RESUMO
BACKGROUND: Photodamage to the skin stands out as one of the most widespread epidermal challenges globally. Prolonged exposure to sunlight containing ultraviolet radiation (UVR) instigates stress, thereby compromising the skin's functionality and culminating in photoaging. Recent investigations have shed light on the importance of autophagy in shielding the skin from photodamage. Despite the acknowledgment of numerous phytochemicals possessing photoprotective attributes, their potential to induce autophagy remains relatively unexplored. PURPOSE: Diminished autophagy activity in photoaged skin underscores the potential benefits of restoring autophagy through natural compounds to enhance photoprotection. Consequently, this study aims to highlight the role of natural compounds in safeguarding against photodamage and to assess their potential to induce autophagy via an in-silico approach. METHODS: A thorough search of the literature was done using several databases, including PUBMED, Science Direct, and Google Scholar, to gather relevant studies. Several keywords such as Phytochemical, Photoprotection, mTOR, Ultraviolet Radiation, Reactive oxygen species, Photoaging, and Autophagy were utilized to ensure thorough exploration. To assess the autophagy potential of phytochemicals through virtual screening, computational methodologies such as molecular docking were employed, utilizing tools like AutoDock Vina. Receptor preparation for docking was facilitated using MGLTools. RESULTS: The initiation of structural and functional deterioration in the skin due to ultraviolet radiation (UVR) or sunlight-induced reactive oxygen species/reactive nitrogen species (ROS/RNS) involves the modulation of various pathways. Natural compounds like phenolics, flavonoids, flavones, and anthocyanins, among others, possess chromophores capable of absorbing light, thereby offering photoprotection by modulating these pathways. In our molecular docking study, these phytochemicals have shown binding affinity with mTOR, a negative regulator of autophagy, indicating their potential as autophagy modulators. CONCLUSION: This integrated review underscores the photoprotective characteristics of natural compounds, while the in-silico analysis reveals their potential to modulate autophagy, which could significantly contribute to their anti-photoaging properties. The findings of this study hold promise for the advancement of cosmeceuticals and therapeutics containing natural compounds aimed at addressing photoaging and various skin-related diseases. By leveraging their dual benefits of photoprotection and autophagy modulation, these natural compounds offer a multifaceted approach to combatting skin aging and related conditions.
RESUMO
BACKGROUND: Candida tropicalis causes tropical invasive fungal infections, with a high mortality. This fungus has been found to be resistant to antifungal classes such as azoles, echinocandins, and polyenes in several studies. As a result, it is vital to identify novel approaches to prevent and treat C. tropicalis infections. In this study, an in silico technique was utilized to deduce and evaluate a powerful multivalent epitope-based vaccine against C. tropicalis, which targets the secreted aspartic protease 2 (SAP2) protein. This protein is implicated in virulence and host invasion. RESULTS: By focusing on the Sap2 protein, 11 highly antigenic, non-allergic, non-toxic, and conserved epitopes were identified. These were subsequently paired with RS09 and flagellin adjuvants, as well as a pan HLA DR-binding epitope (PADRE) sequence to create a vaccine candidate that elicited both cell-mediated and humoral immune responses. It was projected that the vaccine design would be soluble, stable, antigenic, and non-allergic. Ramachandran plot analysis was applied to validate the vaccine construct's 3-dimensional model. The vaccine construct was tested (at 100 ns) using molecular docking and molecular dynamics simulations, which demonstrated that it can stably connect with MHC-I and Toll-like receptor molecules. Based on in silico studies, we have shown that the vaccine construct can be expressed in E. coli. We surmise that the vaccine design is unrelated to any human proteins, indicating that it is safe to use. CONCLUSIONS: The vaccine design looks to be an effective option for preventing C. tropicalis infections, based on the outcomes of the studies. A fungal vaccine can be proposed as prophylactic medicine and could provide initial protection as sometimes diagnosis of infection could be challenging. However, more in vitro and in vivo research is needed to prove the efficacy and safety of the proposed vaccine design.