Rational molecular design converting fascaplysin derivatives to potent broad-spectrum inhibitors against bacterial pathogens via targeting FtsZ.

The filamentous temperature-sensitive mutant Z protein (FtsZ), a key player in bacterial cell division machinery, emerges as an attractive target to tackle the plight posed by the ever growing antibiotic resistance over the world. Therefore in this regard, agents with scaffold diversities and broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens are highly needed. In this study, a new class of marine-derived fascaplysin derivatives has been designed and synthesized by Suzuki-Miyaura cross-coupling. Some compounds exhibited potent bactericidal activities against a panel of Gram-positive (MIC = 0.024-6.25 µg/mL) and Gram-negative (MIC = 1.56-12.5 µg/mL) bacteria including methicillin-resistant S. aureus (MRSA). They exerted their effects by dual action mechanism via disrupting the integrity of the bacterial cell membrane and targeting FtsZ protein. These compounds stimulated polymerization of FtsZ monomers and bundling of the polymers, and stabilized the resulting polymer network, thus leading to the dysfunction of FtsZ in cell division. In addition, these agents showed negligible hemolytic activity and low cytotoxicity to mammalian cells. The studies on docking and molecular dynamics simulations suggest that these inhibitors bind to the hydrophilic inter-domain cleft of FtsZ protein and the insights obtained in this study would facilitate the development of potential drugs with broad-spectrum bioactivities.

The study of the role of purified anti-mouse CD193 (CCR3) antibody in allergic rhinitis mouse animal models.

The pathogenesis of allergic asthma is similar to that of allergic rhinitis, with inflammation cells producing and releasing inflammatory mediators and cytokines closely related to CCR3.Based on the theory of "one airway, one disease", the use of CCR3 monoclonal antibody may have a similar effect on allergic rhinitis. However, there are few studies on CCR3 monoclonal antibody in allergic rhinitis. Therefore, the aim of this study was to investigate the effective concentration of CCR3 monoclonal antibody, to compare the effects of different methods of administration, and to examine the lung condition of allergic mice to investigate whether antibody treatment protects the lungs. In this study, we constructed a mouse model of allergic rhinitis and intraperitoneally injected different doses of CCR3 monoclonal antibody (5, 10, and 20 uL/mg) to observe its therapeutic effect: observing changes in tissue morphology of nasal mucosa, infiltration of inflammation, and using ELISA to detect changes in relevant inflammatory mediators and cytokines, studying the role of CCR3 mAb in inhibiting CCR3-related actions on the nasal mucosa of allergic rhinitis mice. Furthermore, In addition, the therapeutic effects of intraperitoneal injection (i.p.) and intranasal administration (i.n.) were studied on the basis of effective concentrations.