Candidiasis is often observed in immunocompromised patients and is the 4th most common cause of bloodstream infections. However, antifungals are limited, so novel antifungal agents are urgently needed. Antimicrobial peptides (AMPs) are considered as potential alternatives of conventional antibiotics. In the present study, antimicrobial peptide protonectin was chemically synthesized and its antifungal activity and mode of action were studied. Our results showed that protonectin has potent antifungal activity and fungicidal activity against the tested fungi cells. Its action mode involved the disruption of the membrane integrity and the inducing of the production of cellular ROS. Furthermore, protonectin could inhibit the formation of biofilm and kill the adherent fungi cells. In conclusion, with the increase of fungal infection, protonectin may offer a new strategy and be considered as a potential therapeutic agent against fungal disease.

Antimicrobial peptide has the potential to be developed as new kind of antimicrobial agents with novel action mechanism. However, the susceptibility to protease is a drawback for potential peptides to be clinical used. d-amino acid substitution can be one way to increase the proteolytic stability of peptides. In the present study, we synthesized the d-lysines substituted analog (d-lys-MPI) and the d-enantiomer of polybia-MPI (D-MPI) to improve the proteolytic resistance of polybia-MPI. Our results showed that, the stability of its d-amino acid partially substituted analog d-lys-MPI was increased. However, it lost antimicrobial activity at the tested concentration with the loss of α-helix content. As shown in the CD spectra, after substitution, the spectra of D-MPI is symmetrical to MPI, indicated it turned into left hand α-helical conformation. Excitingly, the stability of D-MPI toward the tested protease was improved greatly. Notably, the antimicrobial activity of D-MPI was comparable to its L-counterpart MPI, even improved. In addition, the hemolytic activity of D-MPI was lowered. This also indicated that the action target of antimicrobial peptide polybia-MPI was not chiral specific. So, D-MPI may offer a therapeutic strategy to defend the infection of microbes, considering its stability to protease and relatively lower cytotoxicity to human erythrocytes.

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A Cinchona alkaloid-derived squaramidecatalyzed asymmetric cycloaddition of trfluoromethyl-containing azomethine ylides with b-nitroalkenes was realized under mild conditions.Aserieso fb iologically important 5'-trifluoromethyl-spiro[pyrrolidin-3,2'-oxindoles] was synthesizede fficiently by this process in excellent yields,e nantioseletivities and diastereoselectivities.

Epithelial-mesenchymal transition (EMT) is essential in asthma airway remodeling. IL-33 from epithelial cells is involved in pulmonary fibrosis. CD146 has been extensively explored in cancer-associated EMT. Whether IL-33 regulates CD146 in the EMT process associated with asthma airway remodeling is still largely unknown. We hypothesized that EMT in airway remodeling was regulated by the IL-33/CD146 axis. House dust mite (HDM) extract increased the expression of IL-33 and CD146 in epithelial cells. Increased expression of CD146 in HDM-treated epithelial cells could be blocked with an ST2-neutralizing antibody. Moreover, HDM-induced EMT was dependent on the CD146 and TGF-β/SMAD-3 signaling pathways. IL-33 deficiency decreased CD146 expression and alleviated asthma severity. Similarly, CD146 deficiency mitigated EMT and airway remodeling in a murine model of chronic allergic airway inflammation. Furthermore, CD146 expression was significantly elevated in asthma patients. We concluded that IL-33 from HDM extract-treated alveolar epithelial cells stimulated CD146 expression, promoting EMT in airway remodeling in chronic allergic inflammation.