Palmatine ameliorated lipopolysaccharide-induced sepsis-associated encephalopathy mice by regulating the microbiota-gut-brain axis.

BACKGROUND: Sepsis-associated encephalopathy (SAE), a common neurological complication from sepsis, is widespread among patients in intensive care unit and is linked to substantial morbidity and mortality rates, thus posing a substantial menace to human health. Due to the intricate nature of SAE's pathogenesis, there remains a dearth of efficacious therapeutic protocols, encompassing pharmaceutical agents and treatment modalities, up until the present time. Palmatine exhibits distinctive benefits in the regulation of inflammation for the improvement of sepsis. Nevertheless, the precise functions of palmatine in treating SAE and its underlying mechanism have yet to be elucidated. PURPOSE: This study aimed to evaluate efficiency of palmatine in SAE mice and its underlying mechanisms. STUDY DESIGN AND METHODS: Behavioral experiments, percent survival rate analysis, histological analysis, immunofluorescence staining, ELISA analysis, were performed to evaluate the efficiency of palmatine in SAE mice. Quantibody® mouse inflammation array glass chip was performed to observe the effects of palmatine on inflammation storm in SAE mice. Real-time quantitative and western blotting analyzes were employed to examine the expression of relevant targets in the Notch1/nuclear factor-kappa B (NF-κB) pathway. Finally, brain tissues metabolomics-based analyzes were performed to detect the differentially expressed metabolites and metabolic pathways. The fecal samples were subjected to microbial 16S rRNA analysis and untargeted metabolomics analysis in order to identify the specific flora and metabolites associated with SAE, thereby further investigating the mechanism of palmatine in SAE mice. RESULTS: Our results showed that palmatine significantly improved nerve function, reduced cell apoptosis in brain tissue, and decreased inflammatory cytokine levels in SAE induced-LPS mice. Meanwhile, our results demonstrate the potential of palmatine in modulating key components of the Notch1/NF-κB pathway, enhancing the expression of tight junction proteins, improving intestinal permeability, promoting the growth of beneficial bacteria (such as Lachnospiraceae_NK4A136_group), inhibiting the proliferation of harmful bacteria (such as Escherichia-Shigella), and mitigating metabolic disorders. Ultimately, these observed effects contribute to the therapeutic efficacy of palmatine in treating SAE. CONCLUSION: The findings of our study have provided confirmation regarding the efficacy of palmatine in the treatment of SAE, thereby establishing a solid foundation for further exploration into SAE therapy and the advancement and investigation of palmatine.

Impact of susceptibility profiles of Gram-negative bacteria before and after the introduction of ertapenem at a medical center in northern Taiwan from 2004 to 2010.

This retrospective observational study evaluated the impact of antimicrobial consumption on antimicrobial susceptibility among aerobic Gram-negative bacteria after introducing ertapenem to the formulary of a teaching hospital (1130 beds) in northern Taiwan. Data on consumption of various antimicrobial agents, expressed as defined daily dose/1000 patient-days (DDD/1000 PD), were collected retrospectively from hospital pharmacy records 2 years before and 5 years after the introduction of ertapenem (October 2005). During the study period, the consumption of ampicillin and aminoglycosides decreased significantly. In contrast, the consumption of cefoxitin, ceftazidime, cefpirome, piperacillin-tazobactam, carbapenems (ertapenem, imipenem, and meropenem), and fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) increased significantly over time. There was a significant increase in the rate of susceptibility of Escherichia coli to ampicillin, cefotaxime, ceftazidime, piperacillin-tazobactam, cefpirome, amikacin, and levofloxacin; an increase in the rate of susceptibility of Klebsiella pneumoniae to ceftazidime, cefepime, cefpirome, piperacillin-tazobactam, meropenem, levofloxacin, and amikacin; a significant decrease in the rate of susceptibility of Pseudomonas aeruginosa to meropenem; and a significant decrease in the rate of susceptibility of Acinetobacter baumannii to ceftazidime, carbapenems, ciprofloxacin, and levofloxacin. The rate of antibiotic susceptibility to ertapenem of extended spectrum ß-lactamase producers, including E. coli and K. pneumoniae, remained stable. Usage of ertapenem was found to be negatively and significantly associated with the susceptibility rates of P. aeruginosa to meropenem and gentamicin. Significantly negative correlations were noted between the use of ertapenem and the rates of susceptibility of A. baumannii to ceftazidime, piperacillin-tazobactam, carbapenems (imipenem and meropenem), ciprofloxacin, and levofloxacin.