Combined metabolomic and proteomic analysis of sepsis related acute liver injury and its pathogenesis research.

BACKGROUND: Sepsis-induced acute liver injury is common in patients in intensive care units. However, the exact mechanism of this condition remains unclear. The purpose of this study was to investigate the roles and mechanisms of proteins and metabolites in the liver tissue of mice after sepsis and elucidate the molecular biological mechanisms of sepsis-related liver injury. METHODS: First, a lipopolysaccharide (LPS)-induced sepsis mouse model was established. Then, according to alanine aminotransferase (ALT) and aspartate aminotransferase (AST) detection in mouse serum and liver histopathological examination (HE) staining, the septic mice were divided into two groups: acute liver injury after sepsis and nonacute liver injury after sepsis. Metabolomics and proteomic analyses were performed on the liver tissues of the two groups of mice to identify significantly different metabolites and proteins. The metabolomics and proteomics results were further analysed to identify the biological indicators and pathogenesis related to the occurrence and development of sepsis-related acute liver injury at the protein and metabolite levels. RESULTS: A total of 14 differentially expressed proteins and 46 differentially expressed metabolites were identified. Recombinant Erythrocyte Membrane Protein Band 4.2 (Epb42) and adenosine diphosphate (ADP) may be the key proteins and metabolites responsible for sepsis-related acute liver injury, according to the correlation analysis of proteomics and metabolomics. The expression of the differential protein Epb42 was further verified by western blot (WB) detection. CONCLUSIONS: Our study suggests that the differential protein Epb42 may be key proteins causing sepsis-associated acute liver injury, providing new and valuable information on the possible mechanism of sepsis-associated acute liver injury.

Causal relationship between gut Prevotellaceae and risk of sepsis: a two-sample Mendelian randomization and clinical retrospective study in the framework of predictive, preventive, and personalized medicine.

Objective: Gut microbiota is closely related to sepsis. Recent studies have suggested that Prevotellaceae could be associated with intestinal inflammation; however, the causal relationship between Prevotellaceae and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut Prevotellaceae and sepsis could provide opportunity for targeted prevention and personalized treatment. Methods: The genome-wide association study (GWAS) summary-level data of Prevotellaceae (N = 7738) and sepsis were obtained from the Dutch Microbiome Project and the UK Biobank (sepsis, 1380 cases; 429,985 controls). MR analysis was conducted to estimate the associations between Prevotellaceae and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of Prevotellaceae in sepsis patients to explore the relationship between Prevotellaceae relative abundance and the 28-day mortality. Results: Genetic liability to f__Prevotellaceae (OR, 1.91; CI, 1.35-2.71; p = 0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median Prevotellaceae relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%, p < 0.001). Multivariate analysis confirmed that Prevotellaceae relative abundance (OR, 1.10; CI, 1.03-1.22; p = 0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that Prevotellaceae relative abundance (AUC: 0.787, 95% CI: 0.671-0.902, p = 0.0003) could predict the prognosis of sepsis patients. Conclusion: Our results revealed that Prevotellaceae was causally associated with sepsis and affected the prognosis of sepsis patients. These findings may provide insights to clinicians on developing improved sepsis PPPM strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00340-6.

Early gut microbiological changes and metabolomic changes in patients with sepsis: a preliminary study.

The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

Changes in the microbiota in different intestinal segments of mice with sepsis.

Introduction: The small intestine, as the main digestion and absorption site of the gastrointestinal tract, is often overlooked in studies, and the overall microbiota does not reflect the makeup of the microbiota in different segments of the intestine. Therefore, we aimed to exclude the influence of routine ICU treatment measures on sepsis patients and observed changes in the diversity and abundance of gut microbiota in different intestinal segments of septic mice. Methods: The mice were randomly divided into the CLP6h group and the sham group. The contents of the colon and small intestine of the experimental group and the control group were collected after 6 h. Results: After CLP, the number and structure of the gut microbiota in the colon changed most obviously, among which Bacteroidetes had the most significant changes. Akkermansia, D.Firmicutes_bacterium_M10_2, Blautia, Bifidobacterium, Lactobacillus, Candidatus_Arthromitus, and Muribaculaceae were changed in the colon. Lactobacillus, Bifidobacterium, Akkermansia, Blautia, Candidatus_Arthromitus, and Lachnospiraceae_NK4A136_group were changed in the small intestine. Discussion: Our experiment found that there were different numbers of unique and common gut microbiota in the small intestine and colon after sepsis, and the gut microbiota of the colon changed more drastically after sepsis than the small intestine. Thus, we should focus on protective gut microbiota and mucin-degrading microbes. We hope that these results will provide help for sepsis treatment in the future.

Enhanced corrosion resistance and bonding strength of Mg substituted ß-tricalcium phosphate/Mg(OH)2 composite coating on magnesium alloys via one-step hydrothermal method.

To overcome the defect of high degradation rate of magnesium (Mg), bioactive coatings with compact structure, sufficient bonding strength and enhanced corrosion resistance are essential for Mg-based biodegradable implants. In this study, a dense Mg-substituted ß-tricalcium phosphate and magnesium hydroxide (ß-TCMP/Mg(OH)2) composite coating was prepared on AZ31 alloy via one-step hydrothermal method. The influences of hydrothermal temperature on its composition, microstructure of the surface and interface, bonding strength and corrosion behavior were evaluated. The results showed that the compact composite coating synthesized at 140 °C not only possessed a crack-free bilayered structure with an adequate bonding strength (more than 20.88 ±â€¯1.60 MPa), but also got an extreme high impedance (1197.003 ±â€¯152.817 kΩ cm2) so that significantly enhanced the corrosion resistance and inhibited the formation of pitting corrosion. Furthermore, the in vitro immersion test suggested that the composite coating slower the initial degradation rate of Mg alloys and enhanced its surface bioactivity to some extent.

Re-evaluation of pathogens causing Valsa canker on apple in China.

Valsa canker is a destructive disease on apple that causes serious economic losses in eastern Asia. In the present study fungal isolates from cankered apple and pear bark were examined and compared with morphology and rDNA-ITS sequences. Valsa mali was confirmed to be an independent species and a causal pathogen of Valsa canker on apple and pear in China. It was the predominant species (96.7% of isolates) on apple and was complemented by V. malicola (3.3% of isolates). Significant intraspecific genetic differentiation was detected in V. mali with two varieties recognized, V. mali var. mali occurring exclusively on apple and V. mali var. pyri occurring on both apple and pear. Results from genetic analysis and cross-inoculation tests provided support for the hypothesis that host preference probably catalyzed such genetic changes within the pathogen populations.