Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.

This study synthesizes carbon dots derived from crude extracts of purple sweet potato (CPP-CDs) and evaluates its anti-inflammatory effects in a lipopolysaccharide (LPS) -induced acute inflammation model. Characterization revealed that CPP-CDs possess a uniform spherical structure and excellent photoluminescent properties. In vitro, CPP-CDs significantly inhibited the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), reduced the accumulation of reactive oxygen species (ROS), suppressed pyroptosis, and facilitated the polarization of macrophages from the M1 phenotype to the M2 phenotype. In vivo, CPP-CDs significantly improved the survival rates of LPS-treated mice, mitigated tissue damage, and suppressed the levels of pro-inflammatory cytokines. Mechanistic studies indicated that CPP-CDs exert anti-inflammatory effects through the inhibition of the TLR4/NF-κB signaling pathway and the modulation of the NLRP3 inflammasome. Additionally, CPP-CDs exhibited excellent biocompatibility, with no significant toxicity observed in mice. This study provides strong evidence supporting the application of CPP-CDs as a novel anti-inflammatory material, highlighting their potential for acute inflammation treatment and expanding the possibilities for the development of carbon-dot-based anti-inflammatory therapies.

Background: Ventilator-associated pneumonia (VAP) is one of the common critical complications of nosocomial infection (NI) in invasive mechanically ventilated intensive care unit (ICU) patients. The efficacy of total parenteral nutrition (TPN), enteral nutrition and/or adjuvant peripheral parenteral nutrition (EPN) supplemented with or without probiotic, prebiotic, and synbiotic therapies in preventing VAP among these patients has been questioned. We aimed to systematically and comprehensively summarize all available studies to generate the best evidence of VAP prevention for invasive mechanically ventilated ICU patients.Methods: Randomized controlled trials (RCTs) for the administration of TPN, EPN, probiotics-supplemented EPN, prebiotics-supplemented EPN, and synbiotics-supplemented EPN for VAP prevention in invasive mechanically ventilated ICU patients were systematically retrieved from four electronic databases. The incidence of VAP was the primary outcome and was determined by the random-effects model of a Bayesian framework. The secondary outcomes were NI, ICU and hospital mortality, ICU and hospital length of stay, and mechanical ventilation duration. The registration number of Prospero is CRD42020195773.Results: A total of 8339 patients from 31 RCTs were finally included in network meta-analysis. The primary outcome showed that probiotic-supplemented EPN had a higher correlation with the alleviation of VAP than EPN in critically invasive mechanically ventilated patients (odds ratio [OR] 0.75; 95% credible intervals [CrI] 0.58–0.95). Subgroup analyses showed that probiotic-supplemented EPN prevented VAP in trauma patients (OR 0.30; 95% CrI 0.13–0.83), mixed probiotic strain therapy was more effective in preventing VAP than EPN therapy (OR 0.55; 95% CrI 0.31–0.97), and low-dose probiotic therapy (less than 10¹⁰ CFU per day) was more associated with lowered incidence of VAP than EPN therapy (OR 0.16; 95% CrI 0.04–0.64). Secondary outcomes indicated that synbiotic-supplemented EPN therapy was more significantly related to decreased incidence of NI than EPN therapy (OR 0.34; 95% CrI 0.11–0.85). Prebiotic-supplemented EPN administration was the most effective in preventing diarrhea (OR 0.05; 95% CrI 0.00–0.71).Conclusion: Probiotic supplementation shows promise in reducing the incidence of VAP in critically invasive mechanically ventilated patients. Currently, low quality of evidence reduces strong clinical recommendations. Further high-quality RCTs are needed to conclusively prove these findings.Systamatic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020195773], identifier [CRD42020195773].

Observational studies have linked gut microbiota (GM) to acute respiratory distress syndrome (ARDS), but the cause-and-effect relationship is yet to be determined. We acquired the latest genome-wide association study (GWAS) summary statistics on GM taxa from the German (N = 8956), Dutch (N = 7738), and MibioGen (N = 18,340) consortium GWAS catalogs, as well as ARDS (N _case = 431, N _control = 4,93,301) GWAS summary statistics from the FinnGen consortium. We employed Mendelian randomization (MR) analysis using inverse-variance weighted, MR-Egger, weighted mode, and weighted median methods to investigate the causal link between GM and ARDS. We used a Bonferroni correction to account for statistical bias resulting from repeated comparisons in order to control for false positive outcomes during multiple hypothesis testing. Meta-analyses were conducted to enhance the statistical power of the MR analysis. GM had no statistically significant impact on ARDS with Bonferroni correction. Actinobacteria , Proteobacteria , Bifidobacteriales , Bifidobacteriaceae , Rikenellaceae , Dorea , Streptococcus , Bilophila wadsworthia , Escherichia unclassified , OTU99_17 ( Parabacteroides ), TestASV_7 ( Bacteroides ), TestASV_26 ( Phascolarctobacterium ), and TestASV_43 ( Parasutterella ) are notable GM taxa with low uncorrected MR inverse-variance weighted P -values, potentially indicating a reduced risk of ARDS. Bifidobacterium longum , OTU99_30 ( Parasutterella ), and TestASV_16 ( Bacteroides ) are potentially linked to an increased risk of ARDS. Meta-analyses based on 3 GWAS summary statistics suggested that Streptococcus was potentially indicating a reduced risk of ARDS (odds ratio 0.610; 95% confidence interval 0.430–0.870; P = .006). These associations were proven to be robust through analyses of sensitivity, heterogeneity, and horizontal pleiotropy. From a genetic perspective, our findings suggest a potential relationship between the GM and ARDS rather than definitive causality. Given possible confounding and methodological constraints, the results should be interpreted with caution. Additional studies are needed to elucidate underlying mechanisms and clarify microbial interactions within the GM.