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Background: T-cell exhaustion (Tex) can be beneficial in autoimmune diseases, but its role in Graves' disease (GD), an autoimmune disorder of the thyroid, remains unknown. This study investigated Tex-related gene expression in GD patients to discern the potential contributions of these genes to GD pathogenesis and immune regulation. Methods: Through gene landscape analysis, a protein-protein interaction network of 40 Tex-related genes was constructed. mRNA expression levels were compared between GD patients and healthy control (HCs). Unsupervised clustering categorized GD cases into subtypes, revealing distinctions in gene expression, immune cell infiltration, and immune responses. Weighted gene co-expression network analysis and differential gene expression profiling identified potential therapeutic targets. RT-qPCR validation of candidate gene expression was performed using blood samples from 112 GD patients. Correlations between Tex-related gene expression and clinical indicators were analyzed. Results: Extensive Tex-related gene interactions were observed, with six genes displaying aberrant expression in GD patients. This was associated with atypical immune cell infiltration and regulation. Cluster analysis delineated two GD subtypes, revealing notable variations in gene expression and immune responses. Screening efforts identified diverse drug candidates for GD treatment. The Tex-related gene CBL was identified for further validation and showed reduced mRNA expression in GD patients, especially in cases of relapse. CBL mRNA expression was significantly lower in patients with moderate-to-severe thyroid enlargement than in those without such enlargement. Additionally, CBL mRNA expression was negatively correlated with the disease-specific indicator thyrotropin receptor antibodies. Conclusion: Tex-related genes modulate GD pathogenesis, and their grouping aids subtype differentiation and exploration of therapeutic targets. CBL represents a potential marker for GD recurrence.

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Hyperglycemia plays crucial roles in vascular disease development, including macrovascular and microvascular diseases from diabetes mellitus (DM). Our previous study demonstrated that Ruellia tuberosa L. (RTL) aqueous and ethanol extracts alleviate hyperglycemia and inhibit insulin resistance in diabetic rats. This study investigated the protective effect of RTL ethanol extract against aorta dysfunction in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 DM (T2DM) rats. Results showed that RTL ethanol extract (100 and 400 mg/kg BW/day) ameliorated serum lipid profiles, including triglyceride, free fatty acid, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. It also significantly reduced the level of serum cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 in T2DM rats. Additionally, RTL extract decreased endothelin-1 and endothelial nitric oxide contents, reduced the level of cell adhesion factors, including monocyte chemoattractant protein-1 and cell adhesion factor vascular cell adhesion molecule-1, while decreasing content of damage factors, namely tissue factor and von Willebrand factor in aortic tissues of diabetic rats. Equally noteworthy is that RTL extract enhanced the activity of aorta antioxidative enzymes, including superoxidase dismutase and catalase in diabetic rats, suggesting that RTL ethanol extract may ameliorate aorta dysfunction via enhancing aortic antioxidative enzyme activity, which subsequently suppresses aorta endothelial damage-associated factors in HFD with STZ-induced T2DM rats.

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Ruellia tuberosa L. (RTL) exhibits a wide range of phytochemical activities, for example, on treatment of diabetes mellitus (DM), in Orient. There is, however, few study regarding the effect of RTL on glycemic-related homeostasis in type 2 DM (T2DM). We investigated the effect of RTL aqueous and ethanolic extracts on hypoglycemia in high-fat diet (HFD)-fed plus streptozotocin (STZ)-induced T2DM rats, and examined the effect of RTL on glucose uptake in tumor necrosis factor-α-induced insulin-resistant mouse C2C12 myoblasts, a mouse skeletal muscle cell line. The administration of 100 or 400 mg kg BW-1 day-1 of RTL aqueous or ethanolic extracts once a day for 4 weeks significantly ameliorated hyperglycemia, hyperinsulinemia, and the insulin resistance (IR) index in diabetic rats. RTL either aqueous or ethanolic extract at a concentration of 25-800 µg/ml significantly improved glucose uptake in insulin-resistant mouse C2C12 myoblasts, indicating inhibiting the IR in skeletal muscles. These evidences suggest that RTL ameliorates hyperglycemia in HFD/STZ-induced T2DM rats may be attributed to the alleviation of IR in skeletal muscles.

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BACKGROUND: Marinating meat with alcohol, such as wine and beer, is a common culinary practice in cultures worldwide. In this study we use a model marination solution comprising 0.2  mol L-1 glucose-0.2  mol L-1 glycine buffered to pH 4.3 containing either 0 or 50% ethanol and mimicked the cooking process by heating for 12 h. Antioxidative and antimutagenic characteristics of Maillard reaction products (MRPs) were investigated. Reducing power, antioxidant activity (ferrous ion chelating ability), and free radical neutralization ability generated from 1,1-diphenyl-2-pichrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) were determined. Ames testing was performed. RESULTS: Results indicate that MRPs from aqueous and alcoholic solution exhibit four antioxidative assays in a dose-dependent manner from 0.16 to 10.00 mg mL-1 . However, MRPs from the alcoholic model were superior. In Ames testing, MRPs from both models are neither toxic nor mutagenic at the test concentrations of 0.63-10.00 mg/plate. However, MRPs from the alcoholic model exhibited a higher inhibitory effect on the direct-acting mutagen 4-nitroquinoline-N-oxide compared with the aqueous model. This result is consistent with the observation that MRPs with higher antioxidative capacity exhibit superior antimutagenic activity, suggesting that there are more different products in the alcoholic model. CONCLUSION: Our results add to the current knowledge about the antioxidative and antimutagenic properties of MRPs arising when food is cooked in the presence of ethanol. © 2018 Society of Chemical Industry.

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OBJECTIVE: A relationship between iodine intake and the effectiveness of antithyroid drug (ATD) therapy for Graves' disease (GD) has been suggested, and strict restriction of iodine intake has been tried in the treatment of GD in some studies. However, it is unclear whether dietary iodine supplementation improves the prognosis of ATD therapy for GD. This study aimed to clarify whether optimal iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction. METHODS: This was a prospective randomized trial of newly diagnosed patients with GD. Patients with newly diagnosed GD were recruited. After ATD therapy and strict dietary iodine restriction for 1 month, patients (n = 459) were randomly assigned to iodine-supplemented and iodine-restricted groups. After exclusion, 405 patients finally completed the study. The iodine-supplemented group included 203 patients (61 males and 142 females) with an average age of 32.2 ± 10.5 years (17-65 years), and the iodine-restricted group included 202 patients (61 males and 141 females) with an average age of 31.9 ± 11.8 years (16-64 years). Patients in the iodine-supplemented group were given about 10 grams of iodized salt every day, while the iodine-restricted group received noniodized salt with low-iodine or noniodine diet. The dietary iodine intervention lasted for 24 months. Urinary iodine concentration (UIC), thyrotropin receptor antibody (TRAb), free T3 (FT3), free T4 (FT4) and thyrotropin (TSH) of 2 groups were measured every 3 months. The recurrence rates within 12 months after withdrawal of ATD were evaluated. RESULTS: UIC in the iodine-supplemented group was within the recommended range for optimal iodine intake (135-162 µg/L) and was significantly higher than that in iodine-restricted group (30-58 µg/L). Within 12 months of withdrawal of ATD, the total recurrence rate in the iodine-supplemented group was 35.5%, significantly lower than in the iodine-restricted group, which was 45.5%. CONCLUSION: Optimal dietary iodine supplementation during antithyroid drug therapy for GD is associated with lower recurrence rates than iodine restriction, and therefore, diet control with strict iodine restriction might be an adverse factor in the management of GD.

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BACKGROUND: Previous studies suggest that visceral fat is associated with type 2 diabetes (T2D) independent of body mass index (BMI). However, epidemiological data about the relationship between visceral fat and T2D are rare in Chinese. The aim of the present study was to investigate whether visceral fat area (VFA) is associated with T2D beyond and above BMI in the Chinese population. METHODS: The present community-based cross-sectional study was conducted in 2013 on 4126 individuals (2545 women, 1581 men) aged ≥ 40 years, with T2D diagnosed according to 1999 World Health Organization criteria. The VFA was measured by a fat area analyzer using bioelectrical impedance analysis. RESULTS: Participants were categorized into normal weight and overweight/obese groups according to BMI. Within each group, compared with women with below-median VFA, women with above-median VFA had a significantly increased risk of diabetes (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.31-2.69 in the normal weight group; OR 2.10, 95% CI 1.54-2.85 in the overweight/obese group), whereas among men the corresponding associations were not significant in either group. Among women, after multivariable adjustment including BMI, each one standard deviation increase in VFA was significantly associated with a 45% higher risk of having T2D (OR 1.45, 95% CI 1.26-1.67), whereas among men BMI, not VFA, was independently associated with T2D (OR 1.18, 95% CI 1.02-1.37). CONCLUSIONS: Visceral fat was independently associated with T2D in women regardless of obesity status, whereas in men BMI may have a more important effect on T2D than visceral fat.

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