OBJECTIVE:Collagens are widely studied proteins given their implications in the skin extracellular matrix and pathological conditions such as fibrosis. Type V collagen is a member of the fibrillar collagens, and three different polypeptide chains, α1, α2 and α3 form isoforms through associations. The third chain, α3, of type V collagen was initially identified in the placenta, but after decades, it remains poorly characterized. The aim of this study is to investigate the expression and localization of the α3 chain of type V collagen in the skin and its evolution during skin aging. The identification of α3(V) collagen as a target of retinoic acid and its interaction with matrix metalloproteinase-9 (MMP-9) was investigated. METHODS:The expression and localization of α3(V) collagen were assessed by immunodetection in ex vivo skin and in keratinocytes using a calcium-differentiated model. The variation in α3(V) collagen expression during aging was studied in ex vivo skin from donors of different ages. The modulation of α3(V) collagen by retinoic acid was investigated by qPCR in keratinocytes and by immunofluorescence in ex vivo skin biopsies. Silencing of α3(V) collagen was performed using siRNA. The expression of MMP-9 was investigated using qPCR. RESULTS:In our study, we showed that α3(V) collagen was abundantly produced by basal skin keratinocytes and in the outer root sheath of the hair. α3(V) collagen expression appears to decrease with age in the skin and in differentiated keratinocytes. We also identified that treatment of keratinocytes and ex vivo skin biopsies with retinoic acid induced α3(V) collagen expression. Finally, we showed that inhibition of α3(V) collagen in keratinocytes led to an increase in MMP-9 expression. CONCLUSION:This study provides a better understanding of α3(V) collagen expression and localization in the skin. These findings suggest that α3(V) collagen could contribute to the therapeutic and anti-aging value of retinoic acid on the skin and may open new prospects. Finally, our data shed more light on the functional relationship between α3(V) collagen and MMP-9, opening possibilities for anti-aging and eczema treatments.

Since March 2013, animal testing for toxicity evaluation of cosmetic ingredients is banned in Europe. This directive applies to all personal care ingredients including oral ingredients. Gingival in vitro 3D models are commercially available. However, it is essential to develop “in house model” to modulate several parameters to study oral diseases, determine the toxicity of ingredients, test biocompatibility, and evaluate different formulations of cosmetic ingredients. Our expertise in tissue engineering allowed us to reconstruct human oral tissues from normal human gingival cells (fibroblasts and keratinocytes). Indeed, isolation from surgical leftover was performed to culture these gingival cells. These cells keep their endogenous capacity to proliferate allowing reconstruction of equivalent tissue close to in vivo tissue. Reconstruction of gingival epithelium, chorion equivalent, and the combination of these two tissues (full thickness) using primary gingival cells displayed all characteristics of an in vivo gingival model.

Intrinsic and extrinsic aging affect the health of human skin. Extracellular matrix protein degradation, DNA damage and oxidative stress are known to disturb skin architecture and skin homeostasis leading to skin aging. Traditional Chinese Medicine (TCM) delivers a large amount of knowledge regarding the phytotherapeutic power of diverse plants. Panax ginseng, Polygonatum cyrtonema, Epiphyllum oxypetalum, Nelumbo nucifera and Osmanthus fragrans are five plants used in TCM for their protective effect. In this study, several combinations of these TCM plants were explored: first, an in silico analysis was performed to predict their potential to target biological activities in the skin and then, some predictions were verified with in vitro studies to underline the synergistic effect of plant extracts. The results showed a stronger anti-aging activity for the combination with the five plants compared to the combination with Panax ginseng, Polygonatum cyrtonema, Epiphyllum oxypetalum and, compared to Panax ginseng alone.

The skin's primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary structures and components responsible for the skin's barrier function are susceptible to environmental variables, dermatological conditions, and the aging process. The ensuing alterations to structure, composition, and organizational attributes of the epidermal barrier can impact its integrity and functionality. The aim of this study was to assess the effect of a novel complex composed of a ceramide, energizing peptide, and Camu Camu extract (SUPCERATTM complex) on specific markers of epidermal barrier integrity, as well as epidermal and dermal function. All the experiments were conducted on fresh human abdominal skin explants. Intradermal production of hyaluronic acid, epidermal claudin-1, and ceramide synthase 3 expressions, as well as epidermal lipids content were assessed using specific fluorescent stainings on ex vivo skin after the application of the complex or placebo. Additionally, dermal elastase and collagenase activities were assessed using in tubo enzymatic assays. Lastly, the effect of a cosmetic cream containing SUPCERATTM complex was assessed using subjective Global Aesthetic Improvement Scale (GAIS) in a small cohort of patients after 60 days of use. The application of the SUPCERATTM complex on ex vivo skin led to significant increase in dermal hyaluronic acid content and epidermal activity of claudin-1, ceramide synthase 3 and epidermal ceramide content. Furthermore, in tubo enzymatic assays demonstrated inhibition of both dermal elastase and collagenase activities. In addition, the patient-reported results indicated significant improvements in skin quality and appearance.

OBJECTIVE:This study focused on the development of a new-to-world ingredient harnessing the natural potential of fresh Jasminum grandiflorum flowers to self-ferment by its phytobiome revealing flower content. Analytical investigations were conducted to highlight specific phytocompounds generated during the natural fermentation of flowers in comparison to a conventional extraction. The synergy with another extraction technology maximized the generation of biocompounds for an interesting efficacy. METHODS:Jasmine extract was elaborated by combining two patented technologies: the phytofermentology™, inspired by plant-microorganisms interaction and designed to develop ingredients obtained by natural fermentation of the vegetal using its own phytobiota; and the PSR™ technology allowing the extraction of bioactive phytocompounds such as small RNAs from plants. RESULTS:Analytical investigations of Jasmine extract highlighted uniqueness and richness of the phytocompound profiles, such as organics acids and phenolic compounds, markers of fermentation only obtained after phytofermentology in comparison to conventional extraction. Jasmine extract has the particularity to contain jasmintides, flower small peptides belonging to the family of cysteine-rich peptides (CRPs). Antioxidant and global anti-ageing properties were investigated in cell-free assays demonstrating interesting results: about 20% scavenging of free radicals from 0.5% of Jasmine extract and protection from DNA damage of 26% in comparison to a stressed control. CONCLUSION:Phytofermentology™ technology combined with PSR™ technology, meant to be respectful of the environment, allowed to development of biofunctionals very close to nature with a unique analytical signature as Jasmine extract, using the potential of fresh flowers phytobiota to self-ferment. The efficacy of the ingredient on global antioxidation and anti-ageing via hyaluronidase/tyrosinase inhibitions was highlighted by cell-free evaluation assays. Further and complementary studies should be conducted to confirm the bioefficacy of this ingredient with in vitro / ex vivo assays.

Solar radiation effects on the skin have been widely investigated for decades. Ultraviolet radiation(280–400nm) have been well described and characterized as the main cause responsible of photoaging. Moreover, the solar radiations comprise also infrared and visible light(400-700nm). Blue light(400-500nm) exhibits a broad range of beneficial as well as adverse effects, depending principally on the exposure time and the wavelength applied. Blue LED phototherapy is widely used to treat skin disorders like acne, psoriasis, atopic dermatitis or eczema. Conversely, deleterious effects were also reported, responsible of cutaneous photoaging. Most of them are based on blue light-induced oxidative stress, moreover, blue light exposure has also been shown to induce skin hyperpigmentation. A proprietary bioengineered 3D model of Reconstructed Human Pigmented Epidermis(RHPE) containing keratinocytes and melanocytes was used to study the impact of blue light irradiation on skin hyperpigmentation. First, we attempted to induce hyperpigmentation on different RHPE phototype using several irradiation protocols. We highlighted differences in skin morphology, melanin level and tyrosinase expression level in RHPE phototype III compared to RHPE phototype V after a 415 nm blue light irradiation. Indeed, the type III-RHPE exhibited a higher tyrosinase expression associated with an increase of melanin production. Some of key gene and miRNAs involved in melanogenesis, were investigated in this type III-RHPE, based on in silico study. We evaluated MITF level at different time following irradiations. Results showed an increase of MITF expression level with a peak 24 h after the first blue light exposition. We also observed an upstream modulation of several miRNAs of interest. The innovative hyperpigmented skin bioengineered model, obtained in this study following blue light exposure, represents a promising tool to identify biofunctional ingredients with modulatory potentialin vitroto limit cutaneous photoaging.

Objective: Throughout our existence, the skin senses and analyses the mechanical forces imposed by the environment. In response to these environmental forces, skin can deform itself and achieve a biological response. The subsequent cutaneous plasticity emerges from mechanical properties arising from the collective action of the skin cells, particularly keratinocytes, that govern the tensile strength via cell-to-cell adhesions and via cell-matrix adhesion structures. In addition to serving as force-bearing entities, keratinocytes respond to forces by activating signalling pathways to control their own fate and function. To detect and adapt to mechanical signals, keratinocytes possess a panel of sensory receptors and junctional intercellular structures. Mechanically activated ion channel Piezo1 has been described as a force sensor and as being involved in pleasant touch perception. In this study, relationships between Piezo1 modulation and oxytocin synthesis were investigated.Methods: The expression of Piezo1 in the skin was studied and compared with the expression of TRPV1. Dooku1 antagonist and Jedi1 agonist were used to modulate Piezo1. The level of E-cadherin and oxytocin was monitored in ex vivo skin biopsies by immunodetection.Results: Taken together, our results illustrate the major role of mechanosensitive ion channel Piezo1 in skin barrier integrity, and in peripheral oxytocin synthesis in the skin.Conclusion: In conclusion, this study highlights the relationships between pleasant touch, soft touch and local oxytocin synthesis.

This article presents an hybrid and hierarchical model in which two modeling and simulation approaches, discrete event system specification simulation (DEVS) and semantic technologies, were used together in order to help in the analysis of a major healthcare problem, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Indeed, the complexity of the SARS-CoV-2 replication process, and the range of hierarchical scales over which it interacts with cellular components (extending from genomic and transcriptomic to proteomic and metabolomic scales), and the intricate way in which they are interwoven, make its understanding very challenging. It is therefore crucial to model the different scales of the replication process, by taking into account all interactions with the infected cell. By combining the advantages of both DEVS simulation and ontological modeling, we propose a hierarchical ontology-based DEVS simulation model of the SARS-CoV-2 viral replication at both the micro-molecular (proteomic and metabolomic) and macro-molecular (genomic and transcriptomic) scales. First, we demonstrate the usefulness of combining DEVS simulation and semantic technologies in a common modeling framework to face the complexity of the SARS-CoV-2 viral replication at different scales. Second, the modeling and simulation of the SARS-CoV-2 replication process on different levels provide valuable information on the different stages of the virus's life cycle and lays the foundation for a system to anticipate future mutations selected by the virus.

Objective: This study explored the impact of a black tea extract obtained through (plant small RNA) PSR (TM) technology, characterized by its abundance of small molecules, particularly citric acid-an antioxidant and tricarboxylic acid (TCA) cycle contributor-on mitochondrial health. The primary focus was to assess whether this extract could counteract reactive oxygen species (ROS)-induced mitochondrial alterations associated with aging, which lead to impaired mitochondrial function, reduced ATP production, and increased ROS generation. Methods: The PSR (TM) extraction method was employed to obtain a high content of polyphenols and small molecules, particularly citric acid. Results: In comparison with a conventional extract, the PSRTM extract demonstrated significant enhancements in aconitase activity, an ROS-sensitive enzyme in the TCA cycle, as well as basal respiration and ATP synthesis in fibroblast cells and skin biopsies. Moreover, the PSR (TM) extract effectively reduced ROS production by safeguarding this critical enzyme within the Krebs cycle and displayed superior capabilities in scavenging free radicals when exposed to UV-induced stress. When administered post-UV exposure, the PSR (TM) extract protected nuclear DNA by reducing the formation of cyclobutane pyrimidine dimers (CPDs) and promoting DNA repair mechanisms. Furthermore, the extract exhibited beneficial effects on the extracellular matrix, characterized by a reduction in matrix metalloprotease 1 (MMP1) and an increase in fibrillin 1 expression. Conclusions: These findings collectively suggest that the PSR (TM) extract holds promising antiaging potential, potentially functioning as a mitochondrial nutrient/protector due to its multifaceted benefits on mitochondrial function, nuclear DNA integrity, and the extracellular matrix.

The production of active ingredients for cosmetic purposes can be impacted by supply chain disruption or by a strategic choice to upgrade an ingredient. Indeed, a product change must face the constraint of the raw material sourcing to find a more local and sustainable plant source. It can be an opportunity to valorize a by-product of the food industry as a cosmetic ingredient, and also adding value by relocating the entire production chain. Food byproducts are more and more known for their significant richness of bioactives phytocompounds with potential skin benefits. Green extractions technologies allowed to obtain value-added products. Upgrading natural cosmetic ingredients is an opportunity to improve manufacturing process while maintaining required specifications and efficacy, with improved sustainable profile. The main challenges were, first to find local sourcing of this apple byproduct, the new sourcing was provided by a local supplier. Then we founded a process to dry this atypical vegetal waste and thus guarantee the manufacturing feasibility. The process has been reworked on a laboratory scale to modify and improve it with the best yield. Analytical studies on phytochemicals composition were performed to validate the upgraded product. After validation of lab scale process, manufacturing transfer was done to perform industrial trial. Robustness and reproducibility of the process were significantly demonstrated with a better yield than the one obtained with the previous raw material. Analytical studies demonstrated that the new botanical extract showed similar characteristics and phytocompounds content such as triterpenoids as the targeted molecules of interest. Further studies had also confirmed antioxidant and global anti-aging properties of this product. Improving sustainability of our products is a constant objective. With this new version, we reach a step forward in that direction. In this regard, we are now able to supply a more sustainable version which meets essential global requirements.

Squalene (SQ) is a lipid produced in sebaceous gland involved in the vital skin barrier function. Its peroxidation leads to the accumulation of SQ epoxides and monohydroperoxides causing various skin damages as hyperpigmentation, wrinkles, and acne. Monitoring the effects of a cosmetic cream on the evolution of lipid content and their oxidation during clinical studies represent numerous analysis; highlighting the need to combine molecule analyses in a single method. High Performance Liquid Chromatography (HPLC) coupled with Diode Array Detector (DAD) commonly allowed to detect SQ but is not sensitive enough for detection of oxidation products. On the other hand, SQ structure cannot be detected by Mass Spectrophotometer (MS) although it is more sensitive. The aim of this study was to propose a method to analyze SQ and its oxidation products within a single injection by coupling DAD and MS analyses. First, SQ standard was oxidized with hydrogen peroxide. Separation of the unoxidized SQ and the oxidation products was developed by HPLC-DAD-MS. It allowed to detect unoxidized SQ standard with DAD at 210 nm and identification of SQ peroxidation products with MS in electrospray ionization negative scan mode at m/z=409 and m/z=425. Indeed, a method of 41 minutes, including DAD detection at 210 nm and MS in single ion monitoring mode detection at m/z=409 and m/z=425 was validated to study simultaneously squalene and its peroxidation products. Secondly, the method obtained was applied to monitor the evolution of SQ, collected with sebutapes, on volunteers after application of a cream containing 1% Santalum album extract.Results collected have allowed to demonstrate anti-oxidation effect of the ingredient against squalene peroxidation. In conclusion, we developed a method to monitor SQ and its oxidation products by HPLC-DAD-MS in a single shot. This new method allows to study squalene and squalene oxidation in the skin of volunteers, by a non-invasive manner.

Seborrheic dermatitis and dandruff are common chronic inflammatory skin diseases in the population. An innovative 3D human skin model reconstructed with specific scalp keratinocytes and colonized by M. restricta was developed to mimic this skin issue. In this model, efficacy of sclareolide, derived from a sustainable natural ingredient, was evaluated. After the reconstruction of human scalp epidermis displaying similar characteristic to human scalp, these tissues were colonized by M. restricta, a well-known yeast involved in dandruff. After several days of treatment, consequences were observed in terms of morphological modification, inflammatory response. Then sclareolide, a derivative ingredient from salvia sclarea, was evaluated on this in vitro model and validated with a clinical study. The human epidermis reconstructed from adult keratinocytes present all in vivo skin characteristics. This tissue was colonized with M. restricta in a specific environment enriched in triglycerides to preserve the bacteria activity and interaction with the human scalp cells. After this interaction, M. restricta disrupted barrier function and penetration of the superficial epidermal layers (granular layers) was observed by microscopic analysis inducing inflammatory response (IL8). The treatment with sclareolide avoid the disruption of barrier function and de facto decreased the inflammation of the scalp tissue. The anti-dandruff efficacy of sclareolide was confirmed by clinical study on volunteers.This in vitro model presented similar characteristics of human ex vivo scalp infected by the skin microbiome and more precisely by M. restricta regarding dandruff issues. Sclareolide, a sustainable ingredient obtained from Salvia sclarea, plays an important role in improving (reinforcing) skin barrier integrity, and in limiting skin inflammation induced by M. restricta infection. These results suggest the potential of sclareolide to be considered as an alternative to zinc pyrithione treatment.