María-José Fábrega

Apremilast (APM) is a novel drug for the treatment of psoriasis and psoriatic arthritis. APM is a phosphodiesterase 4 (PDE4) inhibitor, raising intracellular cAMP levels and thereby decreasing the inflammatory response by modulating the expression of TNF-α, IL-17, IL-23, and other inflammatory cytokines. The goal of this study is to develop APM gels as a new pharmaceutical formulation for the treatment of topical psoriasis. APM was solubilized in Transcutol-P and incorporated into Pluronic F127, Sepigel, and carbomer bases at different proportions. All formulations were characterized physiochemically. A biopharmaceutical study (release profile) was performed, and ex vivo permeation was evaluated using a human skin model. A toxicity assay was carried out on the HaCaT cell line. A mouse model of imiquimod-induced psoriasis skin inflammation was carried out to determine its efficacy by histological analysis, RNA extraction, and RT-qPCR assays. APM gel formulations showed good physicochemical characteristics and a sustained release profile. There was no permeation of any gel measured through human skin, indicating a high retained amount of APM on the skin. Cell viability was greater than 80% at most dilution concentrations. APM gels treated the psoriasis mouse model, and it shows a reduction in the proinflammatory cytokines (IL-8, IL-17A, IL-17F, and IL-23). APM gels could be a new approach for the treatment of topical psoriasis.

Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been associated with the development of acne vulgaris, while other phylotypes have been linked to healthy skin. In this scenario, bacterial extracellular vesicles (EVs) play a role in the interkingdom communication with the human host. The purpose of this study was to examine the impact of EVs generated by various phylotypes of C. acnes on inflammation and sebum production using different in vitro skin cell types. The main findings of this study reveal that the proteomic profile of the cargo embodied in the EVs reflects distinct characteristics of the different C. acnes phylotypes in terms of life cycle, survival, and virulence. The in vitro skin cell types showed an extended pro-inflammatory modulation of SLST A1 EVs consistently triggering the activation of the inflammation-related factors IL-8, IL-6, TNFα and GM-CSF, in comparison to SLST H1 and SLST H2. Additionally, an acne-prone skin model utilizing PCi-SEB and arachidonic acid as a sebum inducer, was employed to investigate the impact of C. acnes EVs on sebum regulation. Our findings indicated that all three types of EVs significantly inhibited sebum production after a 24-h treatment period, with SLST H1 EVs exhibiting the most pronounced inhibitory effect when compared to the positive control. The results of this study highlight the protective nature of C. acnes SLST H1 EVs and their potential use as a natural treatment option for alleviating symptoms associated with inflammation and oily skin.

Essential oils are a complex mixture of aromatic substances whose pharmacological actions, including antimicrobial, antioxidant, anticancer, and anti-inflammatory activities, have been widely reported. This study aimed to evaluate the anti-Candida and dermal anti-inflammatory activity of essential oils from native and cultivated Ecuadorian plants. Essential oils from Bursera graveolens, Dacryodes peruviana, Mespilodaphne quixos, and Melaleuca armillaris were isolated by hydrodistillation and were characterized physically and chemically. Its tolerance was analyzed by in vitro and in vivo studies. The antifungal activity was studied against Candida albicans, Candida glabrata, and Candida parapsilosis, whereas the anti-inflammatory effect was evaluated by a mouse ear edema model. The main compounds were limonene, α-phellandrene, (E)-methyl cinnamate, and 1,8-cineole, respectively. All essential oils showed high tolerability for skin application, antifungal activity against the three Candida strains, and anti-inflammatory efficacy by decreasing edema and overexpression of pro-inflammatory cytokines. Dacryodes peruviana essential oil showed the highest antifungal activity. On the other hand, Dacryodes peruviana and Melaleuca armillaris showed the greatest anti-inflammatory potential, decreasing edema by 53.3% and 65.25%, respectively, and inhibiting the overexpression of TNF-α, IL-8, IL-17A, and IL-23. The results suggest that these essential oils could be used as alternative therapies in the treatment of both cutaneous candidiasis and dermal inflammation.

Background: Cutibacterium acnes (C. acnes) is one of the most prevalent bacteria that forms the human skin microbiota. Specific phylotypes of C. acnes have been linked to acne vulgaris development, while others have been found in individuals with healthy skin. In this scenario, bacterial extracellular vesicles (EVs) play an interkingdom communication role with the host. The purpose of this study was to examine the impact of EVs generated by various phylotypes of C. acnes on inflammation and sebum production using different in vitro skin models. Results: The main findings of this study reveal that the proteomic profile of the cargo embodied in the EVs reflects distinct characteristics of the different C. acnes phylotypes in terms of lifestyle, survival, and virulence. The in vitro skin models showed an extended pro-inflammatory modulation of A1 EVs consistently triggering the activation of the inflammation-related factors IL-8, IL-6, TNFαand GM-CSF, in comparison to H1 and H2. Additionally, an acne-prone skin model utilizing PCi-SEB and arachidonic acid (AA) as a sebum inductor, was employed to investigate the impact of C. acnes EVs on sebum regulation. The results indicated that all three types of EVs significantly inhibited sebum production after a 24-hour treatment period, with H1 EVs exhibiting the most pronounced inhibitory effect when compared to the positive control. Conclusions: The results of this study highlight the protective nature of C. acnes H1 EVs and their potential as a natural treatment option for alleviating symptoms associated with inflammation and oily skin.

Background: Cutibacterium acnes ( C. acnes ) is one of the most prevalent bacteria that form the human skin microbiota and, depending on multifactorial conditions it can help to maintain the skin homeostasis. Actually, different phylotypes of C. acnes have been associated with different degrees of acne vulgaris development, while others, such as the H1 subtype, have been detected in patients with non-acneic skin. However, due to the physiology of the skin, the skin microbiota neither has direct access to the skin’s sebaceous glands nor to the main immune cells, as they are protected by a sebum layer. Therefore, the inter-kingdom communication relies on secreted factors and bacterial extracellular vesicles (EVs). In this context, the purpose of this project was to study the role of EVs secreted by three different phylotypes of C. acnes (A1 as pathogenic, H1 as beneficial and H2 as commensal). Results: Main findings showed that the proteomic profile of the cargo embodied in the EVs reflects unique characteristics of the different C. acnes phylotypes in terms of lifestyle, survival and virulence. Moreover, in vitro skin models showed an extended pro-inflammatory modulation of A1 EVs, while H1 EVs displayed a high sebum-reducing potential. Conclusions: This study has highlighted the role of C. acnes EVs as key modulators during skin alterations, specially H1 EVs as an alternative based-natural treatment to fight acne vulgaris symptomatology.

Essential oils are natural aromatic substances that contain complex mixtures of many volatile compounds frequently used in pharmaceutical and cosmetic industries. Dacryodes peruviana (Loes.) H.J. Lam is a native species from Ecuador whose anti-inflammatory activity has not been previously reported, thus the aim of this study was to evaluate the anti-inflammatory activity of D. peruviana essential oil. To that end, essential oil from D. peruviana fruits was isolated by hydrodistillation and characterized physically and chemically. The tolerance of the essential oil was analyzed by cytotoxicity studies using human keratinocytes. The anti-inflammatory activity was evaluated by an arachidonic acid-induced edema model in mouse ear. The predominant compounds in D. peruviana essential oil were α-phellandrene, limonene, and α-pinene, with the three compounds reaching approximately 83% of the total composition. Tolerance studies showed high biocompatibility of this essential oil with human keratinocytes. In vivo studies demonstrated a moisturizing effect and an alleviation of several events occurred during the inflammatory process after topical treatment with D. peruviana essential oil such as decline in skin edema; reduction in leukocytic infiltrate; and decrease in inflammatory cytokines TNFα, IL-8, IL-17A, and IL-23. Therefore, this essential oil could be an attractive treatment for skin inflammation.

In the past few years, new bacterial-cell-free transcription–translation systems have emerged as potent and quick platforms for protein production as well as for prototyping of DNA regulatory elements, genetic circuits, and metabolic pathways. The Gram-positive commensal Cutibacterium acnes is one of the most abundant bacteria present in the human skin microbiome. However, it has recently been reported that some C. acnes phylotypes can be associated with common inflammatory skin conditions, such as acne vulgaris, whereas others seem to play a protective role, acting as possible “skin probiotics”. This fact has made C. acnes become a bacterial model of interest for the cosmetic industry. In the present study we report for the first time the development and optimization of a C. acnes-based cell-free system (CFS) that is able to produce 85 μg/mL firefly luciferase. We highlight the importance of harvesting the bacterial pellet in mid log phase and maintaining CFS reactions at 30 °C and physiological pH to obtain the optimal yield. Additionally, a C. acnes promoter library was engineered to compare coupled in vitro TX-TL activities, and a temperature biosensor was tested, demonstrating the wide range of applications of this toolkit in the synthetic biology field.

Cutibacterium acnes is the most abundant bacterium living in human, healthy and sebum-rich skin sites, such as the face and the back. This bacterium is adapted to this specific environment and therefore could have a major role in local skin homeostasis. To assess the role of this bacterium in healthy skin, this review focused on (i) the abundance of C. acnes in the skin microbiome of healthy skin and skin disorders, (ii) its major contributions to human skin health, and (iii) skin commensals used as probiotics to alleviate skin disorders. The loss of C. acnes relative abundance and/or clonal diversity is frequently associated with skin disorders such as acne, atopic dermatitis, rosacea, and psoriasis. C. acnes, and the diversity of its clonal population, contributes actively to the normal biophysiological skin functions through, for example, lipid modulation, niche competition and oxidative stress mitigation. Compared to gut probiotics, limited dermatological studies have investigated skin probiotics with skin commensal strains, highlighting their unexplored potential.