked to a destabilization of the NLRP3 inflammasome in pollution target tissues such as the lung epithelium, resulting in a more vulnerable immunological response to several exogenous and endogenous stimuli related to oxidative stress. Thus, CS has an adverse effect on host defense, increasing the susceptibility to develop lung infections and pathologies. In the skin, another direct target of pollution, inflammasome disorders have been linked to an increasing number of diseases such as melanoma, psoriasis, vitiligo, atopic dermatitis, and acne, all conditions that have been connected directly or indirectly to pollution exposure. The inflammasome machinery is an important innate immune sensor in human keratinocytes. However, the role of CS in the NLRP1 and NLRP3 inflammasome in the cutaneous barrier has still not been investigated. In the present study, we were able to determine in keratinocytes exposed to CS an increased oxidative damage evaluated by 4-HNE protein adduct and carbonyl formation. Of note is that, while CS inhibited NLRP3 activation, it was able to activate NLRP1, leading to an increased secretion of the proinflammatory cytokines IL-1β and IL-18. This study highlights the importance of the inflammasome machinery in CS that more in general, in pollution, affects cutaneous tissues and the important cross-talk between different members of the NLRP inflammasome family.
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The exposome has an impact on skin from life-long exposure. Acute short-term exposure to exposome stressors can also alter skin functions such as skin physical barrier and immune defenses, leading to skin dryness, sensitivity, flares of inflammatory skin conditions, or viral reactivations. Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. An extract produced by lysing Vitreoscilla filiformis (VfeV) cultured in Vichy volcanic mineralizing water (VVMW) has properties of probiotic fractions. In this review, we present in vivo and ex vivo studies with a dermocosmetic formulation containing 80% VVMW, 5% VfeV, 4% niacinamide (vitamin B3), 0.4% hyaluronic acid, and 0.2% vitamin E (M89PF) to evaluate the clinical efficacy in preventing and repairing stressed skin. Skin barrier benefits of M89PF were shown in studies after the skin was exposed to sudden thermal changes, after skin irritation by tape stripping, and in sleep-deprived women. M89PF significantly accelerated skin renewal compared to untreated skin. Skin antioxidant defense activity of M89PF was shown after exposure to stress from UVA plus cigarette smoke aggression. Skin microbiome recovery after acute stress from a harsh cleanser was significantly better in M89PF-treated skin compared to bare skin. Clinical benefits of M89PF on correcting clinical signs of stressed skin were shown in both Caucasian and Asian women exposed to a stressful lifestyle and various external (pollution, tobacco smoking, solar radiation) and internal (poor sleep, stressful work, unbalanced diet, and alcohol consumption) exposome factors. M89PF also showed depigmenting properties on dark spots in Asian women. Further clinical studies are now warranted to evaluate the efficacy of M89PF as adjuvant care to prevent and repair skin barrier disruption and reinforce skin defenses in skin exposed to acute stresses.
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The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.
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Background: Exposure to solar radiation has been documented as a direct cause of skin changes associated with aging, and its effects have been categorized as photoaging. Objective: To explore the clinical characteristics of photoaging and its relationship with external predisposing factors in a Colombian urban and rural population. Methods: We included 350 patients on outpatient consultation at Clínica Chía in Zipaquirá (rural) and Hospital Universitario Barrios Unidos in Bogotá (urban) in an observational, cross-sectional study with an analytical component included, between 2018 and 2019. A survey was conducted and photographs were taken. A group of experts determined the degree of photoaging. Results: The majority of respondents worked in closed environments (n = 222). The main sociodemographic variable associated was age (p = 0.000). Factors such as smoking, alcohol consumption, use of sunscreen, exercising, and sun exposure were also associated with scale progression (p < 0.05). Exercising (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.3-0.9) and being from Bogotá (OR 0.6, 95% CI 0.2-0.9) appeared as protective factors. Smoking (OR 1.6, 95% CI 1.0-2.6) was defined as a risk factor. Conclusions: Changes related to photoaging and photocarcinogenesis are associated with sun exposure. However, there are environmental factors, such as smoking, alcohol consumption, sedentary lifestyle, woman's age at first delivery, and number of children, among others, that affect the degree of photoaging. It is necessary to explore these relationships in higher evidence level studies to define their causality.
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Skin aging is the most visible element of the aging process, giving rise to a major concern for many people. Plants from the Ericaceae family generally have antioxidant and anti-inflammatory properties, making them potential anti-aging active ingredients. This study aimed to evaluate the safety and anti-aging efficacy of a Kalmia angustifolia extract using reconstructed skin substitutes. The safety evaluation was performed using a 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, while the efficacy was determined by assessing antioxidant and anti-inflammatory activity and analyzing skin substitutes reconstructed according to the self-assembly method by histology and immunofluorescence staining (elastin, collagen-1, collagen-3, aquaporin-3). The cell viability assay established the safety of the extract at a concentration up to 200 μg/mL. The Oxygen Radical Absorbance Capacity (ORAC) assay and a cell-based assay using 2’,7’-dichlorofluorescein-diacetate (DCFH-DA) revealed a strong antioxidant activity with an ORAC value of 16 µmol Trolox Equivalent/mg and a half-maximal inhibitory concentration (IC50) of 0.37 ± 0.02 μg/mL, while an interesting anti-inflammatory activity was found in the inhibition of NO production, with an inhibition percentage of NO production of 49 ± 2% at 80 µg/mL. The isolation and characterization of the extract allowed the identification of compounds that could be responsible for these biological activities, with two of them being identified for the first time in K. angustifolia: avicularin and epicatechin-(2β-O-7, 4β-6)-ent-epicatechin. Histological analyses of skin substitutes treated with the extract showed an increase in dermal thickness compared with the controls. K. angustifolia extract enhanced the expression of elastin and collagen-1, which are usually decreased with skin aging. These results suggest that K. angustifolia has promising antioxidant efficacy and anti-aging potential.
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BACKGROUND: Skin aging can be a contributing factor in the prediction, follow-up, and early diagnosis of some disorders related to the aging process, including degenerative cardiovascular diseases. OBJECTIVE: We sought to explore the association between a clinical skin aging score and risk of degenerative heart diseases. METHODS: This study included two groups; a case group consisting of 44 patients older than 30 years who were admitted to the cardiology department with degenerative heart disease and 44 age- and sex-matched healthy individuals to act as a control group. The skin aging score was calculated for all subjects. RESULTS: Regarding intrinsic skin aging parameters, there were highly significant differences between the two groups in uneven pigmentation, reduced fat tissue, benign skin tumors, fine wrinkles, and lax skin appearance. Concerning extrinsic skin aging parameters, there were significant differences between the two groups regarding pigment changes, changes in skin phenotype, yellowness, pseudoscars, cutis rhomboidalis nuchae, telangectasia, coarse wrinkles, and dryness. CONCLUSION: Our study suggests that any individual with intrinsic skin aging score greater than eight points or total score of more than 15 points is at high risk for degenerative cardiovascular disease and should undergo periodic follow-up.
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Background Visual and molecular changes occurring upon aging are rather well characterized. Still, aging signs show great significant inter-individual variations, and little is known concerning the link between perceived age and cutaneous microcirculation. Materials and Methods To investigate this point, we recruited Caucasian women in their mid-50's to mid-70's and subsampled women looking older or younger than their age. We studied their facial skin color, as well as their microvascular reactivity to local heating assessed in the forearm skin. We also used skin biopsies from some of these women for gene expression or immunohistochemical analysis. Results Clinical and instrumental analysis of skin color revealed that subjects who look 5 years younger differ only by a higher glowing complexion. Our most striking result is that subjects looking 5 years younger than their age present a higher microcirculation reactivity in forearm skin. Transcriptome comparison of skin samples from women looking older or younger than their age revealed 123 annotated transcripts differentially expressed, among which MYL9 relates to microcirculation. MYL9 is downregulated in the group of women looking younger than their real age. Microscopy shows that the labeling of MYL9 and CD31 are altered and heterogeneous with age, as is the morphology of microvessels. Conclusion Therefore, assessing generalized vascular reactivity in non-photo-exposed skin to focus on the intrinsic aging allows subtle discrimination of perceived age within elderly healthy subjects.
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Formation of oxidative stress in dermal fibroblasts plays crucial roles in aging processes of skin. The use of phytochemicals that can promote capacity of fibroblasts to combat oxidative stress is an attractive strategy to prevent skin aging and promote skin beauty. Centella asiatica has been used to treat multitude of diseases for centuries. Previous investigations demonstrated that extracts from C. asiatica have a broad range of beneficial activities through their antioxidant activity. Hence, the extract from this medicinal plant could be a great candidate for anti-skin-aging agent. Callus culture offers a powerful platform for sustainable, rapid and large-scale production of phytochemicals to serve extensive demands of pharmaceutical and cosmeceutical industries. Here, we demonstrated the application of callus culture of Centella asiatica to produce bioactive metabolites. The 50% ethanolic extract of callus culture has distinctive features of chemical compositions and biological profiles. Information from HPTLC-DPPH and HPLC analysis suggested that the callus extract comprises distinctive antioxidant compounds, compared with those isolated from authentic plant. Moreover, results from cell culture experiment demonstrated that callus extract possesses promising antioxidant and anti-skin-aging activities. Pre-treatment with callus extract attenuated H 2 O 2 -induced-cytotoxicity on human dermal fibroblasts. The results from RT-qPCR clearly suggested that the upregulation of cellular antioxidant enzymes appeared to be major contributor for the protective effects of callus extract against oxidative stress. Moreover, supplementation with callus extract inhibited induction of matrix metalloprotease-9 following H 2 O 2 exposure, suggesting its potential anti-skin-aging activity. Our results demonstrate the potential utility of C. asiatica callus extract as anti-skin-aging agent in cosmeceutical preparations.
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Automatic facial wrinkles detection and inpainting algorithms have gained attention of researchers in cosmetics, forensics and computer vision. The majority of current inpainting algorithms was implemented on the whole face, despite the fact that only imperfections need inpainting. In general, the definition of an imperfection is sign of ageing, spot, scar and freckles. This paper focuses on wrinkles as it is an obvious sign of ageing. We survey the computer vision techniques in facial wrinkles localisation from detection to inpainting. We present a comprehensive literature review on benchmark datasets, automated wrinkles detection algorithms and facial inpainting algorithms. Due to limited study on wrinkle inpainting, we inpaint the wrinkle regions using three state-of-the-art inpainting algorithms, namely flood-fill, Coherence Sensitivity Hashing and exemplar-based method. To assess the realism of inpainting results, we present the original and inpainted images to 40 participants, where they provide rating on the realism scale and age group of each image. The result shows that flood-fill method preserved the realism but there was no significant difference in age prediction. Finally, we conclude the paper by proposing some future directions to advance this field.
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Background The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin‐microbiome interactions are still insufficiently characterized. This contrasts to the broader knowledge about the factors influencing the gut microbiota. Objectives We aimed to investigate major patterns of associations of host traits, lifestyle, and environmental factors with skin bacteria in two German populations. Methods This is a cross‐sectional study with 647 participants from two population‐based German cohorts, PopGen (n=294) and KORA FF4 (n=353), totaling 1794 skin samples. The V1‐V2 regions of the 16S rRNA gene were sequenced. Associations were tested with two bacterial levels, community (beta‐diversity) and 16S rRNA gene amplicon sequence variants (ASVs). Results We validated known associations of the skin microbiota with skin microenvironment, age, body mass index (BMI) and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education, and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium, and Staphylococcus. Discussion We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with the skin bacteria. Finally, we hypothesize that the skin microenvironment and the host physiology would shape the skin bacterial community at greater extent in comparison to a single skin physiological feature, lifestyle and environmental exposition.
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Bei legalen Drogen handelt es sich um Substanzen, die einfach und rechtmäßig erhältlich sind. Der Konsum und Besitz von diesen Substanzen und der Handel mit ihnen sind straffrei und sie können im Supermarkt, am Kiosk oder in der Tankstelle um die Ecke erworben werden. Doch Vorsicht: Legal bedeutet auf keinen Fall, dass diese Substanzen harmlos sind, denn den Körper interessiert das kleine Wörtchen „legal“ kein bisschen, und nur weil diese Suchtmittel ohne strafrechtliche Folgen zu erwerben sind, rechtfertigt dies die negativen Folgen für Gesundheit und Lebensqualität nicht.
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Introduction: The goal of our prospective study was to assess the efficacy of the topical Platelet-rich plasma on reducing superficial perioral wrinkles and restoring the dermal matrix. Materials and methods: 50 women with moderate to severe perioral wrinkles were treated on the perioral area by a single session of fractional CO2 laser skin resurfacing plus intradermal injection of prp. 25 patients (group 1) applied topically prp twice a day for 12 weeks as post laser treatment. 25 (group 2) applied gentamicin and betamethasone twice a day for the first 7 days and then hyaluronic acid gel for the following 12 weeks. Results: In group 1, moisture (p < 0.001), amount of collagen fiber (p < 0.001) skin elasticity (p < 0.001), PSAl (p < 0.001) and SSAl (p < 0.001) improved significantly. In group 2 all the parameters investigated improved but did not reach significant difference. Discussion: Our medical device with a plasma-like formulation is able to maintain prp active for a period of 7 days so patients are able to apply topically growth factors at home. Conclusions: Our prospective study proves that the use of topical prp reduces superficial perioral wrinkles and restore dermal matrix when used at home for 12 weeks.
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Background A new topical formulation (TF) based on 3 main lifting components has been developed to reduce superficial facial wrinkles. Objectives Determine the effectiveness of this new TF in reducing superficial face wrinkles and restructuring the dermal matrix. Methods Women, aged 30‐65 y.o. with moderate to severe crow's feet wrinkles were included. Exclusion criteria: men; younger than 30 or older than 65 years old; smokers. Patients received 15 IU of botulinum toxin on crow's feet and 2 creams. Fifty patients (Group 1) applied the TP (Product A) and 50 (Group 2) a placebo (Product B). Assessments were made by digital macro‐photography's, Antera 3D, and a patient satisfaction questionnaire. Results From April to June 2019, 100 women were enrolled in the study and were divided into two homogeneous groups. No major or minor side effects were reported. In group 1, wrinkles, texture, static and dynamic crow's feet wrinkles improved significantly at 3 and 6 months. Patients were very satisfied at 3 months and satisfied at 6 months. In group 2, wrinkles and texture improved significantly at 3 months but did not improve at 6 months. Static and dynamic crow's feet wrinkles improved significantly at 1 and 3 months but did not improve significantly at 6 months. Conclusions Our prospective and randomized study has shown that the new TF is safe and effective in reducing superficial face wrinkles and producing dermal regeneration. It, therefore, prolongs the duration of the botulinum toxin. Further controlled study would be necessary to compare the new TF to neurotoxin treatment, or its action alone.
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Pollution is being shown increasingly to play an role in some of our most common diseases and skin is no exception. It is important to consider pollution as a risk factor for causation of a variety of skin disorders and to include management strategies in patient discussions. To those practioners in high pollution areas, a generational approach of prevention is recommended. Introduce anti-pollution dietary and skin care routines at an early age to promote the healthiest, cleanest skin possible and to mitigate evolving pollution related skin disorders. (Roberts, 2013)
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The periorbital region is a difficult area to treat because of its delicate nature, thinnest part in the body and important function. Careful treatment of the anatomic eyelid structure is crucial in order to avoid any complications. Proper patient selection and assessment of aging severity is important in order to determine the best therapeutic option. With advances in cosmetic medicine, minimally invasive techniques in aesthetic rejuvenation have become increasingly popular. Topical therapy, chemical peels, laser resurfacing, plasma resurfacing, radiofrequency and surgery, along with neuromodulators and fillers, can be used to enhance the appearance of the periorbital region. The objective of this chapter is to review common applications of lasers and energy-based devices for the treatment of periorbital concerns.
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Electronic cigarette (e-cig) usage has risen dramatically worldwide over the past decade. While they are touted as a safe alternative to cigarettes, recent studies indicate that high levels of nicotine and flavoring chemicals present in e-cigs may still cause adverse health effects. We hypothesized that an e-liquid containing a mixture of tobacco, coconut, vanilla, and cookie flavors would induce senescence and disrupt wound healing processes in pulmonary fibroblasts. To test this hypothesis, we exposed pulmonary fibroblasts (HFL-1) to e-liquid at varying doses and assessed cytotoxicity, inflammation, senescence, and myofibroblast differentiation. We found that e-liquid exposure caused cytotoxicity, which was accompanied by an increase in IL-8 release in the conditioned media. E-liquid exposure resulted in elevated senescence-associated beta-galactosidase (SA-β-gal) activity. Transforming growth factor-β1 (TGF-β1) induced myofibroblast differentiation was inhibited by e-liquid exposure, resulting in decreased α-smooth muscle actin and fibronectin protein levels. Together, our data suggest that an e-liquid containing a mixture of flavors induces inflammation, senescence and dysregulated wound healing responses.
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Background: Lung aging is characterized by a number of structural alterations including fibrosis, chronic inflammation and the alteration of inflammatory cell composition. Chronic exposure to cigarette smoke (CS) is known to induce similar alterations and may contribute to premature lung aging. Additionally, aging and CS exposure are associated with transcriptional alterations in the lung. The current work aims to explore the interaction between age- and CS- associated transcriptomic perturbations and develop a transcriptomic clock able to predict the biological age and the impact of external factors on lung aging. Results: Our investigations revealed a substantial overlap between transcriptomic response to CS exposure and age-related transcriptomic alterations in the murine lung. Of particular interest is the strong upregulation of immunoglobulin genes with increased age and in response to CS exposure, indicating an important implication of B-cells in lung inflammation associated with aging and smoking. Furthermore, we used a machine learning approach based on Lasso regression to build a transcriptomic age model that can accurately predict chronological age in untreated mice and the deviations associated with certain exposures. Interestingly, CS-exposed-mice were predicted to be prematurely aged in contrast to mice exposed to fresh air or to heated tobacco products (HTPs). The accelerated aging rate associated with CS was reversed upon smoking cessation or switching to HTPs. Additionally, our model was able to predict premature aging associated with thoracic irradiation from an independent public dataset. Conclusions: Aging and CS exposure share common transcriptional alteration patterns in the murine lung. The massive upregulation of B-cell restricted genes during these processes shed light on the contribution of cell composition and particularly immune cells to the measured transcriptomic signal. Through machine learning approach, we show that gene expression changes can be used to accurately monitor the biological age and the modulations associated with certain exposures. Our findings also suggest that the premature lung aging is reversible upon the reduction of harmful exposures.
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Introduction: People whose faces look untrustworthy tend to receive harsher social evaluations, including more severe criminal sentences. Yet little is known about how much facial trustworthiness reflects individuals' behavioral histories. We examined whether adolescent histories of delinquency and substance use predict strangers' perceptions of young men's facial trustworthiness. Methods: Boys (n = 206) recruited from schools with higher juvenile crime rates were assessed repeatedly from ages 10–24 years, including arrest records and self-reported delinquency and substance use. Coders blind to the study's purpose rated participants' facial trustworthiness from photographs taken at ages 14 and 24; parent-reported childhood family income and coder ratings of attractiveness and positive affect at age 24 were considered as controls. Results: Facial trustworthiness at age 24 (but not age 14) negatively correlated with all measures of problem behavior. Yet, self-reported tobacco use occasions from ages 12–23 had the strongest association with facial trustworthiness at age 24, a relation that persisted when controlling for arrests and delinquency from ages 12–23, other substance use, family income, ratings of age-24 positive facial affect, attractiveness, and age-14 facial trustworthiness (β = −.29, 95% CI [−.42, −.15], p < .001). Discussion: Although boys' early facial trustworthiness did not relate to their later problem behavior, men with histories of more delinquency and tobacco use appeared less facially trustworthy as adults. Appearance-related biases may have forensic and healthcare implications for young men. Additionally, prevention efforts could leverage information about the early impacts of tobacco use on appearance.
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Ageing is a natural phenomenon which is a fold, ridge and crease in the skin that occurs due to loss of body mass, poor hydration, disintegration of dermis and epidermis junction. The Skin ageing process involves many changes that occur due to the combination of both endogenous factors (gene mutation, cellular metabolism, and hormonal factor) and exogenous factors (U.V, pollutants, chemical, and toxins). In 1950, the number of older people were found to be almost 205 million across the globe. But this number almost got 4 times by the year 2012 and the number of older persons increased to a massive amount of 810 million. The ageing of the skin occurs due to various mechanisms like glycation, free radical, cell cycle, cellular and molecular mechanism of skin ageing. In this review article, we have discussed about the treatment, worldwide newer therapies and marketed formulation that is currently available for the reduction of skin ageing. The most promising and revolutionizing field of nanotechnology is mostly applied in the field of dermatology, cosmetics, and biomedical applications. Nanotechnology also plays a vital role in increasing the efficacy of the product.
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Stem cells provide a sensitive model to study exposure to toxicants, such as cigarette smoke. Electronic cigarettes (ECs) are popular nicotine delivery devices, often targeted to youth and pregnant mothers. However, little is known about how chemicals in ECs might affect neural stem cells, and in particular their mitochondria, organelles that maintain cell functionality and health. Here we show that the mechanism underlying EC-induced stem cell toxicity is stress-induced mitochondrial hyperfusion (SIMH), a transient survival response accompanied by increased mitochondrial oxidative stress. We identify SIMH as a survival response to nicotine, now widely available in EC refill fluids and in pure form for do-it-yourself EC products. These observed mitochondrial alterations combined with autophagy dysfunction to clear damaged mitochondria could lead to faulty stem cell populations, accelerate cellular aging, and lead to acquired mitochondriopathies. Any nicotine-containing product may likewise stress stem cells with long-term repercussions for users and passively exposed individuals. Video Abstract: : Medicine; Smoking; Cell Biology; Stem Cells Research; Biological Sciences Research Methodologies Subject Areas: Medicine, Smoking, Cell Biology, Stem Cells Research, Biological Sciences Research Methodologies
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Over the past decade, there has been a surge in demand for minimally invasive treatments for aging skin. Patients seek non-surgical treatments due to reduced procedure-associated risks and faster recovery time compared to traditional surgical methods. One component of aging skin is the appearance of laxity, which is due to thinning of the epidermis, loss of dermal connective tissue and atrophy and/or redistribution of subcutaneous fat, or all of the above. Innovation in energy-based devices has created multiple avenues to address the various factors leading to skin laxity. This chapter will discuss the mechanism of action, efficacy and safety of ablative and non-ablative lasers, infrared light, ultrasound, and microneedling in treatment of skin laxity.
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Background Facial aging is a process that involves many different changes. Therefore, in many patients, it may be necessary to perform a combined treatment. Botulinum toxin A and dermal fillers are the two most popular nonsurgical cosmetic procedures performed globally to treat age-associated changes. However, there are not many studies reporting the concomitant use of dermal fillers and laser technology for facial rejuvenation. This review aims to assess the concomitant use of dermal hyaluronic acid (HA) fillers and laser technology for facial rejuvenation. Methods The present updated consensus recommendations are based on the experience and opinions of the authors and on a literature search. Results If a combined procedure (HA and light treatments) is to be performed, on the same day, the panel recommends starting always with the light treatments, avoiding skin manipulations after having injected HA. To customize the therapeutic management, it is crucial to establish a precise diagnosis of the photodamage and loss of volumes suffered by the patients. Conclusions The currently available scientific evidence about the combined use of HA fillers and laser–radiofrequency–intense pulsed light (laser/RF/IPL) is limited and encompasses mainly small and nonrandomized studies. Nevertheless, most of these studies found that, on average, the concomitant use (same day) of laser and HA fillers for facial rejuvenation represents an effective and safe strategy which improves clinical results and patient’s satisfaction. Future well-designed clinical studies are needed regarding the effectiveness and safety of combination filler/laser treatments. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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More than a barrier against environmental agents, skin reflects individual health and is a visible sign of ageing with the progressive loss of skin integrity. In order to evaluate the consequences of an environmental complex mixture, with tobacco smoke (TS) as model, on cellular and morphological changes, a 3D skin model was used. Morphologically, tissue integrity was intact after one TS-exposure while the superficial layers were drastically reduced after two TS-exposures. However, TS modified epidermal organisation at the molecular level after just one exposure. A decrease in loricrin protein staining was showed in the epidermis, while production of inflammatory cytokines (IL-8, IL-1α, IL-18) and metalloproteinase (MMP-1, MMP-3) were stimulated. Oxidative stress was also illustrated with an increase in 4-HNE protein staining. Moreover, terminal differentiation, cell-cell junction and anchorage gene expression was down-regulated in our model after one TS-exposure. In conclusion, tobacco smoke impacted the fundamental functions of skin, namely tissue anchorage, cornification and skin desquamation. Oxidative stress resulted in skin ageing. The tissue was even reactive with the inflammatory pathways, after one TS-exposure. The 3D-RHE model is appropriate for evaluating the impact of environmental pollutants on skin ageing.
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The small proteoglycans (PG) of bone consist of two different molecular species: one containing one chondroitin sulfate chain (PG II) and the other, two chains (PG I). These two proteoglycans are found in many connective tissues and have Mr = 45,000 core proteins with clear differences in their NH2-terminal sequences. Using antisera produced against synthetic peptides derived from the human PG I and PG II NH2 termini, we have isolated several cDNA clones from a lambda gt11 expression library made against mRNA isolated from human bone-derived cells. The clones, which reacted with antisera to the PG II peptide, were sequenced and found to be identical with the PG II class of proteoglycan from human fibroblasts known as PG-40 or decorin. The clones reacting to the PG I antisera, however, had a unique sequence. The derived protein sequence of PG I showed sufficient homology with the PG II sequence (55% of the amino acids are identical, with most others involving chemically similar amino acid substitutions) to strongly suggest that the two proteins were the result of a gene duplication. PG II (decorin) contains one attached glycosaminoglycan chain, while PG I probably contains two chains. For this reason, we suggest that PG I be called biglycan. The biglycan protein sequence contains 368 residues (Mr = 42,510 for the complete sequence and Mr = 37,983 for the secreted form) that appears to consist predominantly of a series of 12 tandem repeats of 24 residues. The repeats are recognized by their conserved leucines (and leucine-like amino acids) in positions previously reported for a diverse collection of proteins (none of which is thought to be proteoglycans) including: two morphogenic proteins (toll and chaoptin) in the fruit fly; a yeast adenylate cyclase; and two human proteins, the von Willebrand Factor-binding platelet membrane protein, GPIb, and a rare serum protein, leucine-rich glycoprotein.
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This study examined the association of smoking status and pack-years of smoking with facial wrinkling in men and women. We conducted a cross-sectional study of 299 never smokers, 551 former smokers and 286 current smokers, aged 30 through 69 years, drawn from a health maintenance organization. Smoking status, pack-years of smoking, and potential confounding variables were assessed by questionnaire. Facial wrinkle category, a dichotomous variable, and facial wrinkle score, a computed continuous variable, were assessed by blinded standardized visual assessment. Wrinkling was so uncommon among 30- through 39-year-old subjects that analyses were restricted to subjects aged 40 and over (227 never smokers, 456 former smokers, and 228 current smokers). With age, average sun exposure, and body mass index controlled, the estimated relative risk of moderate/severe wrinkling for current smokers compared to never smokers was 2.3 (95% confidence interval [CI] = 1.2, 4.2) among men and 3.1 (95% CI = 1.6, 5.9) among women. Pack-years was positively associated with facial wrinkle score in women aged 40 through 69 years and in men aged 40 through 59 years. In both groups, the increased risk of wrinkling was equivalent to about 1.4 years of aging. Our results support earlier findings that risk of facial wrinkling is greater in cigarette smokers than in never smokers.
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Ki-1 (CD30)+ cutaneous T-cell lymphomas CTCLs) are slowly progressive lymphomas in which initial spontaneous regression is often observed. To better understand the mechanisms of spontaneous regression and eventual tumor progression in Ki-1+ CTCLs, type beta transforming growth factor (TGF-beta)-mediated growth inhibition of clonally related cell lines derived from two time points, before and after tumor progression, was studied. TGF-beta 1 inhibited colony-forming efficiency (CFE) of a cell line (Mac-1) derived from clinically indolent Ki-1+ CTCLs but failed to inhibit CFE of Mac-2A and -2B cell lines from advanced CTCLs. To determine the basis for TGF-beta 1 resistance in advanced CTCL cells, we looked for possible defects in the expression of cell surface TGF-beta receptors. Mac-1 cells were found to express TGF-beta receptors I and II, which mediate growth inhibition, and the TGF-beta-binding proteoglycan betaglycan. In contrast, receptors I and II were not detected in CTCL lines Mac-2A and -2B even though these cell lines did express betaglycan. Various treatments that unmask or induce TGF-beta receptors in other cells failed to show evidence for these receptors in advanced CTCL cells. Loss of TGF-beta receptor expression in these cells correlated with a marked decrease in TGF-beta receptor II mRNA levels. Loss of cell surface TGF-beta receptors was also found in two of five other patients with T-cell lymphomas including the Sezary syndrome and a noncutaneous T-cell lymphoma, suggesting that loss of TGF-beta receptor expression may be a recurrent feature of human T-cell malignancies.
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Decorin is a member of the expanding group of widely distributed small leucine-rich proteoglycans that are expected to play important functions in tissue assembly. We report that mice harboring a targeted disruption of the decorin gene are viable but have fragile skin with markedly reduced tensile strength. Ultrastructural analysis revealed abnormal collagen morphology in skin and tendon, with coarser and irregular fiber outlines. Quantitative scanning transmission EM of individual collagen fibrils showed abrupt increases and decreases in mass along their axes. thereby accounting for the irregular outlines and size variability observed in cross-sections. The data indicate uncontrolled lateral fusion of collagen fibrils in the decorindeficient mice and provide an explanation for the reduced tensile strength of the skin. These findings demonstrate a fundamental role for decorin in regulating collagen fiber formation in vivo.
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Transforming growth factor-beta (TGF-beta) superfamily members are multifunctional cell-cell signaling proteins that play pivotal roles in tissue homeostasis and development of multicellular animals. They mediate their pleiotropic effects from membrane to nucleus through distinct combinations of type I and type II serine/threonine kinase receptors and their downstream effectors, known as Smad proteins. Certain Smads, termed receptor-regulated Smads, become phosphorylated by activated type I receptors and form heteromeric complexes with a common-partner Smad4, which translocates into the nucleus to control gene transcription. In addition to these signal transducing Smads, inhibitory Smads have been identified that inhibit the activation of receptor-regulated Smads. In contrast to the still growing TGF-beta superfamily (with approximately 30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recent insights into the molecular mechanisms by which signaling specificity between different TGF-beta superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses.-Piek, E., Heldin, C.-H., ten Dijke, P. Specificity, diversity, and regulation in TGF-beta superfamily signaling.
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Aging of the skin has fascinated researchers for decades not only to ultimately prevent wrinkle formation, but also because the skin represents an excellent and accessible model organ allowing the study of intrinsic and extrinsic factors coordinately contributing to the complex phenomenon of aging. Basic principles underlying skin aging are thought to have general relevance for common degenerative connective-tissue diseases like oste-oarthritis, osteoporosis and arteriosclerosis [1]. Chronological (intrinsic) aging affects the skin in a manner similar to that of other organs [2]. Superimposed on this innate process, extrinsic aging is related to environmental , mainly UV-induced damage of the dermal connective tissue. There is evidence that these processes, intrinsic and extrinsic aging, have at least in part overlapping, biological, biochemical and molecular mechanisms [3]. Cellular changes as well as qualitative and quantitative alterations of dermal extracellular matrix proteins are involved, resulting in loss of recoil capacity and tensile strength with wrinkle formation, increased fragility and impaired wound healing. UVB (280–320 nm) and UVA (320–400 nm) are essential components of sunlight that generate severe oxidative stress in skin cells via interaction with intracellular chromophores and photosensitizers, resulting in transient and permanent genetic damage, and in the activation of cyto-plasmic signal transduction pathways that are related to growth, differentiation , replicative senescence and connective-tissue degradation. In this review, we will discuss photoaging as related to its morphological phenotype and underlying mechanisms.
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Transforming growth factor-beta (TGF-beta) is a multi-functional cytokine that regulates cell growth and differentiation. Cellular responses to TGF-beta are mediated through its cell surface receptor complex, which activates transcription factors Smad2 and Smad3. Here we report that UV irradiation of mink lung epithelial cells causes near complete inhibition of TGF-beta-induced Smad2/3-mediated gene expression. UV irradiation inhibited TGF-beta-induced phosphorylation of Smad2 and subsequent nuclear translocation and DNA binding of Smad2/3. Specific cell surface binding of TGF-beta was substantially reduced after UV irradiation. This loss of TGF-beta binding resulted from UV-induced down-regulation of TGF-beta type II receptor (T beta RII) mRNA and protein. UV irradiation significantly inhibited T beta RII promoter reporter constructs, indicating that UV reduction of T beta RII expression involved transcriptional repression. In contrast to its effects on T beta RII, UV irradiation rapidly induced Smad7 mRNA and protein. Smad7 is known to antagonize activation of Smad2/3 and thereby block TGF-beta-dependent gene expression. UV irradiation stimulated Smad7 promoter reporter constructs, indicating that increased Smad7 expression resulted, at least in part, from increased transcription. Overexpression of Smad7 protein to the level induced by UV irradiation inhibited TGF-beta-induced gene expression 30%. Maintaining T beta RII levels by overexpression of T beta RII prevented UV inhibition of TGF-beta responsiveness. Taken together, these data indicate that UV irradiation blocks cellular responsiveness to TGF-beta through two mechanisms that impair TGF-beta receptor function. The primary mechanism is down-regulation of T beta RII, and the secondary mechanism is induction of Smad7.
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Cigarette smoking is the single biggest preventable cause of death and disability in developed countries and is a significant public health concern. While known to be strongly associated with a number of cardiovascular and pulmonary diseases and cancers, smoking also leads to a variety of cutaneous manifestations. This article reviews the effects of cigarette smoking on the skin and its appendages. A literature review was based on a MEDLINE search (1966-2004) for English-language articles using the MeSH terms cutaneous, dermatology, tobacco, skin, and smoking. An additional search was subsequently undertaken for articles related to smoking and associated mucocutanous diseases, with the focus on pathogenesis and epidemiologic data. Articles presenting the highest level of evidence and latest reports were preferentially selected. Smoking is strongly associated with numerous dermatologic conditions including poor wound healing, wrinkling and premature skin aging, squamous cell carcinoma, psoriasis, hidradenitis suppurativa, hair loss, oral cancers, and other oral conditions. In addition, it has an impact on the skin lesions observed in diabetes, lupus, and AIDS. The evidence linking smoking and melanoma, eczema, and acne is inconclusive. Anecdotal data exist on the possible protective effects of smoking in oral/genital aphthosis of Behçet's disease, herpes labialis, pyoderma gangrenosum, acral melanoma, and Kaposi's sarcoma in AIDS patients. An appreciation of the adverse cutaneous consequences of smoking is important. Dermatologists can play an integral role in promoting smoking cessation by providing expert opinion and educating the public on the deleterious effects of smoking on the skin.
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Transforming growth factor-beta (TGF-beta) superfamily members are multifunctional cell-cell signaling proteins that play pivotal roles in tissue homeostasis and development of multicellular animals. They mediate their pleiotropic effects from membrane to nucleus through distinct combinations of type I and type II serine/threonine kinase receptors and their downstream effectors, known as Smad proteins. Certain Smads, termed receptor-regulated Smads, become phosphorylated by activated type I receptors and form heteromeric complexes with a common-partner Smad4, which translocates into the nucleus to control gene transcription. In addition to these signal transducing Smads, inhibitory Smads have been identified that inhibit the activation of receptor-regulated Smads. In contrast to the still growing TGF-beta superfamily (with approximately 30 members in mammals), relatively few type I and type II receptors as well as Smads have been identified. We will focus on recent insights into the molecular mechanisms by which signaling specificity between different TGF-beta superfamily members is achieved and regulated, and how a single family member can elicit a broad scala of biological responses.-Piek, E., Heldin, C.-H., ten Dijke, P. Specificity, diversity, and regulation in TGF-beta superfamily signaling.
Article
Cigarette smoking is strongly linked to serious internal diseases such as cancer, cardiovascular disease, and lung disease. However, the external manifestations and consequences of smoking are relatively unknown. Although generally less ominous, the cutaneous manifestations of smoking may be associated with significant morbidity. This article reviews the known adverse effects on the skin of smoking.
Article
Background A numberofepidemiologic studies havesug- gested that every yearenvironmental tobacco smoke(second- handsmoke) isresponsible fortensofthousands ofdeaths, mostly fromheart disease, intheUnited States. Environmen- taltobacco smokeiscomposed mainly (80%to85%)ofaged anddiluted sidestream smoke. Theremainder isexhaled mainstream smoke. Amongthethousands ofcompounds that havebeenidentified inenvironmental tobacco smokearea number ofcarcinogens, including polynuclear aromatic hydro- carbon carcinogens, suchasbenzo(a)pyrene. Wehavedemon- strated previously thata numberofcarcinogens, including benzo(a)pyrene, promote plaque development after injection into cockerels. Therehavebeenalmost nostudies showing a direct stimulatory effect ofenvironmental tobacco smokeon plaque development. Recently wedemonstrated that cockerels exposed tosidestream smokeforapproximately 0.4%oftheir projected lifespan exhibited accelerated development ofarte- riosclerotic plaques.6 Inthatstudy, cockerels inspecially designed inhalation chambers wereexposed tothesteady-state sidestream smoke from5cigarettes for6h/dfor16weeks. This level ofexposure ishigh butenvironmentally plausible. Statis- D_ uring thepastdecade there hasbeenagrowing public perception thatinvoluntary exposure toenvironmental tobacco smoke("second- handsmoke") canresult inanincreased, ifpoorly defined, health hazard. Numerous governmental offices aswell asprivate establishments haveseverely restricted theareaswheresmoking isstill permitted orhave banned smoking entirely. Epidemiologic datahavelent support tothepublic perceptions ofthedangers posed byenvironmental tobacco smoke. TheAmerican Heart Association inarecent position paperrecommended thatenvironmental tobacco smokebeclassified asan environmental poison anddescribed itasamajorpre- ventable causeofcardiovascular disease.' Epidemio- logic studies haveattributed thousands ofexcess heart disease deaths yearly toinvoluntary exposure toenvi- ronmental tobacco smoke.2-4 However, unlike lung can- cer, wherepathophysiological alterations resulting from voluntary inhalation ofmainstream cigarette smoke havebeenwelldocumented, studies inwhich cardiovas-
Article
Proteoglycans were localized immunohistochemically in the dermis of Donryu rats, using monoclonal antibodies raised against large proteoglycan (PG-M/versican) and small proteoglycan (decorin). The localizations of these proteoglycans in the dermis were compared between young rats (22-day old) and old ones (24 or 30 months of age), and distinct age differences were observed In the young dermis, PG-M/versican was observed to be abundant in almost all fibroblastic cells (both cytoplasm and cell processes) whose cellularity was very rich compared with the dermis of old rats. Decorin was only faintly visible in the interstitial fibrous elements of young dermis. In the old dermis, however, decorin was distinctly detected on the fibrous elements, which were diffusely distributed as a fibrous network, and likewise PG-M/versican was visible in only a few fibrous elements which seemed to be the fine processes of fibroblastic cells. In the border layer between epidermis and dermis as well as the basal layer surrounding hair follicles, both large and small proteoglycans could be observed in old dermis. Since decorin, which was abundant in old dermis, has been found to have a growth inhibitory effect, it is conceivable that decorin may be one of the Cell Growth Inhibitory Factors in aging as proposed by Tauchi et al. [17 18].
Article
Background: Tobacco smoking, similar to ultraviolet (UV) A radiation exposure, has previously been identified as an important factor contributing to premature aging of human skin. To investigate the relationship between these two environmental factors, we have conducted a cross-sectional study of 83 subjects (48 males, 35 females, age range 23–95), in which sun exposure, pack-years of smoking history and potential confounding variables were assessed by questionnaire. Facial wrinkles were quantified using the Daniell score. In order to study the molecular mechanism by which smoking caused wrinkle formation, in vitro studies were conducted to assess the alteration of matrix metalloproteinase-1 (MMP-1) mRNA expression in human fibroblasts stimulated with tobacco smoke extract or/and UVA. Results: Logistic statistic analysis of the data revealed that age [odds ratio (OR)=7.5, 95% confidence interval (CI)=1.87–30.16], pack-years (OR=5.8, 95% CI=1.72–19.87), and sun exposure (OR=2.65, 95% CI=1.0–7.0) independently contributed to facial wrinkle formation. When excessive sun exposure (>2 h/day) and heavy smoking (35 pack-years) occurred together, the risk for developing wrinkles was 11.4 times higher than that of non-smokers and those with less sun exposure (<2 h/day) at the same age. The in vitro studies revealed that MMP-1 expression was significantly increased in fibroblasts after the stimulation with either tobacco smoke extract or UVA. Maximum induction was observed when cells were treated with tobacco smoke extract plus UVA, indicating that the two factors act in an additive manner. MMP-1 induction was significantly higher in the low glutathione (GSH) content fibroblast compared to that in the high GSH fibroblast, indicating that the differences in glutathione content define the susceptibility of fibroblasts towards UV- or tobacco smoking-induced MMP-1 expression. Conclusion: Tobacco smoke and UVA cause wrinkle formation independently of each other. We propose that both factors cause aging of human skin through additive induction of MMP-1 expression.
Article
This article seeks to explore the relationship between the European Union (EU) and the changing European order, with particular respect to the ways in which the EU structures and shapes the boundaries between itself and the broader European arena. It evaluates a range of available international relations theories, and adopts a 'critical neoliberal-institutionalist' approach to the problem. It applies this approach by assessing the EU's boundary-constructing and boundary-maintaining behaviour in a number of areas, before developing two models of the EU's role: the 'politics of exclusion' and the 'politics of inclusion'. After spending most of its life practising the 'politics of exclusion', the EU has moved towards a 'politics of inclusion' to reflect the changing demands of the European order. Nevertheless, the tensions between the two types of politics will continue to be a central feature of the EU's role. Copyright 1996 BPL.
Article
During the last 20 years, at least five studies have examined the association between cigarette smoking and facial wrinkling. Although there are methodological concerns with each of these studies, the data are consistent with the conclusion that smoking causes skin wrinkling that could make smokers appear unattractive and prematurely old. Cigarette smoking has been shown to decrease capillary and arteriolar blood flow in the skin, perhaps damaging connective tissue components that are important to maintaining the integrity of the skin. Americans are highly motivated to avoid or eliminate facial wrinkles. The association of smoking and facial wrinkling may be important evidence to convince young persons not to begin smoking and older smokers to quit.
Article
To determine if cigarette smoking is a risk factor for the development of premature facial wrinkling. Cross-sectional study. Smoking cessation clinic and community. Convenience sample of 132 adult smokers and non-smokers in 1988. A questionnaire was administered to quantify cigarette smoking and to obtain information about possibly confounding factors such as skin pigmentation, sun exposure, age, and sex. Wrinkling was assessed using photographs of the temple region, and a severity score based on predetermined criteria was assigned. A logistic regression model, which controlled for confounding variables, was developed to assess the risk for premature wrinkling in response to pack-years of smoking. The prevalence of premature wrinkling was independently associated with sun exposure and pack-years of smoking. After controlling for age, sex, and sun exposure, premature wrinkling increased with increased pack-years of smoking. Heavy cigarette smokers (greater than 50 pack-years) were 4.7 times more likely to be wrinkled than nonsmokers (95% CI, 1.0 to 22.6; P value for trend = 0.05). Sun exposure of more than 50,000 lifetime hours also increased the risk of being excessively wrinkled 3.1-fold (CI, 1.2 to 7.1). When excessive sun exposure and cigarette smoking occurred together, the risk for developing excessive wrinkling was multiplicative (prevalence ratio of 12.0; CI, 1.5 to 530). Cigarette smoking is an independent risk factor for the development of premature wrinkling.
Article
The primary structure of a large chondroitin sulfate proteoglycan expressed by human fibroblasts has been determined. Overlapping cDNA clones code for the entire 2389 amino acid long core protein and the 20-residue signal peptide. The sequence predicts a potential hyaluronic acid-binding domain in the amino-terminal portion. This domain contains sequences virtually identical to partial peptide sequences from a glial hyaluronate-binding protein. Putative glycosaminoglycan attachment sites are located in the middle of the protein. The carboxy-terminal portion includes two epidermal growth factor (EGF)-like repeats, a lectin-like sequence and a complement regulatory protein-like domain. The same set of binding elements has also been identified in a new class of cell adhesion molecules. Amino- and carboxy-terminal portions of the fibroblast core protein are closely related to the core protein of a large chondroitin sulfate proteoglycan of chondrosarcoma cells. However, the glycosaminoglycan attachment regions in the middle of the core proteins are different and only the fibroblast core protein contains EGF-like repeats. Based on the similarities of its domains with various binding elements of other proteins, we suggest that the large fibroblast proteoglycan, herein referred to as versican, may function in cell recognition, possibly by connecting extracellular matrix components and cell surface glycoproteins.
Article
Tobacco smoke contains numerous compounds emitted as gases and condensed tar particles. The sidestream smoke emissions, which constitute the major part of environmental tobacco smoke (ETS), are generally larger than the mainstream smoke emissions. Many of the organic compounds, belonging to a variety of chemical classes, are known to be genotoxic and carcinogenic. These include the known constituents, alkenes, nitrosamines, aromatic and heterocyclic hydrocarbons and amines. Emission of sidestream smoke in indoor environments with relatively low ventilation rates can result in pollutant concentrations above those generally encountered in ambient air in urban areas. The chemical characteristics of ETS thus support the indications that exposure to ETS can be causally associated with the induction of several types of cancer.
Article
Clinically detectable, age-associated cutaneous changes result from two independent processes: chronologic aging and actinic irradiation. Several lines of evidence suggest that these two processes have different biologic, biochemical, and molecular mechanisms. This review summarizes the current understanding of age-associated alterations in the biochemistry and molecular biology of the extracellular matrix.
Article
In glycomethacrylate sections of sun-exposed skin, we found the epidermis a sensitive index of damage. The stratum corneum of severely damaged skin was often compact and laminated, or gelatinous, and sometimes contained vesicles full of proteinous material. These vesicles arose from the enlarged and distinctly cellular-thick stratum lucidum. Sometimes there was no clear transition between the stratum lucidum and corneum. In the malpighian layer, cell heterogeneity, vacuolization, dysplasia, and zonal necrosis were common. The number of Langerhans cells was reduced in sun-damaged epidermis. The dermis had the usual disparate degrees of elastotic changes, with the formation of amorphous masses and the occurrence of fiber breakdown (fibrorhexis and fibrolysis). Macrophages among the elastotic masses contained coarse granules. When stained by means of the hematoxylin and Lee technique, the elastotic masses in the papillary dermis were pink or red but those in the mid dermis stained lilac to blue; all other elastic fibers stained pink or red. We found reticulin fibers predominantly around the elastotic masses and in areas of fibrorhexis and/or fibrolysis; a delicate collagenous fiber scaffolding supported the elastotic masses.
Article
Deep wrinkles of 6 elderly people were investigated using electron microscopy. There were ultrastructural differences in the elastotic changes between the area of the wrinkle and the surrounding areas. Elastic fibers containing electron-dense inclusions were mostly seen in the upper dermis of the wrinkled area and were considered to be an early event of the elastotic changes. The elastotic changes showing net-like structures were seen in the areas surrounding the wrinkle and were considered to be a more advanced event. Another form of elastotic change was the presence of thickened elastic fibers with many holes containing round bodies, which were scattered in the deep dermis of the wrinkled area, and increased and packed in the middle and deep dermis of the surrounding areas. In one case subepidermal amyloid deposits were seen in the areas surrounding the wrinkle, suggesting a close relationship between amyloid and sun-light exposure.
Article
Mice were treated with several different potentially carcinogenic components of tobacco smoke. The chemicals used were: 4-aminobiphenyl and aniline-HCl, which are found in high concentrations in sidestream tobacco smoke; hydrazine sulfate, which is found in high concentrations in mainstream tobacco smoke; and 2-methylquinoline, which is found in intermediate concentrations in both sidestream and mainstream smoke. The chemicals were injected i.p. into mice, and then alpha/beta interferon was induced in the mice by i.v. injection of polyriboinosinic-polyribocytidylic acid. The interferon was induced either 2, 24, or 48 hr after treatment with the tobacco smoke components. Mice treated with 4-aminobiphenyl showed some depression of interferon production 2 hr after treatment, maximum inhibition of interferon induction 24 hr after treatment, and a return to control levels of interferon 48 hr after treatment. Mice treated with hydrazine sulfate showed maximum inhibition of interferon induction 24 hr after treatment but no effects at any other treatment time. These components were the most carcinogenic chemicals of those utilized in this study. Treatment of mice with aniline-HCl, a chemical whose carcinogenic potential is still debated, resulted in marginal depression of interferon induction 24 hr after treatment. 2-Methylquinoline, the chemical with the lowest carcinogenic potential in this study, had no effect on interferon induction after administration to mice. In vivo interferon induction was, therefore, inhibited by treatment of mice with chemical carcinogens found in tobacco smoke. The efficacy of the chemical in inhibiting interferon induction was not influenced by the mainstream or sidestream smoke predominance of the chemical.
Article
Chronic sun exposure induces numerous changes in exposed skin; the most striking histopathologic change is the massive accumulation of material with the staining characteristics of elastin, termed solar elastosis, in the superficial dermis. Previous studies have identified elastic fibers within areas of solar elastosis, as well as a decrease in collagen content. Recently, the large chondroitin sulfate (CS) proteoglycan, versican, has been identified in the dermis in association with elastic fibers, and the smaller CS proteoglycan, decorin, has been shown to codistribute with collagen fibers. Thus, changes in expression of these CS proteoglycans might be expected in photoaging and may help to explain the clinical alterations of chronically sun-exposed skin. Immunohistochemical staining and confocal laser scanning microscopy for versican and decorin was performed on paired tissue samples from photoaged and non-sun-exposed skin taken from the same individuals. To investigate versican and decorin mRNA expression, Northern analysis was performed on paired fibroblast cultures derived from tissue explants of photoaged and non-sun-exposed skin. Immunohistochemical staining and confocal laser scanning microscopy revealed a massive accumulation of versican localized to the abnormally large fibers comprising solar elastosis in the superficial and mid-dermis of photoaged specimens. Decorin staining was greatly decreased within the area of solar elastosis. Similarly, changes in mRNA were measured from fibroblast cultures, with a significant increase in versican mRNA in cultures derived from photoaged skin, whereas decorin mRNA levels were significantly decreased in photoaged skin. This study provides further evidence for the close association of versican with elastic fibers and decorin with collagen fibers, even in the situation of abnormal fiber deposition occurring in photodamaged skin. In addition, changes in versican and decorin immunostaining are accompanied by similar alterations in gene expression.
Article
A number of epidemiologic studies have suggested that every year environmental tobacco smoke (second-hand smoke) is responsible for tens of thousands of deaths, mostly from heart disease, in the United States. Environmental tobacco smoke is composed mainly (80% to 85%) of aged and diluted sidestream smoke. The remainder is exhaled mainstream smoke. Among the thousands of compounds that have been identified in environmental tobacco smoke are a number of carcinogens, including polynuclear aromatic hydrocarbon carcinogens, such as benzo(a)pyrene. We have demonstrated previously that a number of carcinogens, including benzo(a)pyrene, promote plaque development after injection into cockerels. There have been almost no studies showing a direct stimulatory effect of environmental tobacco smoke on plaque development. Recently we demonstrated that cockerels exposed to sidestream smoke for approximately 0.4% of their projected lifespan exhibited accelerated development of arteriosclerotic plaques. In that study, cockerels in specially designed inhalation chambers were exposed to the steady-state sidestream smoke from 5 cigarettes for 6 h/d for 16 weeks. This level of exposure is high but environmentally plausible. Statistically significant increases in plaque size were demonstrated in the smoke-exposed cockerels. In the present study, exposure levels were decreased by a factor of 5. Thirty cockerels were exposed to the steady-state sidestream smoke from 1 cigarette for 6 hours per day for 16 weeks. The smoke was mixed with filtered air. Ten control cockerels were exposed to filtered air only. Levels of smoke surrogates, including carbon monoxide and total suspended particulates, were measured three times a day. Again, there was a statistically significant increase in plaque size in the smoke-exposed cockerels. To place these studies within a context of environmental relevance, levels of carbon monoxide were measured independently over 1 to 3 hours in four bars where there was heavy smoking. Measured carbon monoxide levels were as high or higher in the bars than they were in the exposure chambers during the 1-cigarette sidestream-smoke study. Experimental exposure to secondhand smoke at levels equal to or even below those routinely encountered by people in smoke-filled environments is sufficient to promote arteriosclerotic plaque development.
Article
Abstract— The effect of UVB exposure on the distribution and synthesis of dermal proteoglycans was measured in the skin of hairless mice. Two groups of mice were included: one was irradiated for 10 weeks; the other was kept as control. After intraperitoneal injection of sodium 35S-sulfate, punch biopsies were taken for histology and proteoglycans were extracted from the remaining skin with 4 M guanidinium chloride, containing 3–[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (0.5%, weight per volume). Following proteolytic digestion, the glycosaminoglycan constituents were isolated and analyzed by quantitative cellulose acetate electrophoresis and enzymatic digestibility. Under the influence of UVB radiation, newly synthesized proteoglycans measured by 35SO4 uptake increased as much as 60%. In addition, the irradiated skin had a higher average content of proteoglycan than had control skin (4981 μg vs 4134 μg/g dry weight). This could be ascribed to an increase in heparin (1400 vs 533 μg/g dry weight) and heparan sulfate (472 vs 367 μg/g dry weight), whereas no change in the concentration of hyaluronic acid (1243 vs 1372 μg/g dry weight) and dermatan sulfate (1866 vs 1863 μg/g dry weight) was observed. The irradiated animals also exhibited a marked increase in the synthesis of heparan sulfate and heparin (62% and 71%, respectively). These results demonstrate that chronic doses of UVB altered proteoglycan metabolism through both quantitative and qualitative changes.
Article
Tobacco smoking causes a major fraction of male urinary bladder cancers and the relative risk of bladder cancer is reported to be two to three times higher for smoking of black (air-cured) than for smoking of blond (flue-cured) tobacco. In molecular dosimetry studies to examine the hypothesis that aromatic amines in tobacco smoke are primarily responsible for bladder cancer, the higher bladder cancer risk in smokers of black tobacco was correlated with two to five times higher exposure to carcinogenic aromatic amines present in black tobacco smoke, notably 4-aminobiphenyl (ABP). For the same amount of smoking, black tobacco smokers had levels of ABP-haemoglobin (Hb) adducts 1.5 times higher and excreted a 1.8-fold higher level of urinary mutagens. These mutagens were characterised as aromatic amines, and included the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a known mutagen and multiorgan/species carcinogen. In smoking volunteers, the ABP-Hb adduct level depended significantly on the acetylator and P-450IA2 phenotypes, being 1.3- to 1.5-fold lower in fast acetylators, slow/intermediate P-450IA2 individuals. The N-(deoxyguanosine-8-yl)-ABP adduct was a major smoking-related DNA adduct in bladder biopsies from surgical patients. It was also tentatively identified in exfoliated urothelial cells of smoking volunteers, who showed a significant and linear correlation between adduct levels of ABP with Hb and with deoxyguanosine in urothelial DNA; both were related to number of cigarettes smoked per day. Levels of several smoking-related DNA adducts in urothelial cells were 2-20 times elevated in smokers. Similar convex dose-response relationships have been found between the number of cigarettes smoked and the relative risk for bladder cancer and between the levels of ABP-Hb adducts and markers of recent smoking. A possible explanation is that fast and slow acetylators have different susceptibility to aromatic amine carcinogens. Case-control studies have consistently revealed an excess of variable magnitude of slow acetylators in subgroups exposed occupationally to carcinogenic aromatic amines. Altogether, results from these studies reinforce the association between cigarette smoking, carcinogen-DNA adducts in urothelial cells, and implicate primary aromatic and possibly heterocyclic amines as bladder carcinogens.
Article
Cigarette smoking is strongly linked to serious internal diseases such as cancer, cardiovascular disease, and lung disease. However, the external manifestations and consequences of smoking are relatively unknown. Although generally less ominous, the cutaneous manifestations of smoking may be associated with significant morbidity. This article reviews the known adverse effects on the skin of smoking.
Article
Smoking is a major risk factor for cardiovascular morbidity and mortality. Because previous studies have shown that smoking affects vasomotor response, we hypothesized that smoking may also acutely alter aortic elastic properties. We studied 40 male current and long-term smokers who underwent diagnostic cardiac catheterization for chest-pain evaluation. Twenty subjects (age, 48 +/- 2 years, mean +/- SEM) were randomly assigned to smoking and 20 (age, 47 +/- 2 years) to sham smoking studies. Aortic elastic properties were studied with the determination of the aortic pressure-diameter relation before smoking, every minute for the first 5 minutes after the initiation of smoking or sham smoking, and every 5 minutes for the following 15 minutes. Instantaneous diameter of the thoracic aorta was measured with a special ultrasonic dimension catheter developed in our laboratory and previously validated. Instantaneous aortic pressure was measured at the same site as was diameter with a Millar micromanometer. Smoking was associated with significant changes in the aortic pressure-diameter relation that denote deterioration of the elastic properties and were maintained during the whole study period: the slope of the pressure-diameter loop became steeper (baseline, 35.43 +/- 1.38; minute 1, 45.26 +/- 1.65; peak at minute 10, 46.36 +/- 1.69 mm Hg/mm; P < .001) and aortic distensibility decreased (baseline, 2.08 +/- 0.12; minute 1, 1.60 +/- 0.08; nadir at minute 5, 1.54 +/- 0.07 x 10(-6) cm2.dyne-1; P < .001). In contrast, no changes in aortic elasticity indexes were observed with sham smoking. Smoking is associated with an acute deterioration of aortic elastic properties. This effect of smoking may contribute to the unfavorable consequences of smoking on the cardiovascular system.
Article
Maternal smoking during pregnancy has been shown to lead to immunologic changes in the offspring. However, little is known about the influence of this exposure on atopic manifestations. Our purpose was to investigate the influence of air pollutants on manifestations of atopy in preschool children. Unselected cohorts of a total of 678 5- to 6-year-old preschool children (350 boys, 328 girls) were investigated in areas with different degrees of air pollution in Bavaria. Data on the history of atopic diseases and other relevant factors were obtained by questionnaire. A skin-prick test was performed with common aeroallergens. Manifestation of atopy was defined as personal history of atopic disease or positive prick test to either grass pollen, house dust mite, or cat and analyzed multivariately. Of all children, 38.9% exhibited at least one manifestation of atopy. Atopic eczema was reported in 7.9% to 15.5%, hayfever in 4.1% to 25.6%, and asthma in 3.0% to 8.1%. Of the mothers, 12.6% smoked during pregnancy or lactation or both. Analysis of the manifestation of atopy including sex, location, nitrogen oxide and sulfur dioxide exposure and maternal smoking as covariates revealed an influence of the maternal smoking during pregnancy/lactation. Of children whose mothers had smoked during pregnancy/lactation, 52.2% exhibited manifestations of atopy in contrast to 35.7% of children of nonsmoking mothers (p < 0.044). A history of atopic eczema was the only component of the variable "manifestation of atopy" that was significantly associated with maternal smoking during pregnancy and lactation. A causal interpretation of this finding, however, was not supported by a follow-up study. Maternal smoking during pregnancy or lactation or both might play a role in the development of atopic eczema and should be avoided.
Article
Increased gene expression as a consequence of environmental stress is typically observed in mammalian cells upon exposure to ultraviolet (UV) radiation. In previous years the cis- and trans-acting genetic elements responsible for gene induction by short wavelength UVC (< 280nm) and intermediate wavelength UVB (280 - 320 nm) radiation have been well characterized. More recently, progress has also been made in understanding the mechanisms by which long wavelength UVA (320 - 400 nm) radiation induces transcriptional activation of human genes. From these studies it is now known that the photobiological as well as the molecular mechanisms involved in UVA radiation-induced gene expression differ from those previously identified for UVB- or UVC-induced gene expression. In particular, the reactive oxygen species singlet oxygen was found to serve as the primary effector in UVA radiation-induced gene expression by inducing a signal transduction cascade that depends on activation of transcription factor AP-2. These studies indicate a previously unrecognized role of AP-2 in the mammalian stress response.
Article
Ultraviolet radiation from the sun damages human skin, resulting in an old and wrinkled appearance. A substantial amount of circumstantial evidence indicates that photoaging results in part from alterations in the composition, organization, and structure of the collagenous extracellular matrix in the dermis. This paper reviews the authors' investigations into the molecular mechanisms by which ultraviolet irradiation damages the dermal extracellular matrix and provides evidence for prevention of this damage by all-trans retinoic acid in human skin in vivo. Based on experimental evidence a working model is proposed whereby ultraviolet irradiation activates growth factor and cytokine receptors on keratinocytes and dermal cells, resulting in downstream signal transduction through activation of MAP kinase pathways. These signaling pathways converge in the nucleus of cells to induce c-Jun, which heterodimerizes with constitutively expressed c-Fos to form activated complexes of the transcription factor AP-1. In the dermis and epidermis, AP-1 induces expression of matrix metalloproteinases collagenase, 92 kDa gelatinase, and stromelysin, which degrade collagen and other proteins that comprise the dermal extracellular matrix. It is hypothesized that dermal breakdown is followed by repair that, like all wound repair, is imperfect. Imperfect repair yields a deficit in the structural integrity of the dermis, a solar scar. Dermal degradation followed by imperfect repair is repeated with each intermittent exposure to ultraviolet irradiation, leading to accumulation of solar scarring, and ultimately visible photoaging. All-trans retinoic acid acts to inhibit induction of c-Jun protein by ultraviolet irradiation, thereby preventing increased matrix metalloproteinases and ensuing dermal damage.
Article
The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
Article
In societies characterized by a preoccupation with outward appearance, many people who suffer from skin aging feel somewhat persecuted by all the advertising slogans promoting the myth of eternal youth. Today, wrinkles are considered to be one of the hallmarks of skin aging. Their development is influenced by many interactive factors, such as chronological age, genetic makeup, expression of genes, solar irradiation, toxicity of the environment, nutrition, growth factors, steroid hormones, and mechanical forces. Despite the century-old description of smokers having apparently old skin, the contribution of cigarette smoking to premature wrinkling of the face has not been extensively studied and thus remains poorly understood.
Article
Solar UV radiation damages human skin, affecting skin tone and resiliency and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metalloproteinases (MMP) that degrade skin collagen. We find that pretreatment of human skin with all-trans retinoic acid (tRA) inhibits UV induction of MMP, suggesting that tRA can protect against UV-induced collagen destruction and may therefore be able to lessen the effects of photoaging. The tRA prevents UV-induced accumulation of c-Jun protein, which is required for MMP gene expression. Activation of c-Jun transcriptional activity requires N-terminal phosphorylation. The majority of c-Jun in human skin in vivo is N-terminal phosphorylated. Topically applied tRA does not inhibit N-terminal phosphorylation by UV-induced c-Jun kinase activity in human skin. The tRA likely acts to reduce UV induction of c-Jun protein by stimulating its breakdown through the ubiquitin-proteasome pathway.
Article
Clinical features of the skin in persons who smoke include increased wrinkling, gauntness, and discoloration that has been termed smoker's face. The histologic changes in the sun-exposed skin of these patients have not been previously elucidated. The purpose of this study was to assess the amount of elastosis in the sun-exposed skin of smokers and nonsmokers. We evaluated the skin from the forehead and cheeks of 17 smokers and 14 nonsmokers for the presence of elastosis. With the use of a computer-generated analysis of tissue sections at 4 different levels, the amount of elastotic material was expressed as an average percent of the field staining for elastic tissue. Patients were also evaluated for the presence of other malignancies, arsenic and radiation exposure, and previous skin cancers. There was a significantly greater amount of elastosis (P < .05) in the skin of patients who smoked compared with those patients who did not. No significant differences were found between the 2 groups with regard to the other parameters evaluated. Cigarette smoking is associated with an increase in elastosis, which may contribute to the clinical features of "smoker's face."
Article
Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis and several matrix metalloproteinases have previously been implicated in this process. Using immunohistochemistry and in situ hybridization, we have studied the localization of two elastolytic matrix metalloproteinases, matrilysin (matrix metalloproteinase-7) and human macrophage metalloelastase (matrix metalloproteinase-12) in solar damage. Human macrophage metalloelastase protein was detected in the superficial dermis in areas of elastotic material. Matrix metalloproteinase-7 was seen in the mid-dermis in regions with less damaged elastic fibers and morphologically better preserved collagen as well as in a band-like pattern below basal keratinocytes in eight of 18 solar elastosis. In samples taken from healthy volunteers 3 d after repeated ultraviolet A or ultraviolet B photoprovocation, occasional immunopositive cells for human macrophage metalloelastase (stromal) or matrix metalloproteinase-7 (sweat gland epithelium) were detected. In samples taken 1 d after ultraviolet B exposure, however, basal keratinocytes were matrix metalloproteinase-7 immunopositive, explaining the linear immunostaining below basal keratinocytes noted particularly in ultraviolet B treated 3 d specimens. Upregulation of metalloelastase was also demonstrated in the skin of hairless mice after repeated ultraviolet exposure. In normal skin, no staining for human macrophage metalloelastase or matrix metalloproteinase-7 was observed in association with elastin. The amount of immunoreactivity for the substrates of matrix metalloproteinase-7, versican, and tenascin, was clearly increased in solar elastosis and photoprovocated skin; versican but not tenascin was detected in the same areas as matrix metalloproteinase-7. Our results suggest that both matrix metalloproteinase-7 and -12 may contribute to remodeling of elastotic areas in sun-damaged skin.
Article
Skin undergoes dramatic age-related changes in its mechanical properties, including changes in tissue hydration and resiliency. Proteoglycans are macromolecular conjugates of protein and carbohydrate (glycosaminoglycan) which are involved in these tissue properties. In order to examine whether age-related changes in skin proteoglycans may contribute to the age-related changes in the mechanical properties of skin, proteoglycans from human skin of various ages were extracted and analyzed. Samples were obtained from two different fetal ages, from mature skin, and from senescent skin. As a function of age, there is a decrease in the proportion of large chondroitin sulfate proteoglycans (versican) and a concomitant increase in the proportion of small dermatan sulfate proteoglycans (decorin). Based on reactivity with antibodies to various chondroitin sulfate epitopes, fetal versican differs from the versican found in older skin with respect to the chondroitin sulfate chains. Also, the decorin of fetal skin is slightly larger, while the decorin of older skin shows greater polydispersity in both its size and its charge to mass ratio. There are also age-related differences in the size and polydispersity of the core proteins of decorin. The most pronounced change in skin proteoglycans is the appearance in mature skin of a proteoglycan which is smaller than decorin, but which has the same amino terminal amino acid sequence as decorin. This small proteoglycan is abundant in mature skin and may be a catabolic fragment of decorin or an alternatively spliced form of decorin. In light of the known ability of decorin to influence collagen fibrillogenesis and fibril diameter, the appearance of this small decorin-related proteoglycan may have a significant effect on skin elasticity. The observation that proteoglycans in skin show dramatic age-related differences suggests that these changes may be involved in the age-related changes in the physical properties of skin.
Article
Epidemiologic studies have indicated the association between tobacco smoking and skin aging, but the exact mechanism of tobacco smoke-induced premature skin aging is currently unknown. In this study, we investigated the alterations of collagen, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human fibroblasts treated with tobacco smoke extract. Human fibroblasts were exposed to different concentrations of water-soluble extract from tobacco smoke. Human fibroblasts irradiated with ultraviolet A1 (UVA1) were used as positive controls because the mechanism of UVA1-mediated MMP expression has been well characterized. The expression of MMP and TIMP was analyzed semiquantitatively following reverse transcriptase-polymerase chain reaction. Production of type I and type III collagens was detected by Western blotting and biosynthesis of new collagen was assessed by 3H-proline incorporation. Upon treatment with tobacco smoke extract or UVA1 irradiation, the expression of MMP-1 and MMP-3 mRNA was significantly increased in a dose-dependent manner. Maximum induction was observed with 25 microl/ml tobacco smoke extract. In contrast, the expression of TIMP-1 and TIMP-3 mRNA remained unchanged. Western blotting of the supernatant revealed that type I and type III collagens were decreased as compared with untreated controls. Collagen biosynthesis was significantly reduced by 40.1% following treatment with 25 microl/ml tobacco smoke extract. Sodium azide, L-ascorbic acid and Trolox (a water-soluble vitamin E) prevented both the UVA1- and the tobacco-induced alteration of MMP-1. These observations suggest that the imbalance of connective tissue matrix components might contribute to the molecular basis for premature skin aging in smokers. They also suggest that reactive oxygen species including singlet oxygen mediate this process.
Article
Smokers look older than non-smokers of the same age. We have compared the concentrations of mRNA for matrix metalloproteinase 1 (MMP-1) in the buttock skin of smokers and non-smokers with quantitative real-time polymerase chain reactions. MMP-1 degrades collagen, which accounts for at least 70% of the dry weight of dermis. We report significantly more MMP-1 mRNA in the skin of smokers than non-smokers whereas no difference was seen for the tissue inhibitor of metalloproteinases 1 (TIMP-1) or the housekeeping gene GAPDH (glyceraldehyde-3-phosphate dehydrogenase). We suggest that smoking-induced MMP-1 might be important in the skin-ageing effects of tobacco smoking.
Article
Epidemiological studies have showed that heavy smoking causes premature skin aging. Using a silicone rubber replica combined with computerized image processing, an objective measurement of skin's topography, we investigated the association between wrinkle formation and tobacco smoking in this study. The replica analysis was used to study the changes in the surface furrows of the volar forearm in 63 volunteers. Results confirmed that the depth (Rz) and variance (Rv) of furrows were increased and lines of furrows (Rl) were decreased with age. The replica analytic results showed that Rz and Rv in subjects with a smoking history > or =35 pack-years were significantly higher than non-smokers (P<0.05). Rl in subjects with a smoking history were significantly lower than non-smokers (P<0.05). In addition, the present results gave a good correlation between the parameters from the computerized replica analysis with the clinical grading assessment of wrinkles, which further confirmed that skin replica technique is an objective and efficacious tool in evaluation of skin premature aging.
Article
We have recently shown that tobacco smoking, like ultraviolet A radiation, is an important factor contributing to premature skin aging. We found that tobacco smoke extract decreased type I and III procollagen, increased tropoelastin mRNA, and induced abnormal accumulation of proteoglycans and matrix metalloproteinase (MMP)-1 and MMP-3 in cultured skin fibroblasts. This indicated that common molecular features might underlie the premature aging of the skin induced by tobacco smoke extract, including abnormal regulation of extracellular matrix deposition through elevated MMPs, reduced collagen production, abnormal tropoelastin accumulation, and altered proteoglycans. With the exception that reactive oxygen species were mediated in the aging process, transforming growth factor (TGF)-beta1 was found to play a crucial role in the age-related alterations induced by tobacco smoke extract. Here we report that tobacco smoke extract blocks cellular responsiveness to TGF-beta1 through the induction of a non-functional latent form of TGF-beta1, and downregulation of the TGF-beta1 receptor. This paper shows the evidence for the role of tobacco smoking in skin aging and describes how modulation of TGF-beta1 levels might retard premature skin aging.
Article
There is little clear evidence of a strong association between cumulative sun exposure and skin wrinkling. Contradictory findings also exist on the association between facial wrinkling and smoking status. To identify the significant determinants of skin wrinkling in a cohort of older subjects and to assess whether skin wrinkling can be used as an objective measure of cumulative sun exposure. This study was carried out in the South Glamorgan health district, Wales, U.K., between 1988 and 1991. A random sample of 792 older subjects (60 years and over) was obtained from the Health Authority register of patients registered with general practitioners. A range of phenotypic and environmental data was collected during a home visit by interview and examination by an experienced dermatology research fellow. Skin wrinkling/ageing was assessed by examining the face, neck and dorsum of the hand and scored on a 10-point ordinal scale. Cumulative sun exposure was assessed by asking subjects to estimate their average outdoor time during each of three periods of adult life. This measure showed acceptable repeatability (r = 0.64 for estimates obtained 1.4 years apart). The response rate was 71% and the mean age of participants was 71 years. The mean +/- SD skin ageing score was 5.5 +/- 1.5. In multiple logistic regression models only age and daily cigarette consumption were significantly associated with skin ageing. Cumulative sun exposure was significant on univariable analysis but this effect was removed by adjusting for age. Smoking 20 cigarettes per day was equivalent in effect to almost 10 years of chronological ageing. Smoking is an important determinant of macroscopic skin ageing/wrinkling in older subjects. This evidence suggests that skin ageing does not clearly provide an objective measure of cumulative ultraviolet exposure, and caution should be exercised before it is used in this way. The association between smoking and wrinkling provides important information for potential use in education campaigns to reduce smoking prevalence among young people.
Cutaneous manifestations and consequences of smoking [see comments]</