Restoration of intestinal mucosal in Euphorbia kansui-treated severe acute pancreatitis rats is based on HMGB1/MFG-E8 expression

Background: The pathogenesis of severe acute pancreatitis (SAP) is mediated substantially by dysfunctions in the intestinal barrier. Euphorbia kansui (EK) is a medicinal plant used widely in traditional Chinese medicine to treat inflammation; however, its efficacy and mechanism of action in SAP treatment is not yet well understood. Objective: To investigate the role of EK in intestinal barrier tissue repair and in the pathogenesis and development of SAP. Methods: The rat SAP model was established by a retrograde injection of sodium taurocholate into the pancreatic bile duct. The SAP model group and the SAP + EK treatment groups were divided into 6 subgroups according to timing: 2, 6, 12, 24, 48, or 72 h after inducing SAP. The progression of the SAP rats and of the rats receiving the EK treatment was evaluated using the ascites volume, serum amylase and plasma endotoxin levels, and histological grading of intestinal mucosal damage. In addition, serum inflammatory factor contents were measured using enzyme-linked immunosorbent assay (ELISA) tests and apoptotic cells in damaged ileum tissue were detected using TUNEL staining. Apoptosis markers and other signaling proteins in intestinal mucosal cells were detected by immunohistochemical assays and then validated by combining these data with quantitative polymerase chain reactions and western blotting. Results: Compared with the results of the SAP model rats, the results of the rats that received EK treatment demonstrated that EK could effectively reduce the ascites volume and serum amylase and plasma endotoxin levels. EK treatment also greatly reduced the abnormal intestinal morphological alterations in the rat SAP model and significantly downregulated the serum contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. EK treatment inhibited the elevation of capapse-3, inhibited the decrease of the Bcl-2 protein, and decreased the number of apoptotic cells in rat ileum tissue. Finally, EK treatment abrogated the increase of HMGB1 and the suppression of MFG-E8 protein expression in the SAP + EK rat ileum tissue. Conclusion: EK suppresses SAP pathogenesis by restoring intestinal barrier function and modulating the HMGB1/MFG-E8 signaling axis.

Establishing a stable platform for the measurement of blood endotoxin levels in the dialysis population

BackgroundGram-negative lipopolysaccharides are potent inducers of inflammation and have been shown to be present in patients with end-stage kidney disease. There are a variety of different manufacturers and assay types to quantify endotoxin levels; however, there is no standard methodology to demonstrate its presence in plasma.MethodsA control group consisting of haemodialysis and non-kidney disease was selected. Five sets of experiments were conducted to try and ascertain the best platform for plasma endotoxin testing. This included: testing of blank tubes; the effects of freezing, thawing and storage on recovery; the effect of different buffers; use of an endpoint assay and comparison of turbidimetric vs. chromogenic kinetic assays.ResultsNo endotoxin was detected in the blood collection tubes. Freezing and thawing per se did not affect spike recovery rates. However, the sequencing of sample dilution relative to freezing had a significant effect on endotoxin recovery. Buffers increased spike recovery at all levels of dilution. No endotoxin was demonstrated with either the turbidimetric or chromogenic kinetic assay at two different dilutions in the haemodialysis controls. The endpoint assay at a 1:5 dilution did not achieve a valid standard curve.ConclusionsThe findings of our study suggest that, when testing plasma samples, either a turbidimetric or chromogenic assay may be used and should be diluted with appropriate buffers to achieve optimal recovery. Studies looking to quantify the presence of plasma endotoxin need to internally validate their assays and specify their validation findings in their results.

Association of intestinal permeability with admission vitamin D deficiency in patients who are critically ill

Emerging data have led to the hypothesis that vitamin D plays a role in promoting epithelial barrier dysfunction. Therefore, intestinal permeability becomes a significant determiner in the future of patients hospitalized in intensive care unit (ICU). The relationship between vitamin D and intestinal permeability remains unclear in patients who are critically ill. The aim of the study is to document the relationship between the admission vitamin D deficiency and markers of intestinal permeability in the critical care setting. This was a single-center, observational, prospective study in the general ICU of a university-affiliated hospital. A sample of 144 ICU-hospitalized adult patients was recruited between January and May 2018. The admission serum 25-hydroxyvitamin D levels were measured and categorized as <20 and ≥20 ng/dL, respectively. Moreover, the admission plasma endotoxin and zonulin concentrations as markers of intestinal permeability were determined in stringent conditions. The association between markers of intestinal permeability and 25-hydroxyvitamin D levels was assessed adjusting for potential confounders through an estimation of a binary logistic regression model. Our results showed that median plasma endotoxin and zonulin decreased with increasing serum levels of vitamin D categories (p=0.001) in the overall study population. Multivariate binary logistic regression analyses showed a significant association between the plasma endotoxin (OR 0.12, 95% CI 0.03 to 0.52) and zonulin (OR 0.91, 95% CI 0.87 to 0.99) levels with serum levels of vitamin D categories in the overall population. Our finding suggests a relationship between vitamin D deficiency and early alterations in intestinal permeability. Thus, evaluating vitamin D levels in patients who are critically ill may be warranted.

Correction: Isoleucine attenuates infection induced by E. coli challenge through the modulation of intestinal endogenous antimicrobial peptide expression and the inhibition of the increase in plasma endotoxin and IL-6 in weaned pigs

Correction for ‘Isoleucine attenuates infection induced by E. coli challenge through the modulation of intestinal endogenous antimicrobial peptide expression and the inhibition of the increase in plasma endotoxin and IL-6 in weaned pigs’ by Man Ren et al., Food Funct., 2019, DOI: 10.1039/c9fo00218a.

Isoleucine attenuates infection induced byE. colichallenge through the modulation of intestinal endogenous antimicrobial peptide expression and the inhibition of the increase in plasma endotoxin and IL-6 in weaned pigs

Enteric infection is a major cause of morbidity and mortality in both humans and animals worldwide.

Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.