Plasma Exosomes Aggravate Acute Pancreatitis by Promoting M1 Polarization of Adipose Tissue Macrophages in Obesity-Related Severe Acute Pancreatitis.

BACKGROUND AND AIMS: Obesity may be a risk factor for severe acute pancreatitis (SAP). However, its precise mechanism is not yet fully understood. METHODS: We fed rats with a standard laboratory diet (SLD) and a high-fat diet (HFD). SAP model rats were established by retrograde injection of sodium taurocholate. Serum non-esterified fatty acids (NEFAs), lipase (LPS), and myeloperoxidase (MPO) were measured, as were adipose IL-1, IL-6, IL-10, and TNF-α levels. HE staining was performed to determine the severity of pancreatitis. Serum exosomes were extracted from rats with obesity-related SAP, verified by transmission electron microscopy (TEM) and western blot analysis, and co-cultured with THP-1 cells. Flow cytometry was used to analyze the M1 and M2 phenotypes of macrophages in adipose tissues and THP-1 cells. Q-PCR was used to analyze the levels of IL-1, IL-6, IL-10, and TNF-α in each group of cells. RESULTS: The body weight and serum NEFA concentrations of rats in the HFD group were significantly higher than those in the SLD group. Adipose tissue macrophages in the HFD group exhibited a higher percentage of the M1 type than those in the SLD group. The severity of pancreatitis were significantly increased in the HFD + SAP group. Pro-inflammatory macrophages and cytokines were significantly higher in the HFD + SAP group and THP-1 cells co-cultured with serum exosomes extracted from rats with obesity-related SAP. CONCLUSIONS: Obesity might worsen the severity of pancreatitis by amplifying the immune response and activating M1 polarization in adipose tissue macrophages via serum exosomes in rats of obesity-related SAP. In our study, we isolated exosomes from the serum of mice with obesity-related SAP. After inducing THP-1 cells to become M0-typed macrophages, we co-cultured the cells with exosomes and observed that exosomes from obesity-related SAP increased the proportion of M1-typed macrophages and promoted the release of pro-inflammatory factors such as IL-1, IL-6, and TNF. Therefore, obesity might worsen the severity of pancreatitis by amplifying the immune response and activating M1 polarization in adipose tissue macrophages via serum exosomes in rats of obesity-related SAP.

Elevated serum iron level is a predictor of prognosis in ICU patients with acute kidney injury.

BACKGROUND: Accumulation of iron is associated with oxidative stress, inflammation, and regulated cell death processes that contribute to the development of acute kidney injury (AKI). We aimed to investigate the association between serum iron levels and prognosis in intensive care unit (ICU) patients with AKI. METHODS: A total of 483 patients with AKI defined as per the Kidney Disease: Improving Global Guidelines were included in this retrospective study. The data was extracted from the single-centre Medical Information Mart for Intensive Care III database. AKI patients with serum iron parameters measured upon ICU admission were included and divided into two groups (low group and high group). The prognostic value of serum iron was analysed using univariate and multivariate Cox regression analysis. RESULTS: The optimal cut-off value for serum iron was calculated to be 60 µg/dl. Univariable Cox regression analysis showed that serum iron levels were significantly correlated with prognosis of AKI patients. After adjusting for possible confounding variables, serum iron levels higher than 60 µg/dl were associated with increases in 28-day (hazard [HR] 1.832; P <  0.001) and 90-day (HR 1.741; P <  0.001) mortality, as per multivariable Cox regression analysis. CONCLUSIONS: High serum iron levels were associated with increased short- and long-term mortality in ICU patients with AKI. Serum iron levels measured upon admission may be used for predicting prognosis in AKI patients.

Red blood cell distribution width is associated with mortality risk in patients with acute respiratory distress syndrome based on the Berlin definition: A propensity score matched cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder of the lungs and is associated with oxidative damage. However, red blood cell distribution width (RDW), as an indicator of body response to inflammation and oxidative stress, has not been studied for its relationship with ARDS as diagnosed by the Berlin definition. OBJECTIVES: To examine the value of RDW in predicting the prognosis of in patients with ARDS. METHODS: This is a retrospective study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Berlin-defined ARDS patients using mechanical ventilation for more than 48 hours were selected using structured query language. The primary statistical methods were propensity score matching and sensitivity analysis, including an inverse probability weighting model to ensure the robustness of our findings. RESULTS: A total of 529 intensive care unit (ICU) patients with ARDS according to the Berlin definition were enrolled in the study. The adjusted OR showed an adverse effect between the higher RDW group and 30-day mortality [OR 2.33, 95% CI (1.15-4.75), P=0.019]. However, we found that length of ICU stay was not related to RDW (P=0.167), and in the anaemia group, RDW was poorly predictive of 30-day mortality (P=0.307). CONCLUSION: In unselected ARDS patients, higher RDW was associated with higher 30-day mortality rate. Further investigation is required to validate this relationship with prospectively collected data.