The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective:To optimize the formula of metronidazole and borneol sustained-release films. Methods: The mass ratio of Rhizoma Bletillae polysaccharide and polyvinyl alcohol 124(PVA-124) and the dosage of glycerol and sodium carboxymethyl cellulose ( CMC-Na) as the influencing factors ,the appearance of films and the release rate of metronidazole at 0. 5h and 4h as the comprehen-sive evaluation indices, the formula of the film-forming materials was optimized by orthogonal test. Results:The mass ratio of Rhizoma Bletillae polysaccharide and PVA-124 was the key factor affecting the quality of the films. When the mass ratio of Rhizoma Bletillae pol-ysaccharide and PVA-124 was 20∶80, and the dosage of glycerol was 3. 5g and that of CMC-Na was 0. 14g, the appearance of the films was satisfied, the release rate of metronidazole at 0. 5h and 4h was 25. 17% and 69. 64%, respectively, and the average cumulative re-lease rate at 8h was over 90%. Conclusion:The films prepared by the optimized formula are flat, smooth, clean and moderately soft, which can not only remain the drug release characteristics of the films made by the original formula, but also exhibit the pharmacologi-cal effect of Rhizoma Bletillae.

AIM: To investigate the damages of adrenal gland in rabbits infected with neisseria meningococci(MC).METHODS: 18 rabbits were injected with MC (1×1011 organism/kg, iv, model group, n=10) or normal saline (control group, n=8).TNF-α was detected in baseline (before challenged), 60 min and 120 min after injection. 120 min after injection, TNF-α immunochemical localization of adrenal gland was detected with ABC methods by electron microscopy. RESULTS: In model group, TNF-α positive cells were located in medulla and TNF-α released into simus of medulla. The medulla damages were appeared but gland cells of cortex was normal. No damages were showed in control group. TNF-α value of plasm was elevated at 60 min and 120 min after injection compared with control group. CONCLUSION: TNF-α was released into medulla and resulted in medulla damages after MC challenging. Adrenal cortex didnt damaged in early phase of MC septic shock.

AIM: To investigate the effect of epigallocatechin-3-gallate (EGCG) on lipopolysaccharide (LPS)-induced p38 MAPK activation and tumor necrosis factor-? (TNF-?) secretion in macrophages. METHODS: Western blotting was used to detect the phosphorylation of p38 MAPK in mouse macrophages cultured in vitro. Enzyme linked immunosorbent assay was used to determine the secretion of TNF-? in macrophages. Electron microscopy was used to study the effect of EGCG on the structure of LPS. RESULTS: LPS caused activation of p38 MAPK and more production of TNF-?, EGCG inhibited LPS-induced phosphorylation of p38 MAPK and TNF-? production and had no effect on the structure of LPS. CONCLUSIONS: EGCG has no direct effect on LPS, but blocks cellular signal pathway. The inhibition of EGCG on LPS-induced TNF-? production is mediated, at least in part, through blocking of p38 MAPK pathway. [

AIM: To investigate the damages of adrenal gland in rabbits infected with neisseria meningococci(MC).METHODS: 18 rabbits were injected with MC (1?10 11 organism/kg, iv, model group, n=10 ) or normal saline (control group, n=8 ).TNF-? was detected in baseline (before challenged), 60 min and 120 min after injection. 120 min after injection, TNF-? immunochemical localization of adrenal gland was detected with ABC methods by electron microscopy. RESULTS: In model group, TNF-? positive cells were located in medulla and TNF-? released into simus of medulla. The medulla damages were appeared but gland cells of cortex was normal. No damages were showed in control group. TNF-? value of plasm was elevated at 60 min and 120 min after injection compared with control group. CONCLUSION: TNF-? was released into medulla and resulted in medulla damages after MC challenging. Adrenal cortex didnt damaged in early phase of MC septic shock. [