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BACKGROUND: Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like fever. People with the syndrome develop serious allergies, ranging from rashes to anaphylaxis or shock. The few available studies on mosquito venom immunotherapy have utilized whole-body preparations and small sample sizes. Still, owing to their little success, vaccination remains a promising alternative as well as a permanent solution for infections like Skeeter's. METHODS: This study, therefore, illustrated the construction of an epitope-based vaccine candidate against Skeeter Syndrome using established immunoinformatic techniques. We selected three species of mosquitoes, Anopheles melas, Anopheles funestus, and Aedes aegypti, to derive salivary antigens usually found in mosquito bites. Our construct was also supplemented with bacterial epitopes known to elicit a strong TH1 response and suppress TH2 stimulation that is predicted to reduce hypersensitivity against the bites. RESULTS: A quality factor of 98.9496, instability index of 38.55, aliphatic index of 79.42, solubility of 0.934747, and GRAVY score of -0.02 indicated the structural (tertiary and secondary) stability, thermostability, solubility, and hydrophilicity of the construct, respectively. The designed Aedes-Anopheles vaccine (AAV) candidate was predicted to be flexible and less prone to deformability with an eigenvalue of 1.5911e-9 and perfected the human immune response against Skeeter (hypersensitivity) and many mosquito-associated diseases as we noted the production of 30,000 Th1 cells per mm3 with little (insignificant production of Th2 cells. The designed vaccine also revealed stable interactions with the pattern recognition receptors of the host. The TLR2/vaccine complex interacted with a free energy of - 1069.2 kcal/mol with 26 interactions, whereas the NLRP3/vaccine complex interacted with a free energy of - 1081.2 kcal/mol with 16 molecular interactions. CONCLUSION: Although being a pure in-silico study, the in-depth analysis performed herein speaks volumes of the potency of the designed vaccine candidate predicting that the proposition can withstand rigorous in-vitro and in-vivo clinical trials and may proceed to become the first preventative immunotherapy against mosquito bite allergy.
Asunto(s)
Aedes , Anopheles , Epítopos , Hipersensibilidad , Mordeduras y Picaduras de Insectos , Animales , Mordeduras y Picaduras de Insectos/inmunología , Mordeduras y Picaduras de Insectos/prevención & control , Anopheles/inmunología , Aedes/inmunología , Epítopos/inmunología , Hipersensibilidad/prevención & control , Hipersensibilidad/inmunología , Vacunas/inmunología , HumanosRESUMEN
Chimaphila umbellata has been studied for almost two centuries now, with the first paper exploring the phytochemistry of the plant published in 1860. Almost all contemporary studies focus on the biotechnological advances of C. umbellata including its utilization as a natural alternative in the cosmetic, food, biofuel, and healthcare industry, with a special focus on its therapeutic uses. This literature review critically investigates the significance and applications of secondary metabolites extracted from the plant and presses on the biotechnological approaches to improve its utilization. C. umbellata is home to many industrially and medicinally important phytochemicals, the majority of which belong to phenolics, sterols, and triterpenoids. Other important compounds include 5-hydroxymethylfurfural, isohomoarbutin, and methyl salicylate (the only essential oil of the plant). Chimaphilin is the characteristic phytochemical of the plant. This review focuses on the phytochemistry of C. umbellata and digs into their chemical structures and attributes. It further discusses the challenges of working with C. umbellata including its alarming conservation status, problems with in-vitro cultivation, and research and development issues. This review concludes with recommendations based on biotechnology, bioinformatics, and their crucial interface.
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Copper oxide nanoparticles (CuO NPs) have received increasing interest due to their distinctive properties, including small particle size, high surface area, and reactivity. Due to these properties, their applications have been expanded rapidly in various areas such as biomedical properties, industrial catalysts, gas sensors, electronic materials, and environmental remediation. However, because of these widespread uses, there is now an increased risk of human exposure, which could lead to short- and long-term toxicity. This review addresses the underlying toxicity mechanisms of CuO NPs in cells which include reactive oxygen species generation, leaching of Cu ion, coordination effects, non-homeostasis effect, autophagy, and inflammation. In addition, different key factors responsible for toxicity, characterization, surface modification, dissolution, NPs dose, exposure pathways and environment are discussed to understand the toxicological impact of CuO NPs. In vitro and in vivo studies have shown that CuO NPs cause oxidative stress, cytotoxicity, genotoxicity, immunotoxicity, neurotoxicity, and inflammation in bacterial, algal, fish, rodents, and human cell lines. Therefore, to make CuO NPs a more suitable candidate for various applications, it is essential to address their potential toxic effects, and hence, more studies should be done on the long-term and chronic impacts of CuO NPs at different concentrations to assure the safe usage of CuO NPs.