Procollagen Synthesis Research Articles

Prospects for Treatment of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severe, progressive lung disease of unknown etiology with an average worldwide prevalence of 15 per 100,000. According to the etiology, IPF is classified into sporadic, syndromic, and familial cases. Sporadic cases refer to multifactorial diseases and are associated with age, viral infections, smoking and inhalation of dust, contact with chemicals and drugs, gastroesophageal reflux disease. There were revealed an association of sporadic IPF with allelic variants of the genes AKAP13, ATP11A, DPP9, DSP, IVD, IL1RN, FAM13A, MUC5B, SFTPC, SPPL2C, TERC, TERT, TOLLIP. Syndromal IPF develops in German-Pudlak syndrome. Familial cases of the disease are caused by mutations in the genes encoding surfactant (SFTPC), mucin (MUC5B), deadenylation nuclease (PARN), components of telomere functioning (RTEL1, TERC, TERT). In 2000, the American Thoracic Society recommended glucocorticoids and cytostatics for the treatment of ELISA in order to influence the inflammatory process due to the activation of fibroblasts and their accumulation in the extracellular matrix of the lungs. These recommendations are still used by many doctors, despite the publication of reliable data on the increased mortality and hospitalizations of IPF patients taking prednisolone and azathioprine. According to recent meta-analyzes, pirfenidone (an inhibitor of the synthesis of procollagen I and II growth factors) and nintenadib (a tyrosine kinase inhibitor) are the most effective treatments for IPF. Since genetic factors play an important role in the etiopathogenesis of the disease, it is promising to search for methods of targeted therapy for IPF using specific noncoding RNAs as targets, changes in the expression of which are not specific of other bronchopulmonary diseases. These RNAs include miR-9-5p, miR-27b, miR-153, miR-184, miR-326, miR-374, miR-489, miR-630, miR-1343 (decreased expression in IPF); miR-340, miR-424, miR-487b, miR-493, lncRNA AP003419.16, lncRNA AP003419.16 (increased expression in IPF).

Effect of Vitamin C on Tendinopathy Recovery: A Scoping Review.

Tendinopathies represent 30–50% of all sports injuries. The tendon response is influenced by the load (volume, intensity, and frequency) that the tendon support, resulting in irritability and pain, among others. The main molecular component of tendons is collagen I (60–85%). The rest consist of glycosaminoglycans-proteoglycans, glycoproteins, and other collagen subtypes. This study’s aim was to critically evaluate the efficacy of vitamin C supplementation in the treatment of tendinopathies. At the same time, the study aims to determine the optimal conditions (dose and time) for vitamin C supplementation. A structured search was carried out in the SCOPUS, Medline (PubMed), and Web of Science (WOS) databases. The inclusion criteria took into account studies describing optimal tendon recovery when using vitamin C alone or in combination with other compounds. The study design was considered, including randomized, double-blind controlled, and parallel designs in animal models or humans. The main outcome is that vitamin C supplementation is potentially useful as a therapeutic approach for tendinopathy recovery. Vitamin C supplementation, alone or in combination with other products, increases collagen synthesis with a consequent improvement in the patient’s condition. On the other hand, vitamin C deficiency is mainly associated with a decrease in procollagen synthesis and reduced hydroxylation of proline and lysine residues, hindering the tendon repair process.

Photobiomodulation assay of muscle cells C2C12 after irradiation with LED device

Introduction: One of the ways that have been observed to reduce musculoskeletal fatigue is the use of protocols for the application of light sources (photobiomodulation) such as low-intensity laser and LED (Light Emitting Diode). Work involving photobiomodulation has shown promising results in strength performance or reduction of muscle fatigue. At the cellular level, photobiomodulation can modulate fibroblasts proliferation, the fixation and synthesis of collagen and procollagen, promote angiogenesis and improving energy metabolism in mitochondria. Compared with laser devices, LED has several advantages, such as being smaller, lighter, lower cost, and easier for operation. Objective: The present work objective is to verify if irradiation with LED device (650 nm and 860 nm) in muscle cells C2C12 modify the viability, morphology and cytoskeleton components. Methodology: C2C12 cells line (ATCC CRL - 1772) were cultured in 25 cm2 bottles at 37ºC under 5% CO2 in DMEM. The cells were irradiated with the light-emitting diodes (LED) device, Sportllux Ultra that consists of 84 LEDs, each individual LED has 8 mW of power, emitting in 660±20 nm (42 LEDs) and 850±20 nm (42 LEDs), and covering an area (A) of 120 cm2. The power density of delivered light was 5,6 mW/cm2, and the exposure time was 10 minutes, totalizing the fluence of 3,4 J/cm2. Viability assay was performed where the cells were incubated with 100 µL of Crystal Violet (CV) solution and mitochondrial activity assay was evaluated by the colorimetric MTT assay. Nucleus (DAPI) and Cytoskeleton (Rhodamine Phalloidin) fluorescence assay was performed to study the cytoskeleton based on the change in the actin filaments. Results: Our results demonstrate that the synergism of LED irradiation (660nm and 850nm) induced the proliferation of C2C12 cells. The light-emitting diode (LED) device, Sportllux Ultra has a significant effect on C2C12 cell culture. Mitochondrial activity and cell viability showed a significative increase in their activities after irradiation. The microscopy fluorescence observations showed an alignment of cytoskeletal components of C2C12 cells after irradiation. Conclusion: The application of irradiation with the Sportlux Ultra LED device stimulated an increase of energy by mitochondrial activity assay, number of cells by cell viability assay and alignment of cytoskeleton components by fluorescence assay in C2C12 line cells. Our results suggest that organizated cytoskeletal actin filaments normally contribute to cell survival and that induced major cell changes in the cytoskeleton that result in cell shape change. These results suggest that the Sport Lux Ultra LED device can help in the repair of tissue injuries and to collaborate to increase of performance in athletes in a faster way.

Anti-Photoaging Effect of Hydrolysates from Pacific Whiting Skin via MAPK/AP-1, NF-κB, TGF-β/Smad, and Nrf-2/HO-1 Signaling Pathway in UVB-Induced Human Dermal Fibroblasts.

Chronic exposure to ultraviolet (UV) light promotes the breakdown of collagen in the skin and disrupts the extracellular matrix (ECM) structure, leading to skin wrinkling. Pacific whiting (Merluccius productus) is a fish abundant on the Pacific coast. In the current study, we investigated the anti-wrinkle effect of hydrolysate from Pacific whiting skin gelatin (PWG) in UVB-irradiated human dermal fibroblasts and the molecular mechanisms involved. PWG effectively restored type 1 procollagen synthesis reduced by UVB-irradiation. Also, we found that PWG inhibited collagen degradation by inhibiting MMP1 expression. Furthermore, PWG decreased cytokines TNF-α, IL-6, and IL-1β associated with inflammatory responses and increased antioxidant enzymes, HO-1, SOD, GPx, CAT, and GSH content, a defense system against oxidative stress. In terms of molecular mechanisms, PWG increased collagen synthesis through activating the transforming growth factor β (TGF-β)/Smad pathway and decreased collagen degradation through inhibiting the mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1) pathway. It also suppressed the inflammatory response through suppressing the nuclear factor-κB (NF-κB) pathway and increased antioxidant enzyme activity through activating the nuclear factor erythroid 2/heme oxygenase 1 (Nrf-2/HO-1) pathway. These multi-target mechanisms suggest that PWG may serve as an effective anti-photoaging material.

Visualized procollagen Iα1 demonstrates the intracellular processing of propeptides.

The processing of type I procollagen is essential for fibril formation; however, the steps involved remain controversial. We constructed a live cell imaging system by inserting fluorescent proteins into type I pre-procollagen α1. Based on live imaging and immunostaining, the C-propeptide is intracellularly cleaved at the perinuclear region, including the endoplasmic reticulum, and subsequently accumulates at the upside of the cell. The N-propeptide is also intracellularly cleaved, but is transported with the repeating structure domain of collagen into the extracellular region. This system makes it possible to detect relative increases and decreases in collagen secretion in a high-throughput manner by assaying fluorescence in the culture medium, and revealed that the rate-limiting step for collagen secretion occurs after the synthesis of procollagen. In the present study, we identified a defect in procollagen processing in activated hepatic stellate cells, which secrete aberrant collagen fibrils. The results obtained demonstrated the intracellular processing of type I procollagen, and revealed a link between dysfunctional processing and diseases such as hepatic fibrosis.

Anemopsis californica Attenuates Photoaging by Regulating MAPK, NRF2, and NFATc1 Signaling Pathways.

Long-term exposure of the skin to solar radiation causes chronic inflammation and oxidative stress, which accelerates collagen degradation. This contributes to the formation of wrinkles and dark spots, skin fragility, and even skin cancer. In this study, Anemopsis californica (AC), a herb from North America that is well known for treating microorganism infection and promoting wound healing, was investigated for its photoprotective effects. The biological effects of AC were studied on two in vitro models, namely, lipopolysaccharide (LPS)-induced macrophages and ultraviolet B (UVB)-irradiated dermal fibroblasts, to characterize its underlying molecular mechanisms. The results showed that AC decreased the mRNA levels of inflammatory mediators in sensitized macrophages, including cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Moreover, AC alleviated UVB-induced photoaging in dermal fibroblasts by restoring procollagen synthesis. This resulted from the regulation of excessive reactive oxygen species (ROS) by AC, which was mediated by the activation of the antioxidative system nuclear factor erythroid 2-related factor 2 (NRF2). AC also alleviated oxidative stress and inflammatory responses by inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK) and interfering with the nuclear translocation of the immune regulator nuclear factor of activated T-cells 1 (NFATc1). In conclusion, the protective effects of AC on skin cellular components suggested that it has the potential for use in the development of drugs and cosmetics that protect the skin from UVB-induced chronic inflammation and aging.

English

Abeliophyllum distichum Nakai is a deciduous shrub that belongs to Oleaceae Abeliophyllum and grows only in Korea. In this study, the antioxidative activity, cytotoxicity, anti-aging activity, and levels of acteoside and isoacteoside were compared between non-fermented and fermented (using Lactobacillus plantarum and Lactobacillus brevis) extracts of A. distichum Nakai. The cytotoxicity of these extracts, along with their ability to inhibit elastase activity and Matrix metalloproteinase-1 (MMP-1) expression, and their ability to promote type I procollagen synthesis were investigated in human dermal fibroblasts cells. These tests revealed that the fermented extract possessed higher antioxidant and anti-aging activities compared with the non-fermented extract. The levels of acteoside and isoacteoside were about 1.25 and 1.05 times higher in the fermented extract than in the non-fermented extract. It was speculated that they were converted from acteoside glucosides and isoacteoside glucosides via bioconversion by the fermentation strains. Together, these findings indicate that extracts of A. distichum Nakai show good potential as antioxidative and anti-aging cosmetic materials.   Key words: Abeliophyllum distichum Nakai, Lactobacillus plantarum, Lactobacillus brevis, fermentation, antioxidative activity, anti-aging activity.

Artificial Neural Network Modeling of Nanostructured Lipid Carriers Containing 5-O-Caffeoylquinic Acid-Rich Cratoxylum formosum Leaf Extract for Skin Application.

Purpose: To investigate the in vitro anti-skin-aging properties of Cratoxylum formosum extract and encapsulate this plant extract in nanostructured lipid carriers (CFE-NLCs) for dermal application. Methods: The biological properties of the plant extract, including enhanced procollagen type I synthesis and anti-matrix metalloproteinase activity, were evaluated to assess its cosmetic benefits. An artificial neural network (ANN) coupled with K-fold cross-validation was applied to investigate the effects of the formulants and optimize the CFE-NLCs. The physicochemical properties, percutaneous absorption, and irritation potential of the CFE-NLCs were analyzed. Results: Liquid chromatography-mass spectrometry analysis revealed that CFE contained 5-O-caffeoylquinic acid as the vital constituent. Appropriate skin-care properties were also demonstrated with respect to enhanced type I procollagen synthesis and the inhibition of MMP-1, MMP-3, and MMP-9 in primary human dermal fibroblasts. The optimal CFE-NLCs exhibited better skin absorption and biocompatibility and lower irritation potential than the free botanical extract solution. Conclusion: The findings obtained highlight CFE-NLCs as promising skin-care ingredients.

Antiphotoaging properties of Zingiber montanum essential oil isolated by solvent-free microwave extraction against ultraviolet B-irradiated human dermal fibroblasts.

Maintaining youthful skin from photoaging with natural products, including essential oils, is a vital strategy that has piqued the interest of researchers in the pharmaceutical and cosmetic industries. This research aimed to investigate the protective properties of Zingiber montanum (J. Koenig) Link ex A. Dietr. essential oil against ultraviolet B (UVB)-induced skin damage and photoaging in normal human dermal fibroblast (HDFn) cells. The essential oil was extracted from fresh plant rhizomes using solvent-free microwave extraction. Its antiphotoaging properties in HDFn cells were investigated using reactive oxygen species (ROS)-scavenging, wound healing, matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) expression, procollagen synthesis, and elastase and tyrosinase inhibitory assays. The results showed that the test oil exhibited no significant toxicity in HDFn at concentrations up to 10mg/mL, with cell viability exceeding 90%. Following UVB irradiation at 30mJ/cm2, Z. montanum oil demonstrated time and concentration-dependent ROS radical scavenging capabilities. In a cell migration assay, the essential oil demonstrated wound-healing properties. Z. montanum oil suppressed the expression of MMPs and enhanced the synthesis of type I procollagen at a concentration of 0.1-1mg/mL. In addition, 0.1-1mg/mL Z. montanum oil inhibited elastase activity in a concentration-dependent manner but did not affect tyrosinase activity. From these findings, the essential oil of Z. montanum could have potential applications in developing cosmeceutical products to prevent skin photoaging.

잣나무 잎 추출물의 생리활성 및 주름개선 효능

Background: This study assessed the role of Pinus koraiensis (P. koraiensis) Siebold et Zucc. leaves as an ingredient for cosmetics. The biological activities and wrinkle improvement effect of P. koraiensis leaves were investigated.<BR>Methods and Results: Leaf samples were mixed with 80% ethanol (EtOH), and the ingredients were separated into fractions using different solvents in order of n-Hexane, ethyl acetate (EtOAc), n-butanol and water. The antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH), scavenging of 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and total phenol and flavonoid content of 80% EtOH extracts and fractions was tested. Among the tested extracts and fractions, the EtOAc fraction displayed the greatest DPPH and ABTS scavenging activity and total phenol and flavonoid content. Wrinkle improvement was evaluated by performing collagenase and elastase assays. In addition, matrix metallopeptidase 1 (MMP-1) inhibition and procollagen synthesis were measured. The 80% EtOH extract displayed the greatest anti-wrinkle effects.<BR>Conclusions: The 80% EtOH extract and each fraction of P. koraiensis leaves displayed differing antioxidant and anti-wrinkle activities. This basic data will inform the utilization these P. koraiensis as an ingredient suitable for skin health and beauty.

NaHS-Hydrogel and Encapsulated Adipose-Derived Stem Cell Evaluation on an Ex Vivo Second-Degree Burn Model

Second-degree burns result in the loss of the epidermal barrier and could lead to delayed complications during the healing process. Currently, therapeutic options to treat severe burns are limited. Thus, this work aims to evaluate the effect of NaHS, a hydrogen sulfide (H2S) donor, in poloxamer hydrogel in topical application and the potentiating effect of injected encapsulated adipose-derived stem cells (ASCs) compared to monolayer ASCs using our previous second-degree burn model on human skin explants. Indeed, our model allows testing treatments in conditions similar to a clinical application. The observed benefits of NaHS may include an antioxidant role, which might be beneficial in the case of burns. Concerning ASCs, their interest in wound healing is more than well documented. In order to evaluate the efficiency of our treatments, we analyzed the kinetics of wound closure, keratinocyte proliferation, and dermal remodeling. The effect of NaHS led to a delay in re-epithelialization, with a decrease in the number of proliferating cells and a decrease in the synthesis of procollagen III. On the contrary, intradermal injection of ASCs, encapsulated or not, improves wound healing by accelerating re-epithelialization and collagen I synthesis; however, only encapsulated ASCs accelerate keratinocyte migration and increase the rate of procollagen III and collagen III. In conclusion, NaHS treatment did not improve burn healing. However, the injection of ASCs stimulated wound healing, which is encouraging for their therapeutical use in burn treatment.

Pheophorbide a Derivatives Exert Antiwrinkle Effects on UVB-Induced Skin Aging in Human Fibroblasts.

Pheophorbide a is a chlorophyll metabolic breakdown product. This study investigated the antiwrinkle effect of pheophorbide a (PA) and its derivatives, including pyropheophorbide a (PyroPA) and pyropheophorbide a methyl ester (PyroPA-ME), on ultraviolet (UV) B-stimulated CCD-986sk fibroblasts. PA, PyroPA, and PyroPA-ME effectively suppressed reactive oxygen species accumulation in UVB-exposed CCD-986sk fibroblasts. All three pheophorbides also reduced UVB-induced matrix metalloproteinase (MMP)-1 secretion and mRNA expression of MMP-1, MMP-2, and MMP-9. Treatment with pheophorbides resulted in increased procollagen synthesis, and this required enhancement of procollagen type I C-peptide content and mRNA expression of collagen type I alpha 1 (COL1A1) and COL1A2 in CCD-986sk cells. These antiwrinkle effects were more potent with PA and PyroPA than with PyroPA-ME. Furthermore, PA and PyroPA suppressed UVB-induced phosphorylation of extracellular signal-regulated protein kinase and c-Jun N-terminal kinase but not p38. Moreover, all three pheophorbides inhibited NF-κB p65 phosphorylation. Therefore, these pheophorbides, especially PA and PyroPA, can be used as antiwrinkle agents, and PA- or PyroPA-rich natural resources can be used in functional cosmetics.

Fermentation of Panax notoginseng root extract polysaccharides attenuates oxidative stress and promotes type I procollagen synthesis in human dermal fibroblast cells

BackgroundPanax notoginseng is one of the most valuable traditional Chinese medicines. Polysaccharides in P. notoginseng has been shown to significantly reduce the incidence of human diseases. However the application of fermentation technology in Panax notoginseng is not common, and the mechanism of action of P. notoginseng polysaccharides produced by fermentation is still unclear. The specific biological mechanisms of fermented P. notoginseng polysaccharides (FPNP) suppresses H2O2-induced apoptosis in human dermal fibroblast (HDF) and the underlying mechanism are not well understood.MethodsIn this study, the effects of water extracted and fermentation on concentration of polysaccharides in P. notoginseng extracts were analyzed. After the H2O2-induced HDF model of oxidative damage was established, and then discussed by the expression of cell markers, including ROS, MDA, SOD, CAT, GSH-Px and MMP-1, COL-I, ELN, which were detected by related ELISA kits. The expression of TGF-β/Smad pathway markers were tested by qRT-PCR to determine whether FPNP exerted antioxidant activity through TGF-β signaling in HDF cells.ResultsThe polysaccharide content of Panax notoginseng increased after Saccharomyces cerevisiae CGMCC 17452 fermentation. In the FPNP treatment group, ROS and MDA contents were decreased, reversed the down-regulation of the antioxidant activity and expression of antioxidant enzyme (CAT, GSH-Px and SOD) induced by H2O2. Furthermore, the up-regulation in expression of TGF-β, Smad2/3 and the down-regulation in the expression of Smad7 in FPNP treated groups revealed that FPNP can inhibit H2O2-induced collagen and elastin injury by activating TGF-β/Smad signaling pathway.ConclusionIt was shown that FPNP could inhibit the damage of collagen and elastin induced by H2O2 by activating the TGF-β/Smad signaling pathway, thereby protecting against the oxidative damage induced by hydrogen peroxide. FPNP may be an effective attenuating healing agent that protects the skin from oxidative stress and wrinkles.

Extracts of red seaweed, Pyropia yezoensis, inhibit melanogenesis but stimulate collagen synthesis

Owing to increasing concern regarding human well-being and quality of life, the demand for natural products is increased, leading to the development of a market for biological and natural products. This study aimed to investigate the depigmentation and anti-ageing properties of red seaweed (Pyropia yezoensis) extracts for skin care applications. Within the tested range of concentrations (100, 200, 400, and 800 μg mL−1), P. yezoensis extracts did not exert cytotoxic effects on the three skin cell lines tested: mouse melanocytes (Melan-A), human dermal fibroblasts (1064 SK), and human dermal keratinocytes (HaCaT cells). No significant statistical difference (p = 0.05) was detected in the melanin content between cells exposed to 100 μg mL−1 of arbutin and 800 μg mL−1 of P. yezoensis extracts, indicating that P. yezoensis extracts had an potent inhibitory effect on melanogenesis as arbutin. There was a significant decrease in tyrosinase activity by 59.3% and 35.5% after treatment with arbutin and P. yezoensis extracts, respectively. These results indicated that P. yezoensis extracts had strong tyrosinase inhibitory properties but were not as effective as arbutin. P. yezoensis extracts also promoted collagen production by inhibiting collagen-degrading enzymes (matrix metalloproteinase (MMP)-2 and MMP-9) and promoting procollagen synthesis enzymes (tyrosinase-related protein (TRP)-1 and TRP-2). Evaluation of skin brightness and melanin content and dermatological assessment showed that P. yezoensis extracts enhanced skin brightness and reduced melanin content in 23 volunteers. Our results suggest that P. yezoensis extracts can be used as functional cosmetic agents to prevent, or remediate skin ageing and pigmentation.

Wound Healing Properties of Pomegranate

Pomegranate is rich in bioactive compounds such as anthocyanidins, proanthocyanidins, hydrolysable and non-hydrolysable tannins, flavanones, isoflavones, flavanols, flavones, phenolic acids and hydroxy-benzoic acids, with antioxidant, anti-microbial, anti-inflammatory, anti-biofilm, anti-quorum sensing and immunomodulatory properties. Wound healing is a complex process and at the same time in the wound aria is possible to exist microbes, biofilm, reactive oxygen radicals, and to occur quorum sensing, oxidative stress, inflammation, infection, while tissue repair functions are also taking place. Pomegranate through its’ various bioactivities is getting involved in various biochemical paths and functions during wound healing process and contribute thus by all these ways into healing process. Pomegranate juice, plant parts extracts and phytochemicals treatment accelerate wound healing process, increases wound contraction, reduces healing period, manages pain, enhances DNA, protein, hydroxyproline and collagen production, stimulates synthesis of type-1 procollagen and fibroblasts production and migration, leads to excellent epithelialization, neovascularization and granulation tissue organization. In diabetic patients, pomegranate treatment upregulates the levels of VEGF, EGF and TGF-β1 enhancing wound healing. Moreover, pomegranate reduces microbes count that may lead to infection, inhibits biofilm formation and attenuates preformed biofilms, inhibits quorum sensing and swimming motility that contribute to biofilm formation downregulating the expression of specific bacteria related to swimming motility and quorum sensing. As a strong antioxidant, immunomodulatory and anti-inflammatory agent, pomegranate inhibits oxidative stress, downregulates NOS activity and NO production, inhibits the endothelial activation of genes which predispose to oxidation sensitivity, increases the levels of the antioxidant enzymes glutathione, glutathione peroxidase and catalase, reduces immune cells’ count and stimulates keratinocytes proliferation that play a key role in immune defense against infection. Is important to be mentioned that pomegranate treated effectively acute and chronic wounds such as surgical, incision, excision, burn, oral lichen planus, gingival, aphthous stomatitis, diabetic wounds and gastric ulcers giving results better or comparable to commercial medicines without any adverse effects, while antibiotics and corticosteroids cause side effects that may be severe. These results indicate that pomegranate could possibly be considered as an alternative, safe, multifunctional, wound healing agent.

The Skin Interactome: A Holistic "Genome-Microbiome-Exposome" Approach to Understand and Modulate Skin Health and Aging.

Higher demands on skin care cosmetic products for strong performance drive intense research to understand the mechanisms of skin aging and design strategies to improve overall skin health. Today we know that our needs and influencers of skin health and skin aging change throughout our life journey due to both extrinsic factors, such as environmental factors and lifestyle factors, as well as our intrinsic factors. Furthermore, we need to consider our microflora, a collection of micro-organisms such as bacteria, viruses, and fungi, which is a living ecosystem in our gut and on our skin, that can have a major impact on our health. Here, we are viewing a holistic approach to understand the collective effect of the key influencers of skin health and skin aging both reviewing how each of them impact the skin, but more importantly to identify molecular conjunction pathways of these different factors in order to get a better understanding of the integrated “genome-microbiome-exposome” effect. For this purpose and in order to translate molecularly the impact of the key influencers of skin health and skin aging, we built a digital model based on system biology using different bioinformatics tools. This model is considering both the positive and negative impact of our genome (genes, age/gender), exposome: external (sun, pollution, climate) and lifestyle factors (sleep, stress, exercise, nutrition, skin care routine), as well as the role of our skin microbiome, and allowed us in a first application to evaluate the effect of the genome in the synthesis of collagen in the skin and the determination of a suitable target for boosting pro-collagen synthesis. In conclusion, we have, through our digital holistic approach, defined the skin interactome concept, as an advanced tool to better understand the molecular genesis of skin aging and further develop a strategy to balance the influence of the exposome and microbiome to protect, prevent, and delay the appearance of skin aging signs and preserve good skin health condition. In addition, this model will aid in identifying and optimizing skin treatment options based on external triggers, as well as helping to design optimal treatments modulating the intrinsic pathways.

Microbial Production of Retinyl Palmitate and Its Application as a Cosmeceutical

Chemically synthesized retinyl palmitate has been widely used in the cosmetic and biotechnology industry. In this study, we aimed to demonstrate the microbial production of retinyl palmitate and the benefits of microbial retinyl palmitate in skin physiology. A heterologous retinyl palmitate biosynthesis pathway was reconstructed in metabolically engineered Escherichia coli using synthetic expression modules from Pantoea agglomerans, Salinibacter ruber, and Homo sapiens. High production of retinyl palmitate (69.96 ± 2.64 mg/L) was obtained using a fed-batch fermentation process. Moreover, application of purified microbial retinyl palmitate to human foreskin HS68 fibroblasts led to increased cellular retinoic acid-binding protein 2 (CRABP2) mRNA level [1.7-fold (p = 0.001) at 100 μg/mL], acceleration of cell proliferation, and enhancement of procollagen synthesis [111% (p < 0.05) at 100 μg/mL], strongly indicating an anti-ageing-related effect of this substance. These results would pave the way for large-scale production of retinyl palmitate in microbial systems and represent the first evidence for the application of microbial retinyl palmitate as a cosmeceutical.

In cardiac fibroblasts, interferon-beta attenuates differentiation, collagen synthesis, and TGF-β1-induced collagen gel contraction

Cardiac fibroblasts (CF) play a key role in the homeostasis of the extracellular matrix in cardiac tissue and are newly recognized as inflammatory supporter cells. Besides, CF-to-Cardiac myofibroblast differentiation is commanded by TGF-b, through SMAD signaling pathways, and these last cells are strongly implicated in cardiac fibrosis. In the heart IFN-β is produced by CF; however, the role of IFN-β, STAT proteins, and STAT-homo or heterodimers in the regulation of CF function with or without a fibrotic environment is unknown. CF were isolated from hearts of adult rats, and by western blot analysis we studied STAT1, STAT2, and STAT3 phosphorylation and through specific siRNA against these proteins we analyzed their role in CF functions such as differentiation (α-SMA expression); and pro-collagen type-I synthesis and secretion expression levels; collagen gels contraction and CF migration. In cultured adult rats CF, IFN-β increases phosphorylation of STAT1, STAT2, and STAT3. Both STAT1 and STAT2 were involved in decreasing α-SMA and CF migration induced by TGF-β1. Also, IFN-β through STAT1 regulated pro-collagen type-I protein expression levels, and collagen gels contraction induced by TGF-β1. STAT3 was not involved in any effects of IFN-β studied.In conclusion, IFN-β through STAT1 and STAT2 shows antifibrotic effects on CF TGF-β1-treated, whereas STAT3 did not participate in such effect.

Comparison of antiaging, anti-melanogenesis effects, and active components of Raspberry (Rubus occidentalis L.) extracts according to maturity.

In this study, we carried out a comparative evaluation of antiaging and anti-melanogenesis activities of raspberry extracts (Rubus occidentalis L.) according to their stage of ripening (uRo: unripe raspberry, Ro: ripe raspberry), and analyzed the active component (ellagic acid) present in these extracts. Our results showed higher inhibitory effects of the uRo extract in terms of elastase and collagenase activities than Ro extract. In the CCD-986sk cells, uRo extract significantly inhibited MMP-1 activity by 18% and increased the rate of type 1 pro-collagen synthesis by 25%. Besides, treatment with uRo extract significantly inhibited α-melanocyte-stimulating hormone-induced melanin synthesis and tyrosinase activity in B16F10 mouse melanoma cells. Overall, uRo was a more potent mediator of antiaging and anti-melanogenesis effects than Ro extract. Further analysis showed that the functional effects of uRo could be attributed to its 18.5 times higher ellagic acid content than that in Ro extract. PRACTICAL APPLICATIONS: This study reported the differential effect of the raspberry extracts depending on their stage of ripening. To the best of our knowledge, this was the first study to report the antiaging, anti-wrinkle, and anti-pigmentation effects of the uRo extracts. We showed that the extracts from the uRo have an overall better antiaging and skin-whitening effect than ripe ones. The effects were attributed to high ellagic acid content in uRo. We believed that our study makes a significant contribution to the literature because the outcome of the study has both, cosmetic as well as therapeutic implications.

Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants.

Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the unique properties of the human skin. Based on previously described models of burn injury performed on human skin explants, we hypothesized that maintaining explants under constant tension forces would allow to more closely reproduce the pathophysiological processes of skin remodeling. We thus. Here, we set up and characterized an improved model of deep second-degree burn injury on ex vivo cultured human skin explants at air-liquid interface and maintained under conditions of constant tension forces. A spontaneous re-epithelialization of the lesion was observed 8 to 9 days post burn and was found to rely on the proliferation of basal keratinocytes at the wound edges. Collagen VII at the dermo-epidermal junction reformed along with the progression of re-epithelializatio and a synthesis of procollagen III was observed in the dermis at the wound site. These findings indicate that our model is suitable for the assessment of clinically-relevant therapies aimed at modulating the kinetics of re-epithelialization and/or the activation of fibroblasts following skin burn injuries. In this regard, we evaluated the use of a thermoreversible poloxamer hydrogel as a vehicle for topically-testable therapeutic molecules. Our data showed that, although useful for drug formulation, the p407/p188 poloxamer hydrogel induces a delay of skin re-epithelialization in humans skin explants submitted to experimental burn injury.