Decreased Treg cells induced by bisphenol A is associated with up-regulation of PI3K/Akt/mTOR signaling pathway and Foxp3 DNA methylation in spleen of adolescent mice.

The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 µg mL-1) group, OVA + BPA (0.2 µg mL-1) group, and OVA + BPA (0.4 µg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.

Increased levels of IL-17 and autoantibodies following Bisphenol A exposure were associated with activation of PI3K/AKT/mTOR pathway and abnormal autophagy in MRL/lpr mice.

Bisphenol A (BPA) is a common environmental endocrine disruptor which mimic the effect of estrogen. The immunotoxicity of BPA has attracted widespread attention in recent years. However, the effects and mechanism of BPA on autoimmune disease were rarely reported. Systemic lupus erythematosus (SLE) is a typical autoimmune disease, and its etiology and mechanism are complex and unclear. Currently, inflammation and the production of autoantibodies are considered to be important pathological mechanisms of SLE, and estrogen contributes to the occurrence and development of SLE. Therefore, in order to explore whether BPA exposure can affect the development of SLE and its possible mechanism, we used MRL/lpr (lupus-prone mice) and C57/BL6 female mice exposed to 0.1 and 0.2 µg/mL BPA for 6 weeks. We discovered that BPA exposure increased the concentration of serum anti-dsDNA antibody and IL-17, and the level of RORγt protein (the transcription factor of Th17 cells). Moreover, there were higher expression of p-PI3K, p-AKT, p-mTOR, ULK, Rubicon, P62, Becline1 and LC3 protein in spleen tissue of BPA exposed MRL/lpr mice compared with the control. However, there were no significant changes in the expression of IL-17, RORγt or mTOR in C57 mice exposed to BPA at the same dose. Our study implied that BPA exposure induced the development of SLE, which might be related to the up-regulation of PI3K/AKT/mTOR signaling pathway and abnormal autophagy. Our study indicated that lupus mice were more susceptible to BPA, and provided a new insight into the mechanism by which BPA exacerbated SLE. Therefore, our study suggested that autoimmune patients and susceptible population should be considered when setting thresholds for environmental BPA exposure.

Exacerbating lupus nephritis following BPA exposure is associated with abnormal autophagy in MRL/lpr mice.

For the development of Lupus nephritis, environmental factors are reasoned to be one of the risk factors. In recent years, the role of bisphenol A (BPA) in kidney injury has attracted wide attention. In this study, we explored the nephrotoxicity and its possible mechanism of BPA exposure to lupus-prone MRL/lpr mice. Orally exposure of BPA increased serum anti-dsDNA level and urinary protein, and aggravated renal pathological injury in MRL/lpr mice. BPA increased the expression of NF-κB protein and activated the inflammatory response in both MRL/lpr and C57 mice. Unlike C57 mice, BPA exposure partially activated autophagy associated proteins, but the autophagy signaling pathway lacked the regulation of Becline1 and LC3-associated phagocytosis deficiency, and decreased Nrf2 protein expression in renal tissue of MRL/lpr mice. Therefore, exacerbating lupus nephritis induced by BPA exposure was associated with the activation of inflammation, abnormal autophagy and decreased antioxidant ability.

The imbalance of Treg/Th17 cells induced by perinatal bisphenol A exposure is associated with activation of the PI3K/Akt/mTOR signaling pathway in male offspring mice.

Bisphenol A (BPA) can inhibit the differentiation and function of regulatory T cells (Treg), and affect the balance of helper T cell (Th) 1/Th2, therefore, the immunotoxicity of BPA has attracted widespread attention in recent years, but its mechanism is not clear. The main aim of this study was to explore the regulatory mechanism of the PI3K/Akt/mTOR signaling pathway in the context of perinatal exposure to BPA-induced Treg/Th17 imbalance in male offspring mice through a combination of in vivo and in vitro methods. Our results showed that perinatal exposure to BPA could increase the number of Th17 cells while decreasing Treg cell numbers, which was consistent with the expression levels of up-regulation of RORγt protein and a down-regulation FOXP3 protein in the splenocytes of the male offspring mice. BPA could activate the PI3K/Akt/mTOR signaling pathway and increase the inflammatory response, as evidenced by higher serum IL-17 and TNF-α levels by inducing the activation of the AhR and TLR4/NF-κB signaling pathways. Moreover, our results also supported the hypothesis whereby the Treg/Th17 imbalance, induced by perinatal exposure to BPA, was associated with the activation of PI3K/Akt/mTOR signaling in vitro-cultured peripheral blood mononuclear cells by using rapamycin as an inhibitor of mTOR.

Trends in obesity, overweight, and malnutrition among children and adolescents in Shenyang, China in 2010 and 2014: a multiple cross-sectional study.

BACKGROUND: The prevalence, characteristics, and trends in obesity, overweight, and malnutrition among children and adolescents in 2010 and 2014 in Shenyang, China was described. METHODS: This was a multiple cross-sectional study using data from the 2010 and 2014 National Survey on Students' Constitution and Health. A total of 31,031 children and adolescents were included in this survey. Differences in the percentages of obesity, overweight, and malnutrition by age, gender, and living region in 2010 and 2014 were compared using the χ2 test. Stepwise logistic regression was performed to select potential covariates for the dependent variable (overweight, obesity, or malnutrition). RESULTS: The prevalence of obesity and overweight in 2010 was 8.99% and 13.72%, respectively, and 12.64% and 14.06% in 2014, respectively. The prevalence of malnutrition was 10.68% and 10.69% in 2010, and 2014, respectively. In 2010 and 2014, boys and girls 7-11 years of age had higher rates of obesity than other age groups (P < 0.01). The prevalence of obesity and overweight was significantly higher in the urban residents compared to the rural residents, and was also significantly higher in boys than girls (P < 0.01); however, the prevalence of malnutrition was significantly lower in boys than girls (P < 0.01). Compared to 2010, the prevalence of obesity in 2014 increased significantly in boys and girls, and urban and rural residents (P < 0.05), but the prevalence of malnutrition did not change. The prevalence of obesity, overweight, and malnutrition was associated with gender, age, and living region by univariate logistic regressions. CONCLUSION: The prevalence of obesity and overweight has continuously risen since 2010, and there is a low-age trend of obesity and overweight among children and adolescents in Shenyang, China. The increasing rate of obesity and overweight was faster in rural than urban areas. Malnutrition did not significantly decrease during the 4-year period from 2010-2014.

MiR-410 Down-Regulates the Expression of Interleukin-10 by Targeting STAT3 in the Pathogenesis of Systemic Lupus Erythematosus.

BACKGROUND/AIMS: Systemic lupus erythematosus (SLE) is a heterogeneous chronic inflammatory autoimmune disorder, in the pathogenesis of which miRNAs play a versatile function. The purpose of this study was to investigate the effect of miRNA-410 on the pathogenesis of SLE in T cells of SLE patients. METHODS: Real-time PCR was used to test the mRNA levels of miRNA-410 in SLE patients and healthy controls. ELISA analysis was performed to examine the production levels of IL-10. Luciferase Assay was used to confirm the targeting effect of miRNA-410 on 3'UTR of STAT3 mRNA. RESULTS: We found that the expression level of miR-410 in T cells of SLE patients was decreased comparing to that in healthy controls, whereas overexpression of miR-410 significantly reduced the expression levels of IL-10. Furthermore, miR-410 suppresses the transcription activity of STAT3 by binding directly to the 3 'UTR of STAT3 mRNA. Moreover, silence of STAT3 down regulated IL-10 expression in CD3+ T cells. CONCLUSION: Our results demonstrate that miR-410 is the key regulatory factor in the pathogenesis of SLE by regulating the expression of IL-10 through targeting STAT3. These data suggest a novel function of miR-410 and bring new insight into understanding the complex mechanisms involved in SLE.

Effect of (R)-α-lipoic acid supplementation on serum lipids and antioxidative ability in patients with age-related macular degeneration.

BACKGROUND/AIMS: Supplementation with antioxidants is of special interest in preventing or delaying the development and progression of age-related macular degeneration (AMD). This investigation aimed to assess the effect of α- lipoic acid (LA) on serum lipids, serum malondialdehyde (MDA) and superoxide dismutase (SOD) in patients with AMD. METHODS: A total of 62 patients (50-75 years old) with early and intermediate dry form of AMD were randomly assigned to two groups, i.e. LA administration (n = 32) and placebo (n = 30). The levels of serum lipids and MDA and SOD activity were measured before and after LA and placebo intervention. RESULTS: Compared with the parameters at baseline, serum total cholesterol (CHO), triglyceride and high- and low-density lipoprotein CHO (HDL and LDL) levels were not significantly different after LA and placebo intervention. There was a slight but statistically nonsignificant decrease in serum MDA levels and a statistically significant increase in serum SOD activity after LA intervention. There were no statistically significant differences in serum MDA levels or SOD activity after placebo intervention. CONCLUSION: The apparent increase in SOD activity caused by LA supplementation indicates that LA may have a possible preventive effect in the development of AMD through an antioxidant mechanism.

Serum superoxide dismutase and malondialdehyde levels in a group of Chinese patients with age-related macular degeneration.

BACKGROUND AND AIMS: The aim of this study was to investigate superoxide dismutase (SOD) activity together with malondialdehyde (MDA) levels in a group of Chinese patients with age-related macular degeneration (AMD). METHODS: Serum SOD activity and MDA levels were analysed in 56 AMD patients with subtypes (early dry, geographic atrophy, and wet) and 34 healthy controls matched with age and sex. RESULTS: Serum MDA levels were significantly higher in AMD (3.68 ± 1.06 nmol/mL) than in controls (2.83 ± 0.43 nmol/mL; p=0.000), and was significantly higher in wet AMD (3.79 ± 0.79 nmol/mL) than in early dry AMD (3.26 ± 0.99 nmol/mL; p=0.038). Serum SOD activity was significantly higher in AMD (87.12 ± 13.22 U/mL) than in controls (79.91 ± 11.80 U/mL; p=0.012), and slightly higher in wet AMD (89.52 ± 16.25 U/mL) than in GA (83.62 ± 9.75 U/mL; p=0.275) and early dry AMD (81.64 ± 18.90 U/mL; p=0.093). There was a positive correlation between serum MDA levels and SOD activities in AMD patients and controls (r=0.320, p=0.002). CONCLUSIONS: The observed increase in SOD activity in our study may be related to increased MDA levels, as a compensatory regulation in response to oxidative stress in AMD patients. The present data also demonstrate that oxido-reduction disturbance may be hypothesized in the pathogenesis of AMD.