PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis is a chronic inflammatory hepatic disorder with no effective treatment. Mesenchymal stromal cells (MSCs) have emerged as a promising treatment owing to their unique advantages. However, their heterogeneity is hampering use in clinical applications. METHODS: Wharton's jelly derived MSCs (WJ-MSCs) were isolated from 58 human donors using current good manufacturing practice conditions. Gene expression profiles of the WJ-MSCs were analyzed by transcriptome and single-cell RNA-sequencing (scRNA-seq), and subsequent functional differences were assessed. Expression levels of programmed death-ligand 1 (PD-L1) were used as an indicator to screen WJ-MSCs with varied immunomodulation activities and assessed their corresponding therapeutic effects in a mouse model of concanavalin A-induced autoimmune hepatitis. RESULTS: The 58 different donor-derived WJ-MSCs were grouped into six gene expression profile clusters. The gene in different clusters displayed obvious variations in cell proliferation, differentiation bias, trophic factor secretion, and immunoregulation. Data of scRNA-seq revealed four distinct WJ-MSCs subpopulations. Notably, the different immunosuppression capacities of WJ-MSCs were positively correlated with PD-L1 expression. WJ-MSCs with high expression of PD-L1 were therapeutically superior to WJ-MSCs with low PD-L1 expression in treating autoimmune hepatitis. CONCLUSION: PD-L1 expression levels of WJ-MSCs could be regarded as an indicator to choose optimal MSCs for treating autoimmune disease. These findings provided novel insights into the quality control of MSCs and will inform improvements in the therapeutic benefits of MSCs.

Identification of high iron-chelating peptides with unusual antioxidant effect from sea cucumbers and the possible binding mode.

Iron deficiency anemia (IDA) is a common nutritional disease affecting 2 billion people. To develop a new iron-fortified food, we designed a novel type of iron-chelating peptide [Sea cucumbers peptides (SCP)-Fe] from sea cucumbers. SCP can chelate ferrous ions. The neutral protease hydrolysate have the highest iron chelating activity (117.17 ± 2.62 mg/g). Single factors including pH, material ratio, and molecular weight, had a significant effect on the iron chelating activity. The characterization of the SCP-Fe chelate revealed a loose and blocky structure with increased particle size. The amino acid composition, peptide identification and molecular docking indicated that Asp, Glu, Gly and Pro played an important role in binding to ferrous ions. After chelation, SCP-Fe chelate had dual nutrition effects of stronger radical scavenging ability and potential high-efficiency iron supplementation ability. These results might provide insights into the methods for developing functional foods such as iron-fortified seafood.

Release of bound polyphenols from wheat bran soluble dietary fiber during simulated gastrointestinal digestion and colonic fermentation in vitro.

Dietary fiber can act as a carrier of bound phenolics in the distal tracts of the gut, where potential microbial processing occurs, but specific mechanism is unclear. This study aimed to evaluate the release characteristic and activity of bound polyphenols from wheat bran soluble dietary fiber (SDF) during simulated gastrointestinal digestion and colonic fermentation in vitro. The result suggested that the bioaccessibility of bound polyphenols in colonic fermentation was 7.42 times that in gastrointestinal digestion stage. Gallic acid, p-hydroxybenzoic acid and vanillic acid were the most abundant polyphenol metabolites after the fermentation for 6 h. The released phenolics exhibited strong radical scavenging activity (DPPH, 99.22 ± 2.05 µmol TE/100 g DW; ABTS, 330.27 ± 3.56 µmol TE/100 g DW). Fecal fermentation of SDF significantly reduced the value of F/B and stimulated the growth of beneficial bacteria, such as Bacteroides, Akkermansia, and Faecalibacterium. Therefore, bound polyphenols may maintain gut health through their prebiotic activity.

A real-time, dynamic early-warning model based on uncertainty analysis and risk assessment for sudden water pollution accidents.

A real-time, dynamic, early-warning model (EP-risk model) is proposed to cope with sudden water quality pollution accidents affecting downstream areas with raw-water intakes (denoted as EPs). The EP-risk model outputs the risk level of water pollution at the EP by calculating the likelihood of pollution and evaluating the impact of pollution. A generalized form of the EP-risk model for river pollution accidents based on Monte Carlo simulation, the analytic hierarchy process (AHP) method, and the risk matrix method is proposed. The likelihood of water pollution at the EP is calculated by the Monte Carlo method, which is used for uncertainty analysis of pollutants' transport in rivers. The impact of water pollution at the EP is evaluated by expert knowledge and the results of Monte Carlo simulation based on the analytic hierarchy process. The final risk level of water pollution at the EP is determined by the risk matrix method. A case study of the proposed method is illustrated with a phenol spill accident in China.