Cysteine carboxyethylation generates neoantigens to induce HLA-restricted autoimmunity.

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4+ T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4+ T cell responses and autoantibody production in autoimmune diseases.

Effect of type 2 diabetes on liver images of GD-EOB-DTPA-enhanced MRI during the hepatobiliary phase.

To analyze alterations of the liver appearance during the hepatobiliary phase of individuals with type 2 diabetes who are receiving gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI). Fifty-seven individuals who received Gd-EOB-DTPA-enhanced MRI and had normal liver and renal function but did not have (control group) or have type 2 diabetes (observation group) were retrospectively included in this study. The liver enhancement ratio (LER) and contrast between liver parenchyma and portal vein (LPC) were calculated from hepatobiliary phase images. Utilizing liver to kidney signal intensity, signs of the biliary system, and signs of the portal vein, a functional liver imaging score (FLIS) was calculated. Wilcoxon rank-sum test was used to assess the between-group differences in LER, LPC, and FLIS. FLIS constituent ratios between the two groups were tested using the χ2 test. The effectiveness of LER, LPC, and FLIS for identifying type 2 diabetes was assessed by receiver operating characteristic curves (ROCs). The interobserver consistency of FLIS was evaluated using the intraclass correlation coefficients. The observation group's LER and LPC were lower than the control group. The constituent ratio of the FLIS score (liver to kidney signal intensity, p = 0.011) showed a significant between-group difference. According to ROCs, LER and LPC were associated with the identification of type 2 diabetes. LER = 0.54 and LPC = 1.46 were the optimal cutoff for identifying type 2 diabetes, respectively. FLIS demonstrated excellent inter-reader agreement. The relative signal intensity of the liver during the hepatobiliary phase is decreased in patients with type 2 diabetes. This should be considered when individuals with type 2 diabetes undergo Gd-EOB-DTPA-enhanced MRI to avoid misdiagnoses, such as small hepatocellular carcinoma or abnormal liver function.

Dietary Grape Seed Proanthocyanidin Alleviates the Liver Injury Induced by Long-Term High-Fat Diets in Sprague Dawley Rats.

In mammals, the liver is the most important organ that plays a vital function in lipid metabolism. Grape seed proanthocyanidin (GSPE) is a kind of natural polyphenolic compound primarily obtained from grape skin and seeds. Recent research found it had high bioavailability in defending against obesity, hyperlipidemia, inflammatory, oxidative stress, and targeting liver tissue. However, the mechanism of GSPE in regulating obesity induced by dietary high-fat (HF) was not fully understood, particularly the influences on liver functions. Therefore, this study aimed to investigate the effects of GSPE supplementation on the liver function and lipid metabolic parameters in rats fed HF diets long-term. A total of 40 healthy female Sprague Dawley rats were selected. After 8 weeks of obesity model feeding, the rats were randomly divided into four treatments: NC, standard diet; NC + GSPE, standard diet + 500 mg/kg body weight GSPE; HF, high-fat diet; HG + GSPE, high fat diet + 500 mg/kg body weight GSPE. Results indicated that long-term HF feeding caused severe liver problems including megalohepatia, steatosis, inflammation, and hepatocyte apoptosis. The supplementation of GSPE alleviated these symptoms. The results of the current experiment confirmed that GSPE addition up-regulated the expression of the Wnt3a/ß-catenin signaling pathway, thereby restraining the liver cell endoplasmic reticulum stress and hepatocyte apoptosis. Furthermore, the microRNA-103 may play a role in this signal-regulated pathway. In summary, GSPE had a protective effect on the liver and the current experiment provided a reference for the application of GSPE in animal nutrition as a kind of natural feed additive.

Comparison of organic acids supplementation on the growth performance, intestinal characteristics and morphology, and cecal microflora in broilers fed corn-soybean meal diet.

OBJECTIVE: The aim of this study was to compare the effects of three kinds of organic acid (OA) products on the growth performance, intestinal characteristics and morphology, and cecal microflora in broilers fed a corn-soybean meal meal diet. METHODS: A total of 420 one-day-old male Cobb 500 broilers with an average initial body weight of 49.11±1.02 g were used in this 42-day experiment. Birds were randomly allotted to one of five treatments (7 replicates with 12 birds per replicate). Treatments consisted of negative control (NC), basal diet; positive control (PC), basal diet+100 mg/kg of Aviramycin; OA1, basal diet+500 mg/kg of OA product 1; OA2, basal diet+1,000 mg/kg of OA product 2; and OA3, basal diet+1,200 mg/kg of OA product 3. RESULTS: The results indicated that OA product addition had no effect on growth performance parameters, such as body weight gain, feed intake, and feed conversion ratio, from days 1 to 14, 15 to 28, and 0 to 42, or on the pH values of the intestine, intestinal weight, or intestinal weight to body weight ratio. The intestinal morphology in terms of villus height and crypt depth were affected by dietary supplementation of OA products, respectively. Furthermore, dietary addition of OAs had positive influences on the maintenance of the cecal microflora based on the results of 16S rRNA analysis. CONCLUSION: Dietary inclusion of three kinds of OA products all benefit broilers, but the mode of action may be different. This study provides a basis for the application of OA products used in the poultry industry.

Effects of Microbial Phytase Supplementation on Egg Production and Egg Quality in Hy-line Brown Hens During the Late Laying Period.

The objective of this study was to evaluate the effects of microbial phytase on egg production and egg quality in older hens. A total of 216, 63-week-old Hy-line brown laying hens were distributed in a randomized complete design 10-week feeding trial of 3 dietary treatments with 12 replications per treatment and 6 hens per replication. The 3 dietary treatments were corn-soybean meal-based diets supplemented with 0% (CON), 0.06% (TRT1), and 0.12% (TRT2) microbial phytase. Significantly higher hen-day egg production was observed in the TRT1 treatment compared to CON (P<0.05), except during the first two weeks of the experiment. During weeks 3, 4, and 9, TRT2 had a greater hen-day egg production percentage than CON (P<0.05). The damaged egg ratio was not affected. The egg quality parameters (e.g., eggshell color, eggshell strength, albumen height, egg weight, and the Haugh unit) were affected by microbial phytase supplementation (P<0.05). However, there were no significant effects on the eggshell thickness and yolk color. In conclusion, microbial phytase supplementation to the diets of older hens could improve production performance, extend the peak laying period, and alter the egg quality parameters.

Evaluation of Achyranthes japonica Nakai extract on growth performance, nutrient utilization, cecal microbiota, excreta noxious gas emission, and meat quality in broilers fed corn-wheat-soybean meal diet.

This study was conducted to investigate the effects of dietary supplementation of Achyranthes japonica Nakai (AJN) extract as a natural feed additive on growth performance, nutrient utilization, cecal microbiota, excreta noxious gas emission, and meat quality in broilers fed corn-wheat-soybean meal diet. In total, seven hundred twenty 1-day-old male Ross 308 broilers with an average body weight (BW) of 43.36 ± 1.42 g were used in a 35-d feeding trial. Broilers were randomly assigned to 1 of the 4 treatments. Each treatment had 10 replication pens with 18 birds per replication. Dietary treatments composed of corn-wheat-soybean meal-based diets along with the addition of 0, 0.025, 0.05, and 0.1% of AJN extract. The BW gain and feed conversion rate were linearly influenced (P < 0.05) by the supplementation of AJN extract during days 8 to 21, 22 to 35, and the overall experiment. At the end of the experiment, the digestibility of dry matter and nitrogen and the population of cecal lactic acid bacteria were linearly improved (P < 0.05) in response to increasing AJN extract supplementation. Excreta emission of ammonia showed a linear decrease (P < 0.05) with the increasing levels of AJN extract. The breast muscle percentage linearly increased (P < 0.05) in birds fed AJN extract contained diets. In summary, the inclusion of AJN extract in corn-wheat-soybean meal diet improved growth performance, nutrient utilization, intestinal microbiota balance, and breast meat production and decreased excreta ammonia emission, which confirmed the applicability of AJN extract as a natural feed additive in broilers.

Evaluation of Weissella Cibaria JW15 Probiotic Derived from Fermented Korean Vegetable Product Supplementation in Diet on Performance Characteristics in Adult Beagle Dog.

This study was conducted to evaluate the effects of dietary supplementation of Weissella cibaria JW15 (WJW15) isolated from traditional Korean fermented vegetable product (kimchi) as a probiotic feed additive on nutrient digestibility, blood profiles, feces noxious gas emission, and feces Escherichia coli and Lactobacillus counts in adult Beagle dogs. In total, 15 Beagle dogs with an average initial body weight of 10.20 ± 0.38 kg were randomly assigned into three dietary treatments in a 14-day feeding trial. Dietary treatments consisted of basal diet (CON); MJW = CON + 50 g of WJW15 (3.0 × 108 cfu/g); and BJW = CON + 50 g WJW15 (3.0 × 109 cfu/g). At the end of the experiment, the serum concentration of triglycerides and feces ammonia emissions were decreased (P < 0.05) with the increasing level of WJW15 supplementation. High-density lipoprotein cholesterol in serum and feces lactic acid bacteria count was improved (P < 0.05) with increasing levels of WJW15. In conclusion, WJW15 isolated from kimchi supplementation in adult Beagle dog diet may have beneficial effects as a probiotic feed additive.

Effects of multi-enzyme on production performance, egg quality, nutrient digestibility, and excreta noxious gas emission of early phase Hy-line brown hens.

The purpose of this study was to investigate the effects of dietary supplementation of non-starch polysaccharide multi-enzyme (NME) in early laying phase of hens on production performance, egg quality, nutrient digestibility, and excreta noxious gas emission. In total, 432 Hy-line brown laying hens at 18 wk of age were used in a 10-wk feeding trail. Hens were randomly assigned to 1 of 3 treatments with 24 replication and 6 hens per replication (1 hen per cage). Dietary treatments were corn-soybean meal-DDGS-based diets supplemented with 0 (based diet, CON), 0.05% (NME1), and 0.1% (NME2) of NME. No significant (P > 0.05) response to increasing NME supplementation was observed for damaged egg rate shown throughout the experiment. Significant (P < 0.05) linear increase was observed for egg production at week 4, 6, and 8; moreover, egg production at week 8 also showed quadratic (P = 0.0344) increase. No significant effects were found on yolk color, eggshell strength, and eggshell thickness during the experiment (P > 0.05) with the increase in NME supplemental levels. Albumin height, haugh unit, and egg color values were linearly (P < 0.05) increased at week 2 and 6 following the increasing NME supplementation, respectively. Additionally, quadratic (P = 0.0013) effect was observed on egg weight at week 6 with the increasing level of NME. Moreover, apparent total tract digestibility of nitrogen and excreta ammonia emission was linearly (P < 0.05) affected increasing NME supplementation. In summary, inclusion of NME containing xylanase, ß-glucanase, galactosidase, and galactomannanase activities in corn-soybean meal-DDGS-based diets increased nitrogen digestibility, decreased excreta ammonia emission, and had no negative effects on production performance and egg quality parameters.

Dietary Supplementation of Mixed Yeast Culture Derived from Saccharomyces cerevisiae and Kluyveromyces maxianus: Effects on Growth Performance, Nutrient Digestibility, Meat Quality, Blood Parameters, and Gut Health in Broilers.

This study aimed to evaluate the effect of dietary supplementation of a mixed yeast culture (MYC; Saccharomyces cerevisiae YJM1592 and Kluyveromyces maxianus TB7258 in a 1:1 ratio) on growth performance, nutrient digestibility, meat quality, blood parameters, and gut health of broiler chickens. In total, 576 one-day-old male broilers (Ross 308) with an average initial bodyweight (BW) of 37±0.51 g were used in a 35-day experiment with a completely randomized design. The broilers were randomly assigned to 3 dietary treatments: CON, basal diet; TRT1, CON + 0.1% MYC; and TRT 2, CON + 0.2% MYC. From days 8 to 21, the feed conversion rate (FCR) was significantly decreased in broilers fed MYC-supplemented diets. From days 22 to 35, BW gain (BWG) significantly increased with increasing MYC concentration. Throughout the experiment, BWG increased (linear effect, P=0.002) and FCR decreased with increasing MYC in the diet. MYC supplementation increased the digestibility of dry matter (DM) in broilers in a dose-dependent manner. Relative organ weight of the bursa of Fabricius linearly increased in broilers fed MYC-supplemented diets. The white blood cell count showed linear and quadratic increases in broilers fed increasing concentrations of MYC. The population of Lactobacillus in the excreta linearly increased P=0.033, whereas that of Escherichia coli tended to linearly decrease (P=0.064) in the MYC groups. This study provides a basis for future research on MYC as a growth promoter in broilers.

Pharmacokinetic analysis of alpha and beta epimers of glycyrrhetinic acid in rat plasma: differences in singly and combined administrations.

An HPLC method for the determination of 18alpha-glycyrrhetinic acid and 18beta-glycyrrhetinic acid in rat plasma was established, which was used subsequently to determine the pharmacokinetic profiles of both epimers of glycyrrhetinic acid in rats. alpha-glycyrrhetinic acid, beta-glycyrrhetinic acid, and a mixture of alpha-glycyrrhetinic and beta-glycyrrhetinic acids were administered to rats via gastric infusion. Blood samples were collected at different time intervals and extracted by liquid-liquid extraction. Separation was achieved by using a Kromasil C18 column (150 mm x 4.6 mm, 5 microm) with the mobile phase composed of acetonitrile--4 mmol x L(-1) ammonium acetate solution (46 : 54, v/v) at a flow rate of 1.0 mL x min(-1), and the detection wavelength was set at 250 nm. The pharmacokinetic parameters were calculated using the software DAS 2.0. In a combined administration, the main pharmacokinetic parameters of beta-glycyrrhetinic acid are significantly different from that of alpha-glycyrrhetinic acid (P < 0.05), while no significant difference was obtained when administrated individually. Compared to the single administration, significant differences (P < 0.05) on the values of AUC(0-t) and AUC(0-infinity) of beta-glycyrrhetinic acid were observed when this chemical was administrated together with alpha-glycyrrhetinic acid. In contrast, the pharmacokinetic parameters of alpha-glycyrrhetinic acid were not affected even under the co-administration. Here, a sensitive, specific, rapid and reproducible HPLC method was developed for the pharmacokinetic studies of alpha-glycyrrhetinic acid and beta-glycyrrhetinic acid in rat plasma.