Treatment Of Photoaged Skin Research Articles

Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs.

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

Applications of Plasma‐Rich Plasma, Exosomes, and Stem Cells in Aesthetics: A Narrative Review

ABSTRACTIntroductionPlasma‐rich plasma (PRP), exosomes, and stem cells represent promising new treatments for facial rejuvenation and to enhance other cosmetic procedures. Although these treatments are rapidly advancing, there are no universally accepted treatment protocols for their use. The goal of the following review is to describe some of the possible benefits of PRP, exosomes, and stem cells in aesthetic medicine.ResultsA review of available studies showed that potential uses of PRP include wound healing after facial surgery, facial rejuvenation, androgenetic alopecia, acne scars, striae distensae, and vitiligo. Exosomes may provide beneficial treatment for skin rejuvenation, scar reduction, hyperpigmentation, and hair growth. Stem cells show promise for androgenetic alopecia, scar improvement, and treatment of photoaged skin. These new technologies may be used alone, but are often combined with existing aesthetic treatments.ConclusionPRP, exosomes, and stem cells may play an important role in restoring youthful tissue structure and function. Interpretation of some study results is sometimes challenged by the lack of standardized treatment protocols, including routes of application and dosing. When combined with other devices and techniques, results are sometime unclear as to which treatment plays the greater role.

The role and mechanism of engineered nanovesicles derived from hair follicle mesenchymal stem cells in the treatment of UVB-induced skin photoaging.

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are effective in the treatment of skin photoaging; however, their low yield and functional decline with passage progression limit their clinical application. Cell-derived nanovesicles (CNVs) are potential alternatives that can address the limitations of EVs derived from MSCs and are conducive to clinical transformations. Hair follicle mesenchymal stem cells (HFMSCs), a type of MSCs, have demonstrated the function of repairing skin tissues; nevertheless, the efficacy of CNVs from HFMSCs (HFMSC-CNVs) in the treatment of skin photoaging remains unclear. Therefore, ultraviolet radiation B (UVB)-induced photoaging nude mice and human dermal fibroblasts (HDFs) were used as experimental models to investigate the therapeutic effects of HFMSC-CNVs in photoaging models. HFMSC-CNVs were successfully prepared using the mechanical extrusion method. UVB-induced nude mice and HDFs were used as experimental models of photoaging. Multiple approaches, including hematoxylin-eosin and Masson staining, immunohistochemistry, immunofluorescence, detection of reactive oxygen species (ROS), flow cytometry, western blotting, and other experimental methods, were combined to investigate the possible effects and mechanisms of HFMSC-CNVs in the treatment of skin photoaging. In the nude mouse model of skin photoaging, treatment with HFMSC-CNVs reduced UVB-induced skin wrinkles (p < 0.05) and subcutaneous capillary dilation, alleviated epidermis thickening (p < 0.001), and dermal thinning (p < 0.001). Furthermore, HFMSC-CNVs upregulated proliferating cell nuclear antigen (PCNA) expression (p < 0.05) and decreased the levels of ROS, β-galactosidase (β-Gal), and CD86 (p < 0.01). Invitro experiments, treatment with HFMSC-CNVs enhanced the cellular activity of UVB-exposed HDFs (p < 0.05), and reduced ROS levels and the percentage of senescent cells (p < 0.001), and alleviated cell cycle arrest (p < 0.001). HFMSC-CNVs upregulated the expression of Collagen I (Col I), SMAD2/3, transforming growth factor beta (TGF-β), catalase (CAT), glutathione peroxidase-1 (GPX-1), and superoxide dismutase-1 (SOD-1) (p < 0.05) and downregulated the expression of cycle suppressor protein (p53), cell cycle suppressor protein (p21), and matrix metalloproteinase 3 (MMP3) (p < 0.05). Conclusively, the anti-photoaging properties of HFMSC-CNVs were confirmed both invivo and invitro. HFMSC-CNVs exert anti-photoaging effects by alleviating cell cycle arrest, decreasing cellular senescence and macrophage infiltration, promoting cell proliferation and extracellular matrix (ECM) production, and reducing oxidative stress by increasing the activity of antioxidant enzymes.

The therapeutic effects of ADSCs on photoaging of skin induced by UVB irradiation.

Skin photoaging affects appearance and is associated with a variety of skin diseases, even skin cancer. Therefore, the prevention and treatment of skin photoaging is very important. However, there is a lack of effective evaluation methods, so it is an urgent problem to explore a comprehensive, non-invasive and in vivo evaluation method. Adipose-derived mesenchymal stem cells (ADSCs) are widely used to improve skin conditions as easier to obtain and positive effects. Recently, as the development of ultrasound technology, skin ultrasound has been widely used. Changes in skin layer and structure can be observed by high-frequency ultrasound (HFUS). In addition, Shear wave elastography (SWE) technology can be used to monitor the change of skin hardness. However, it is necessary to further explore the ultrasound parameters in interpreting histological changes. We simulate the progression and treatment process of human skin photoaging by using UVB-induced nude mice skin photoaging model and ADSCs injection. The analysis of the degree and therapeutic effect of skin photoaging was conducted by HFUS, SWE and to verify with histopathology. Our study aims to clarify the value of HFUS combined SWE techniques in evaluating the degree and therapeutic efficacy of skin photoaging, which provides theoretical basis for diagnosis and treatment evaluation systems.

Lysine‐Based Ionic Liquid Enables Peptides to Reverse Skin Photoaging: From Leaves to Roots

AbstractPeptides and proteins are pharmacologically active and highly safe; however, their local delivery remains a challenge in the field of drug delivery. Based on this, a novel lysine‐based ionic liquid via proton transfer between lysine and malic acid that can overcome the difficulties in the application of copper peptides is developed. Density functional theory, molecular docking simulations, and experimental validation demonstrate the chemical stability of this ionic liquid. Furthermore, by combining it with a vegetable oil system, a biocompatible lysine‐based ionic liquid microemulsion system is constructed, which perfectly combines the high viscosity of ionic liquids and low viscosity of microemulsions. Multi‐dimensional analysis shows that the system not only leads to a dramatic elevation in the local penetration of copper peptides, but also enables copper peptides to effectively suppress skin aging. In addition, transcriptome sequencing analysis reveals that the system primarily regulates p53, p16, and ECM‐related signaling pathways to combat photoaging in the skin. Overall, a noninvasive, efficient, and convenient anti‐aging system with enormous potential is developed for the clinical prevention and treatment of skin photoaging.

Exploring the mechanism of MP gel against skin photoaging based on network pharmacology, molecular docking, and experimental validation.

Long-term and high exposure to UV radiation can lead to the development of skin photoaging diseases. Therefore, there is an ongoing need for more natural and safe drugs to prevent or treat skin photoaging diseases. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database were used to collect the active compounds and corresponding targets of Cnidii Fructus, Arnebiae Radix, Angelicae Sinensis Radix, Poria, and Borneolum. The GeneCards database and the NCBI Gene database were used to collect the targets of skin photoaging diseases. The STRING database was used to construct a protein-protein interaction network formed by the intersecting targets of drugs and diseases. The Metascape database was applied for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the targets. Molecular docking between active compounds and targets was verified by Autodock. After that, the skin photoaging model of mice was established and treated with MP gel. The skin characterization on the back of mice was observed, and the ameliorative effect of MP gel on skin photoaging was evaluated by histological and epidermal thickness assays. The MDA content and SOD activity were measured. Caspase-3 expression in mouse skin tissues was detected by immunohistochemistry, quantitative real-time polymerase chain reaction assay, and Western blot. The results of network pharmacology experiments showed that the natural drugs have multi-component, multi-target therapeutic disease characteristics. The results of animal studies showed that MP gel improved the health of photoaged skin, promoted skin structural integrity, had antioxidant properties and significantly inhibited caspase-3 expression. The experimental validation of the results of the preliminary network pharmacology analysis was carried out in animal experiments, which confirmed part of the mechanism of action of MP gel in the prevention and treatment of skin photoaging.

Autophagy plays an essential role in ultraviolet radiation-driven skin photoaging.

Photoaging is characterized by a chronic inflammatory response to UV light. One of the most prominent features of cutaneous photoaging is wrinkling, which is due primarily to a loss of collagen fibers and deposits of abnormal degenerative elastotic material within the dermis (actinic elastosis). These changes are thought to be mediated by inflammation, with subsequent upregulation of extracellular matrix-degrading proteases and down-regulation of collagen synthesis. Autophagy is a vital homeostatic cellular process of either clearing surplus or damaged cell components notably lipids and proteins or recycling the content of the cells’ cytoplasm to promote cell survival and adaptive responses during starvation and other oxidative and/or genotoxic stress conditions. Autophagy may also become a means of supplying nutrients to maintain a high cellular proliferation rate when needed. It has been suggested that loss of autophagy leads to both photodamage and the initiation of photoaging in UV exposed skin. Moreover, UV radiation of sunlight is capable of regulating a number of autophagy-linked genes. This review will focus on the protective effect of autophagy in the skin cells damaged by UV radiation. We hope to draw attention to the significance of autophagy regulation in the prevention and treatment of skin photoaging.

Molecule which changed the view on skin treatment

Objective — to study the modern classification, mechanisms of action and clinical effects of vitamin A derivatives, to analyze retinoid for local treatment of various dermatoses with a universal mechanism of action at the epidermis and dermis levels.&#x0D; Materials and methods. A review of the literature and an analysis of the results of international clinical trials of drugs based on the natural retinoid of the first generation — tretinoin (retinoic acid) is presented. The works of dozens of authors since 1980s to the present day are analyzed. Most sources provide detailed information on the results of topical retinoids in acne therapy, which are the base of clinical guidelines. Long-term (6 months or more) studies of retinoic acid-based preparations carried out in recent decades have discovered the unique clinical effects of tretinoin in the treatment of skin photoaging, actinic keratosis, etc. They are achieved due to the effect of tretinoid on the nuclear receptors of keratinocytes and fibroblasts.&#x0D; Results and discussion. The molecular mechanisms of action of retinoic acid, realizing the cellular and tissue effects of the most studied retinoid, are systematized and grouped in a single review. It has been proven that a unique feature of tretinin is its ability to activate directly all subtypes of RARs- and, indirectly, RARs-nuclear receptors of skin cells. A new modern drug for external use is presented — AltrenoТМ lotion containing micronized 0.05 % tretinoin in combination with sodium hyaluronate, soluble collagen and glycerin. This combination exhibits the expected clinical efficacy in acne therapy and prevents side effects such as dryness, redness and exfoliation. AltrenoТМ is approved for use in children of 9 years of age and older.&#x0D; Conclusions. Tretinoin (retinoic acid) is a modern powerful retinoid with a universal mechanism of action, recommended for the treatment of acne.

Efficacy and safety of Resveratrol combined with Ablative Fractional CO2 laser system in the treatment of skin photoaging

AbstractObjectiveTo evaluate the efficacy and safety of resveratrol combined with ablative fractional CO2 laser system (AFL) treating skin photoaging.MethodsThirty‐two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period.ResultsAll subjects in TG achieved improvements of their photoaging signs compared to pre‐treatment both the laser side and the non‐laser side at 6 months (p &lt; 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p &lt; 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p &lt; 0.05). On the non‐laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p &lt; 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG.ConclusionThe resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL.

Mitochondria-Targeted Hydrogen Sulfide Delivery Molecules Protect Against UVA-Induced Photoaging in Human Dermal Fibroblasts, and in Mouse Skin In Vivo.

Aims: Oxidative stress and mitochondrial dysfunction play a role in the process of skin photoaging via activation of matrix metalloproteases (MMPs) and the subsequent degradation of collagen. The activation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor controlling antioxidant and cytoprotective defense systems, might offer a pharmacological approach to prevent skin photoaging. We therefore investigated a pharmacological approach to prevent skin photoaging, and also investigated a protective effect of the novel mitochondria-targeted hydrogen sulfide (H2S) delivery molecules AP39 and AP123, and nontargeted control molecules, on ultraviolet A light (UVA)-induced photoaging in normal human dermal fibroblasts (NHDFs) in vitro and the skin of BALB/c mice in vivo. Results: In NHDFs, AP39 and AP123 (50-200 nM) but not nontargeted controls suppressed UVA (8 J/cm2)-mediated cytotoxicity and induction of MMP-1 activity, preserved cellular bioenergetics, and increased the expression of collagen and nuclear levels of Nrf2. In in vivo experiments, topical application of AP39 or AP123 (0.3-1 μM/cm2; but not nontargeted control molecules) to mouse skin before UVA (60 J/cm2) irradiation prevented skin thickening, MMP induction, collagen loss of oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased Nrf2-dependent signaling, as well as increased manganese superoxide dismutase levels and levels of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α). Innovation and Conclusion: Targeting H2S delivery to mitochondria may represent a novel approach for the prevention and treatment of skin photoaging, as well as being useful tools for determining the role of mitochondrial H2S in skin disorders and aging. Antioxid. Redox Signal. 36, 1268-1288.

Eficacia y seguridad de la lipotransferencia en el tratamiento del fotoenvejecimiento cutáneo

IntroductionAging is an inevitable process that depends on genetic and environmental factors. Facial photoaging is an expression of the effect of ultraviolet radiation and can be prevented in many ways, among which fat transfer has become popular. ObjectiveTo evaluate the efficacy and safety of fat transfer in the treatment of skin photoaging. Patients and methodAn observational, analytical and longitudinal study was carried out in 43 patients with cutaneous photoaging at the Hospital Clínico Quirúrgico «Hermanos Ameijeiras», in the period between February 1st, 2019 and February 28th, 2020. Lipoblotting was performed by the Coleman method. The nano-fat type adipose tissue was processed and administered. The response to treatment was used from the clinical point of view (3 months after having performed the procedure) using the Glogau Photo Damage Classification Scale, the Global Esthetic Improvement Scale and the Evaluative Scale of the severity range of the nasolabial fold (WSRS), with photographic evidence and with a surface microscope. ResultsAfter treatment, there were significant changes in the Glogau photodamage classification scale (P = 0.0002), in the Global Esthetic Improvement Scale (P = 0.019) and in the Evaluative Scale of the range of severity of the nasolabial fold (P = 0.0231). The adverse events found were pain, inflammation and ecchymosis; of mild or moderate intensity, without permanent consequences in individuals. The degree of satisfaction reported by the patients was good (4.7%) and very good (95.3%) (P = 0.0011). ConclusionsStem cell assisted fat transfer is effective and safe in correcting the signs of facial photoaging, with a high degree of patient satisfaction.

The effectiveness and safety of Chinese herbal formulas on skin photoaging: A protocol for systematic review and meta-analysis.

Background:Skin photoaging (SP) is a complex and complicated process of skin characteristic changes caused by excessive sunlight. Wrinkles, looseness, coarseness, and increase or loss of pigment are the main clinical manifestations of the disease. The pathogenesis of SP mainly involving oxidative stress, inflammatory reaction, immune dysregulation and DNA damage, and so on. In recent years, traditional Chinese medicine, as an significant form of complementary and alternative medicine, has attracted the more and more attention within the field of health care and indicated a desirable effect on SP. Chinese herbal formula (CHF) is an essential part of traditional Chinese medicine interventions, and the number of clinical trails on SP treated by CHFs have shown a growing trend. Therefore, we developed this systematic review and meta-analysis protocol to assess the effectiveness and safety of CHFs in the therapy of SP, so as to provide reliable evidence-based evidence for clinical decision-making.Methods:A overall literature retrieval will be carried out in 9 electronic journal database. We will include randomized controlled trials (RCTs) on CHFs alone or combined with routine western medicine measures in the treatment of SP. The outcomes we focused on are consists of symptom score (skin relaxation, telangiectasia, pore coarseness, pigmentation, etc), total effective rate, and adverse reactions. Meta-analysis will be performed using Stata 13.0 software. Literature retrieval and screening, data extraction, risk of bias assessment of RCTs, evidence confidence rating by grading of recommendations assessment, development, and evaluation method and methodological quality assessment of systematic review by assessment of multiple systematic reviews-2 will be conducted independently by 2 reviewers, and disagreements will be resolved through discussion or judged by a third senior reviewer.Results:This systematic review and meta-analysis will pool the proof of RCTs on SP treated by CHFs alone or combined with conventional western medicine treatments. The findings of this study will be presented at relevant conferences and submitted to peer-reviewed journals for publication.Conclusion:We expect that the results of this systematic review will provide comprehensive and reliable evidence for clinicians and policy makers.Registration number:INPLASY 2020120005

Antiphotoaging Effect of 3,5-Dicaffeoyl-epi-quinic Acid against UVA-Induced Skin Damage by Protecting Human Dermal Fibroblasts In Vitro.

Cutaneous aging is divided into intrinsic and exogenous aging correspondingly contributing to the complex biological phenomenon in skin. Intrinsic aging is also termed chronological aging, which is the accumulation of inevitable changes over time and is largely genetically determined. Superimposed on this intrinsic process, exogenous aging is associated with environmental exposure, mainly to ultraviolet (UV) radiation and more commonly termed as photoaging. UV-induced skin aging induces increased expression of matrix metalloproteinases (MMPs) which in turn causes the collagen degradation. Therefore, MMP inhibitors of natural origin are regarded as a primary approach to prevent or treat photoaging. This study investigated the effects of 3,5-dicaffeoyl-epi-quinic acid (DEQA) on photoaging and elucidated its molecular mechanisms in UVA-irradiated human dermal fibroblasts (HDFs). The results show that treatment with DEQA decreases MMP-1 production and increases type I collagen production in UVA-damaged HDFs. In addition, treatment of UVA-irradiated HDFs with DEQA downregulates MMP-1, MMP-3 and MMP-9 expression via blocking MAPK-cascade-regulated AP-1 transcriptional activity in UVA-irradiated HDFs. Furthermore, DEQA relieves the UVA-mediated suppression of type I procollagen and collagen expression through stimulating TGF-β/Smad signaling, leading to activation of the Smad 2/3 and Smad 4 nuclear translocation. These results suggest that DEQA could be a potential cosmetic agent for prevention and treatment of skin photoaging.

Purified Vitexin Compound 1 Inhibits UVA-Induced Cellular Senescence in Human Dermal Fibroblasts by Binding Mitogen-Activated Protein Kinase 1

Purified vitexin compound 1 (VB1), a novel lignanoid isolated from the seeds of the Chinese herb Vitex negundo, has strong antioxidant abilities and broad antitumor activities. However, little is known about its anti-photoaging effect on the skin and the underlying mechanism. Here, we demonstrated that VB1 significantly attenuates ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs), as evidenced by senescence-associated β-gal staining, MTT assays, and western blot analysis of the expression of p16 and matrix metalloproteinase-1 (MMP-1). Furthermore, mass spectrometry revealed that VB1 could directly bind to Mitogen-Activated Protein Kinase 1 (MAPK1). Molecular docking and molecular dynamics simulation methods confirmed the mass spectroscopy results and predicted six possible binding amino acids of MAPK1 that most likely interacted with VB1. Subsequent immunoprecipitation analysis, including different MAPK1 mutants, revealed that VB1 directly interacted with the residues, glutamic acid 58 (E58) and arginine 65 (R65) of MAPK1, leading to the partial reversal of UVA-induced senescence in HEK293T cells. Finally, we demonstrated that the topical application of VB1 to the skin of mice significantly reduced photoaging phenotypes in vivo. Collectively, these data demonstrated that VB1 reduces UVA-induced senescence by targeting MAPK1 and alleviates skin photoaging in mice, suggesting that VB1 may be applicable for the prevention and treatment of skin photoaging.

GaAlAs laser pretreatment enhances the function of ADSCs in photoaging of the skin in rats

Objective To investigate the effect of adipose-derived stem cells (ADSCs) on photoaging skin after laser pretreatment with GaAlAs. Methods ADSCs were isolated from healthy wistar rats, ADSCs were isolated and cultured to establish an adipose-derived stem cell culture system. ADSCs were pretreated with GaAlAs laser at a wavelength of 650 nm 4 J/cm2. A rat model of photoaging aging was established. Different doses of ADSCs and low energy laser ADSCs were pretreated with ADSCs for the treatment of photoaging skin, and the morphological changes of epidermis and dermis were observed before and after treatment with low energy laser pretreatment. Results When the concentration of ADSCs was 103/100 μl, there was no significant difference in epidermal thickness and dermal thickness between ADSCs treated group and GaAlAs pretreatment group (P>0.05). The thickness of epidermis in the GaAlAs pretreatment group was significantly lower than that in the ADSCs group (P<0.05) at 104/100 μl. When the concentration of ADSCs was 5×104/100 μl, the epidermal thickness of the GaAlAs pretreatment group decreased significantly and the thickness of the dermis increased significantly, which was significantly different from that of the ADSCs group (P<0.05). Conclusions GaAlAs laser pretreatment can enhance ADSCs anti-skin photoaging ability. Key words: Lasers; Multipotent stem cells; Cellular senescence; GaAlAs; Adipose-derived stem cells

In vitro study of RRS® Silisorg CE Class III medical device composed of silanol: effect on human skin fibroblasts and its clinical use.

IntroductionSilanol (organic silicon) has been used for decades in the treatment of skin photoaging as it stabilizes and maintains skin structures through hydrogen bonding electrostatic interaction with extracellular matrix (ECM) proteins or glycosaminoglycans. Organic silicon-based products are often presented as silanol derivatives which are currently associated to other structural molecules such as orthohydroxybenzoate, carboxymethyl theophylline alginate, ascorbate, acetyltyrosine, sodium lactate or mannuronate. Consequently, organic silicon formulations may differ substantially between the medical devices available on the market, which may result in additional effect on the skin. Therefore, there is a real need for a better characterization of the products in terms of their action on human skin and in vitro skin model.Materials and methodsIn this in vitro study, the effect of RRS® Silisorg was analyzed. RRS® Silisorg is a dermal implant (CE Class III medical device) containing monomethylsilanol mannuronate associated to an antioxidant resveratrol. Skin fibroblast viability and capacity to induce the production of key ECM genes were evaluated in the presence of different concentrations of RRS® Silisorg. The key ECM genes selected were collagen type I, elastin and hyaluronan synthase type 2 (HAS2), which is the cellular enzyme responsible for high-molecular weight hyaluronic acid (HA) production. Viability was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and expression was quantified by quantitative polymerase chain reaction.ResultsRRS® Silisorg increased fibroblast gene expression of HAS2 in the first 24 hours, 25 times in the presence of 1 mg/mL of solution, followed by a collagen type I gene expression (4.7 times) and elastin expression (2.5 times) increase after 48 hours.ConclusionThese results demonstrate that the silanol-based medical device RRS® Silisorg sustains HA, collagen and elastin production in human skin fibroblasts in vitro.

Protective Effect of Octylmethoxycinnamate against UV-Induced Photoaging in Hairless Mouse via the Regulation of Matrix Metalloproteinases.

Ultraviolet (UV) irradiation damages skin and produces symptoms of photoaging, such as thickening, rough texture, wrinkles, and pigmentation. However, the cellular and molecular mechanisms underlying photoaging induced by chronic UV irradiation are not yet fully understood. Matrix metalloproteinases (MMPs) have been reported to be involved in the response to UV irradiation. In this study, we examined the effects of the sunscreen agent Octylmethoxycinnamate (OMC) on photoaging of the skin induced by chronic UV exposure in hairless albino Crl:SKH1-Hrhr (SKH-1) mice. We demonstrated that the expression of MMPs was elevated by UV irradiation, whereas the topical application of OMC inhibited the upregulation of MMPs. Furthermore, UV-induced wrinkle formation was decreased by OMC treatment. These results suggest that OMC is a potential agent for the prevention and treatment of skin photoaging.

Remodeling of dermal collagen in photoaged skin using low-dose 5-aminolevulinic acid photodynamic therapy occurs via the transforming growth factor-β pathway.

5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is known to be effective in the treatment of photoaged skin. However, the molecular mechanisms still remain elusive. Protoporphyrin IX (PpIX) fluorescence is primarily located in the epidermis while ALA-PDT affects the dermal collagen, presumably by an indirect mechanism. This study aimed to investigate the molecular communication in low-dose ALA-PDT occurring between epidermal keratinocytes and dermal fibroblasts. Western blotting and enzyme-linked immunosorbent assays were performed to evaluate collagen expression and transforming growth factor-β (TGF-β) signaling in human keratinocytes and dermal fibroblasts. The impact on fibroblast proliferation was assessed by morphology and proliferating cell nuclear antigen immunofluorescence. Skin biopsies from mice were used to analyze the histological changes in dermal collagen and PpIX distribution. When fibroblasts were cocultured with keratinocytes treated with low-dose ALA-PDT, collagen synthesis and fibroblast proliferation were enhanced. Low-dose ALA-PDT stimulated TGF-β1 expression in keratinocytes. Fibroblasts cocultured with low-dose ALA-PDT-treated keratinocytes also showed activation of the TGF-β pathway. In vivo, PpIX fluorescence was densely distributed in photoaged mouse epidermis while collagen in the mouse dermis underwent remodeling. This study suggests that low-dose ALA-PDT can stimulate keratinocytes to release TGF-β1, activating the TGF-β pathway in dermal fibroblasts to remodel collagen in the dermis.

Retinoic acid ameliorates photoaged skin through RAR‑mediated pathway in mice.

Retinoic acid (RA), the bioactive metabolite of vitamin A, has demonstrated efficacy in the treatment of photoaged skin; however, the mechanism of action of RA remains unclear. The aim of the present study was to examine whether the therapeutic effects of RA on photoaged skin are mediated by retinoic acid receptor (RAR) and/or retinoid X receptor (RXR) in mice, and to investigate the underlying mechanism. Photoaged skin in Imprinting Control Region mice was induced by repeated exposure to ultraviolet (UV) irradiation. Mice were randomly divided into nine groups: Normal; UV control; all‑trans retinoic acid (ATRA); ATRA+RAR antagonist; ATRA+RXR antagonist; RAR agonist; RAR agonist+RAR antagonist; RXR agonist; and RXR agonist+RXR antagonist. Masson's trichrome staining was used to examine skin collagen fibers. Hydroxyproline assays were used to determine collagen content. The protein expression of matrix metalloproteinase (MMP)‑3, MMP‑13, type I procollagen, c‑Jun and c‑Fos was detected using western blot analysis. The results demonstrated that ATRA and RAR agonist ameliorated the UV‑induced damage to skin collagen fibers, and increased the collagen content in photoaged skin through RAR. Furthermore, ATRA and RAR agonist stimulated type I procollagen protein expression, and inhibited MMP‑3, MMP‑13 and c‑Jun protein expression through RAR in photoaged skin. However, ATRA and RAR agonist exhibited no significant effect on the protein expression of c‑Fos in photoaged skin. These findings suggest that RA ameliorates photoaged skin through a RAR‑mediated signaling pathway in mice.

Histological and Immunohistochemical Evaluation of the Efficacy of a New Cosmetic Formulation in the Treatment of Skin Photoaging

Objective. Mechanism of action of cosmetic products is not often studied. The aim of this study is to determine the histological, immunohistochemical, and clinical changes of a new cosmetic formulation. Methods. Prospective, single-blind, patient-controlled, randomized study in 10 volunteers with mild to moderate skin photoaging on the back of their hands. The product was applied on one hand and a standard cream on the other hand, twice a day for three months. Standardized photographs were taken on basal (T0) and final visit (T1) and skin biopsies were performed. Changes on histological and immunohistochemical markers were studied. Subjective clinical changes were determined. Results. After treatment, a 26.3% improvement on epidermal thickness was detected and a significant increase on collagens I and III, elastin, and fibronectin fibers was achieved (p < 0.05). As the expression of MMPs remained stable, this improvement of dermal matrix was attributed to the stimulation of their synthesis. A significant clinical improvement on the treated hand was obtained, compared to control hand. Conclusion. This new cosmetic product with combination of three registered technologies (IFC-CAF, WGC, and RetinSphere), focused on regenerating dermal matrix and activating proliferation of skin cells, has shown to be efficient in the reversion of skin photoaging.