Being the more apparent organ exposed to the outdoor stressors, the effect of pollution on the skin has been widely studied in the last few decades. Although UV light is known as the most aggressive stressor to which our cutaneous tissue is daily exposed, other components of the tropospheric pollution have also shown to affect skin health and functionality. Among them, ozone has been proven to be one of the most toxic due to its high reactivity with the epidermal lipids.
View Article and Find Full Text PDFSkin is one of the main targets of the outdoor stressors. Considering that pollution levels are rising progressively, it is not surprising that several cutaneous conditions have been associated with its exposure. Among the pollutants, diesel engine exhaust (DEE) represents one of the most toxic, as it is composed of a mixture of many different noxious chemicals generated during the compression cycle, for ignition rather than an electrical spark as in gasoline engines.
View Article and Find Full Text PDFThe present study investigated the effect of spray-dried algae-rosemary particles against pollution-induced damage using ex-vivo human biopsies exposed to diesel engine exhaust (DEE). For this, the complexation of hydroalcoholic rosemary extract with Chlorella (RCH) and Spirulina (RSP) protein powders was conducted. The process efficiency and concentration of rosmarinic acid (RA), carnosic acid (CA), and carnosol (CR) phenolic compounds of both products were compared.
View Article and Find Full Text PDFOzone (O) exposure has been reported to contribute to various cutaneous inflammatory conditions, such as eczema, psoriasis, rush etc. via a redox-inflammatory pathway. O is too reactive to penetrate cutaneous tissue; it interacts with lipids present in the outermost layer of skin, resulting in formation of oxidized molecules and hydrogen peroxide (HO).
View Article and Find Full Text PDFAir pollution represents one of the main risks for both environment and human health. The rapid urbanization has been leading to a continuous release of harmful manmade substances into the atmosphere which are associated to the exacerbation of several pathologies. The skin is the main barrier of our body against the external environment and it is the main target for the outdoor stressors.
View Article and Find Full Text PDFPerineural invasion is a pathologic process of neoplastic dissemination along and invading into the nerves. Perineural invasion is associated with aggressive disease and a greater likelihood of poor outcomes. In this study, 3 of 9 patients with cutaneous squamous cell carcinoma and perineural invasion exhibited poor clinical outcomes.
View Article and Find Full Text PDFThe World Health Organization estimates that 7 million people die every year due to pollution exposure. Among the different pollutants to which living organism are exposed, ozone (O) represents one of the most toxic, because its location which is the skin is one of the direct tissues exposed to the outdoor environment. Chronic exposure to outdoor stressors can alter cutaneous redox state resulting in the activation of inflammatory pathways.
View Article and Find Full Text PDFRedox Biol
July 2020
Since the skin is one of the targets of the harmful effects of environmental insults, several studies have investigated the effects of outdoor stressors on cutaneous tissue. Ozone (O), particulate matter (PM), and ultraviolet radiation (UV) have all been shown to induce skin damage through disruption of tissue redox homeostasis, resulting in the so called "OxInflammation" condition. However, few studies have explored whether these stressors can act synergistically in cutaneous tissues.
View Article and Find Full Text PDFSeveral pollutants have been shown to affect skin physiology, among which ozone (O) is one of the most toxic. Prolonged exposure to O leads to increased oxidative damage and cutaneous inflammation. The correlation between O exposure and inflammatory cutaneous conditions (atopic dermatitis, psoriasis, acne and eczema) has been already suggested, although the mechanism involved is still unclear.
View Article and Find Full Text PDFRetinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI.
View Article and Find Full Text PDFJ Invest Dermatol
February 2018
It is generally recognized that only relatively small molecular weight (typically < ∼ 500 Da) drugs can effectively permeate through intact stratum corneum. Here, we challenge this orthodoxy using a 62-nucleotide (molecular weight = 20,395 Da) RNA-based aptamer, highly specific to the human IL-23 cytokine, with picomolar activity. Results demonstrate penetration of the aptamer into freshly excised human skin using two different fluorescent labels.
View Article and Find Full Text PDFBackground: Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, the stratum corneum prevents penetration of large molecule weight proteins, including monoclonal antibodies.
View Article and Find Full Text PDFExposure to the UV component of sunlight is the principal factor leading to skin cancer development. Cyclobutane pyrimidine dimers (CPD) are considered to be the most important pre-mutagenic type of DNA damage involved in skin carcinogenesis. To better understand the biological mechanisms of UV carcinogenesis, it is critical to understand the CPD distribution between the four types of dipyrimidine sites.
View Article and Find Full Text PDFThe use of bioengineered human skin as a bioreactor to deliver therapeutic factors has a number of advantages including accessibility that allows manipulation and monitoring of genetically modified cells. We demonstrate a skin gene therapy approach that can regulate blood pressure and treat systemic hypertension by expressing atrial natriuretic peptide (ANP), a hormone able to decrease blood pressure, in bioengineered human skin equivalents (HSE). Additionally, the expression of a selectable marker gene, multidrug resistance (MDR) type 1, is linked to ANP expression on a bicistronic vector and was coexpressed in the human keratinocytes and fibroblasts of the HSE that were grafted onto immunocompromised mice.
View Article and Find Full Text PDFBackground: The skin is an easily accessible tissue with a high blood flow facilitating the distribution of secreted peptides. These features make it a very intriguing target to serve as a biofactory releasing a systemically needed factor, such as erythropoietin (EPO).
Methods: To evaluate the potential of human keratinocytes (KC) to systemically synthesize EPO, EPO-transduced KC were grafted onto immunocompromised mice and EPO secretion was followed by serum ELISA.
The ultraviolet (UV) component of sunlight is the main cause of skin cancer. More than 50% of all non-melanoma skin cancers and >90% of squamous cell carcinomas in the US carry a sunlight-induced mutation in the p53 tumor suppressor gene. These mutations have a strong tendency to occur at methylated cytosines.
View Article and Find Full Text PDFBicistronic vectors (BCV) are important tools for gene therapy applications allowing selection for increased expression of a desired gene by linking it to a selectable gene, such as the multi-drug resistance (MDR) gene. However, both the design of the BCV and the cell type to be transduced can have a strong impact on the vector performance in the target cells. To analyze which factors might influence the efficiency of BCV in achieving high gene expression levels in skin and to determine the best suited BCV for cutaneous transduction, both keratinocytes (KC) and fibroblasts (FB) were transduced with different BCV constructs, BGIM, BMIG and QGIM.
View Article and Find Full Text PDFFor gene therapy purposes, the skin is an attractive organ to target for systemic delivery of therapeutic proteins to treat systemic diseases, skin diseases, or skin cancer. To achieve long-term stable expression of a therapeutic gene in keratinocytes (KC), we have developed an approach using a bicistronic retroviral vector expressing the desired therapeutic gene linked to a selectable marker (multidrug resistant gene, MDR) that is then introduced into KC and fibroblasts (FB) to create genetically modified human skin equivalent (HSE). After grafting the HSE onto immunocompromised mice, topical colchicine treatment is used to select and enrich for genetically modified keratinocyte stem cells (KSC) that express MDR and are resistant to colchicine's antimitotic effects.
View Article and Find Full Text PDFBackground: The skin is an interesting target tissue for gene therapy applications because of its ready accessibility. One possibility would be to utilize the genetically modified skin as a biofactory secreting a systemically needed product, such as erythropoietin (EPO).
Methods: Keratinocytes (KC) and fibroblasts (FB) were transduced with a retroviral vector encoding human EPO.
Nucleotide excision repair (NER) prevents skin cancer by eliminating highly genotoxic cyclobutane pyrimidine dimers (CPDs) induced in DNA by the UVB component of sunlight. NER consists of two distinct but overlapping subpathways, i.e.
View Article and Find Full Text PDFLigation-mediated PCR was employed to quantify cyclobutane pyrimidine dimer (CPD) formation at nucleotide resolution along exon 2 of the adenine phosphoribosyltransferase (aprt) locus in Chinese hamster ovary (CHO) cells following irradiation with either UVA (340-400 nm), UVB (295-320 nm), UVC (254 nm) or simulated sunlight (SSL; lambda > 295 nm). The resulting DNA damage spectrum for each wavelength region was then aligned with the corresponding mutational spectrum generated previously in the same genetic target. The DNA sequence specificities of CPD formation induced by UVC, UVB or SSL were very similar, i.
View Article and Find Full Text PDFThe transcription-coupled nucleotide excision repair (TCNER) pathway maintains genomic stability by rapidly eliminating helix-distorting DNA adducts, such as UV-induced cyclobutane pyrimidine dimers (CPDs), specifically from the transcribed strands of active genes. DNA mismatch repair (MMR) constitutes yet another critical antimutagenic pathway that removes mispaired bases generated during semiconservative replication. It was previously reported that the human colon adenocarcinoma strains HCT116 and LoVo (bearing homozygous mutations in the MMR genes hMLH1 and hMSH2, respectively), besides manifesting hallmark phenotypes associated with defective DNA mismatch correction, are also completely deficient in TCNER of UV-induced CPDs.
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