Targeted delivery of Fc-fused PD-L1 for effective management of acute and chronic colitis.

The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.

Preparation and Antioxidant Activities of High Fischer's Ratio Oligopeptides from Goat Whey.

This study aimed to obtain high Fischer's ratio oligopeptides from goat whey (HFO) and investigate antioxidant property of it. Hydrolysis of goat whey was done with the approach of sequential digestion of pepsin and flavourzyme. With the adsorption of aromatic amino acids by activated carbon, HFO with a Fischer's ratio of 27.070 and a molecular weight of 200-1,000 Da were obtained, and the branched-chain amino acids accounted for 22.87%. Then the antioxidant activity of HFO was evaluated. At the concentrations of 2.0 mg/mL and 0.50 mg/mL, HFO scavenged 77.27% and 99.63% of 1,1-diphenyl-2-picrylhydrazyl and 3-ethylbenzthiazoline-6-sulphonate free radicals respectively. The scavenging rate of HFO against hydroxyl radicals reached 92.31% at the concentration of 0.25 mg/mL. Animal experiments demonstrated that HFO could moderate the changes of malondialdehyde, superoxide dismutase and glutathione peroxidase caused by CCl4-induced oxidative stress in vivo. This study indicated that HFO from goat whey was capable of oxidation resistance both in vivo and in vitro, which provided a scientific basis for the high-value processing and application of goat milk whey.

Identification of Lesional Tissues and Nonlesional Tissues in Early Gastric Cancer Endoscopic Submucosal Dissection Specimens Using a Fiber Optic Raman System.

AIM: To identify lesional and nonlesional tissues from early gastric cancer (EGC) patients by Raman spectroscopy to build a diagnostic model and effectively diagnose EGC. METHOD: Specimens were collected by endoscopic submucosal dissection from 13 patients with EGC, and 55 sets of standard Raman spectral data (each integrated 10 times) were obtained using the fiber optic Raman system; there were 33 sets of lesional tissue data, including 18 sets of high-grade intraepithelial neoplasia (HGIN) data and 15 sets of adenocarcinoma data, and 22 sets of nonlesional tissue data. After the preprocessing steps, the average Raman spectrum was obtained. RESULTS: The nonlesional tissues showed peaks at 891 cm-1, 1103 cm-1, 1417 cm-1, 1206 cm-1, 1234 cm-1, 1479 cm-1, 1560 cm-1, and 1678 cm-1. Compared with the peaks corresponding to nonlesional tissues, the peaks of the lesional tissues shifted by different magnitudes, and a new characteristic peak at 1324 cm-1 was observed. Comparing the peak intensity ratio and the integral energy ratio of the lesional tissues with those of the nonlesional tissues revealed a significant difference between the two groups (independent-samplest-test, P < 0.05). Considering the peak intensity ratio of I1560 cm-1/I1103 cm-1 as a diagnostic indicator, the accuracy, sensitivity, and specificity of diagnosing EGC were 98.8%, 93.9%, and 91.9%, respectively. Considering the integral energy ratio (noncontinuous frequency band and continuous frequency band) as a diagnostic indicator, the accuracy, sensitivity, and specificity of diagnosing EGC were 99.2-99.6%, 93.9-97.0%, and 95.5%, respectively. CONCLUSIONS: The integral energy ratio of the Raman spectrum could be considered an effective indicator for the diagnosis of EGC.

The effect of heat treatment on the microstructure and functional properties of whey protein from goat milk.

This work investigated the effects of thermal processing methods commonly used in the dairy industry and prolonged treatment at different temperatures on the denaturation, microstructure, and functional properties of whey proteins (WP) from goat milk. The complete denaturation of WP was observed in goat milk treated at 85°C for 30 min, and at a higher temperature (>85°C), a considerable amount of WP was easily denatured. The low temperature, long time treatment had the least effect on the secondary structure, whereas ultra-high temperature treatment had the greatest effect, and the amount of regular structures decreased gradually with prolonged time. The most serious morphological damage occurred after treatment at 85°C for 30 min, which was consistent with the denaturation results. This result indicated that the denaturation degree, particle size, surface hydrophobicity, and microstructure had a strong influence on the functional properties of WP from goat milk after heat treatment. The heat treatment of goat milk at 65°C for 30 min and 85°C for 15 s increased the particle size, turbidity, zeta potential, and surface hydrophobicity of WP, and these increases ensured that the WP had a good emulsifying activity index, water-holding capacity, oil-holding capacity, foaming capacity, and foam stability. This study simulated the heat treatment conditions used in actual production, aiming to provide a theoretical basis for industry.

Comparative proteomics of goat milk during heated processing.

Milk proteins have shown to be very sensitive to heated processing. This study investigated the heat-dependent changes of goat milk proteins using label-free quantification (LFQ). A total of 843 proteins were identified in all the samples, of which 625 proteins were quantified. There were 527, 543, 537, 533 and 539 proteins quantified in the control group (CG) and heated groups (HGs: HG1, HG2, HG3 and HG4), respectively, and 438 proteins were common to all groups. The effects of high temperature/short time (HTST) treatment on proteins were similar to ultra-pasteurization (UP) and ultra-high temperature (UHT), but the low temperature/long time (LTLT) was different. Proteomics analysis demonstrated that heated processing increases the digestibility of proteins and is beneficial for anti-atherosclerosis therapy. These results expand the knowledge of the protein compositions from different heated processing. And it can further the utilization of the protein component of goat milk for human nutrition and health.