Therefore there is increasing demand for a novel compound to treat fungal infections

The function of CABIT domains remains to be elucidated, our study clearly demonstrated that the two CABIT domains in Themis are pivotal and serve distinct roles in its function for driving T cell development. The incidence rates of infectious diseases caused by pathogenic fungi have been increasing rapidly. Widespread fungal diseases not only affect plants but also threaten animal and human health, with morbidity and mortality critically influenced by superficial and invasive fungal infections. Particular attention has been paid to invasive fungal infections, which have a high mortality rate of more than 50%. Each year, at least 1.5 million people die from invasive fungal infections worldwide. The most frequently isolated human pathogenic fungi are Cryptococcus, Candida, and Aspergillus LY294002 inhibitor species, which normally cause diseases in patients with immunodeficiency due to human immunodeficiency virus infections or immunosuppressive medications for organ transplantation. Among these commonly isolated fungal pathogens, Cryptococcus neoformans causes cryptococcal meningitis and kills at least 650,000 patients annually throughout the world. Cryptococcal infections have a reported mortality rate of 20–70%. Currently available antifungal agents mostly target DNA and RNA synthesis, the biosynthesis of the cell wall component 1,3-bD-glucan, the ergosterol biosynthetic pathway, or ergosterol itself. Triazole, which inhibits the ergosterol biosynthetic pathway, is the most widely used fungistatic agent because of its effectiveness and safety. Fluconazole has been used extensively to treat superficial and invasive fungal infections. However, the number of resistant strains to currently available antifungal agents has increased dramatically during the last decade. The mechanism of resistant strains is through increased drug efflux or alteration of the drug target or target pathway, which reduces drug efficacy. Plant extracts have been used as an effective source of antifungal agents. Vanillin is a good example, which is a primary component of the vanilla bean extract. Vanillin has long been used as a flavoring compound and is generally recognized as safe. Each year, more than 12,000 tons of vanillin is consumed, but the compound is mainly synthetically produced because the naturally derived product is expensive. Because of its safety and long-established use as a food additive, a number of studies have investigated the potential of vanillin as an antifungal agent. However, no report has shown promising efficacy of vanillin against fungi. Lopez-Malo et al. and Cerrutti and Alzamora suggested a possible use of vanillin as an antifungal agent in food preservation. However, its inhibitory concentration was too high to be promising. A recent study by Faria et al. also found no growth inhibitory activity of vanillin on nine reference human pathogenic fungal strains of Candida and C. neoformans.

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