Low vitamin D during pregnancy is associated with infantile eczema by up-regulation of PI3K/AKT/mTOR signaling pathway and affecting FOXP3 expression: A bidirectional cohort study.

Vitamin D has received increasing attention because of its association with atopic disease development. Limited studies that have been done on the impact of maternal vitamin D levels during pregnancy on infantile eczema are still debatable. We wanted to discover the effect of maternal vitamin D on infantile eczema and explore whether regulatory T cells (Treg) play a role in this process. 219 pairs of mothers and children were enrolled. Maternal fasting venous blood was collected in pregnancy's second and third trimesters to determine vitamin D levels. Cord blood and placenta samples were collected during childbirth for detecting levels of genes, proteins and cytokines. Pediatricians followed up the prevalence of eczema in infants within 1 year. The reported rate of vitamin D deficiency and insufficiency was 35.6% and 28.3%. Lower maternal 25(OH)D3 levels were related to a higher risk of infantile eczema. Foxp3 gene expression is lower in cord blood of infants with eczema compared to infants without eczema. There was a positive correlation between maternal 25(OH)D3 levels and the expression of FOXP3 gene in cord blood. Compared to vitamin D sufficiency women, vitamin D deficiency women's placental FOXP3 protein expression was decreased and PI3K/AKT/mTOR protein was up-regulated. Our study demonstrates that low prenatal maternal vitamin D levels increased the risk of infantile eczema aged 0-1 year, which might be related to the downregulating of the FOXP3 gene expression in cord blood and decreased placental FOXP3 protein expression. Low placental FOXP3 protein was related with activating PI3K/AKT/mTOR signaling pathway.

Prenatal exposure to bisphenols, immune responses in cord blood and infantile eczema: A nested prospective cohort study in China.

Increasing evidence shows that human exposure to bisphenols can increase the risk of allergic disease, such as child asthma. However, the mechanism by which exposure to bisphenols causes allergic disease is unclear. In addition, the effects of exposure to bisphenols during pregnancy on infantile eczema have been poorly studied. The aim of our study was to investigate the effect of bisphenols (BPA, BPF and BPS) exposure during pregnancy on immune cells in cord blood, and on the occurrence of infantile eczema. 111 mother-child pairs with urine samples from pregnant women and cord blood were recruited from a birth cohort established in February 2019 in Shenyang, China. The levels of urinary bisphenols and Th1-, Th2-, Treg- and Th17-related genes, and cytokines in cord blood, as well as the incidence of infantile eczema at 6 and 12 months follow up were determined. Our results show that BPA, BPF and BPS were detected in 100%, 63.1% and 46.8% of the urine samples, respectively. The median concentration of urine specific gravity adjusted BPA (SG-BPA) was 7.46 ng/mL. High SG-BPA levels during pregnancy was independently associated with increased risk of infantile eczema (adjusted OR = 2.731, 95%CI: 1.064-7.012, P = 0.037). Higher levels of FOXP3 gene in cord blood had a significantly lower risk of developing eczema in infants (adjusted OR=0.430, 95%CI: 0.190-0.972, P = 0.042). However, BPS and BPF levels were not associated with infantile eczema. FOXP3 gene levels in cord blood mediated the relationship between SG-BPA levels during pregnancy and infantile eczema (indirect effect: ß = 0.350 [CI:0.011,1.077]). Our findings indicate that high levels of BPA exposure during pregnancy increase the risk of infantile eczema, which may be associated with down-regulation of FOXP3 gene expression in cord blood.

Association of prenatal factors and cord blood lead levels in China: A nested cohort cross-sectional study.

BACKGROUND: Lead exposure all over the world has gradually declined. As fetuses are more prone to lead exposure, even to low levels of lead exposure, it is important to monitor blood lead levels (BLLs) in pregnancy. METHODS: We obtained data on BLLs in the third trimester of pregnancy from medical records and measured cord BLLs obtained from 121 mother-child pairs in Shenyang, China from September 2019 to February 2020. We also estimated relationships between socio-demographic, lifestyle and dietary factors during pregnancy as well as cord BLLs to identify the source of lead exposure during pregnancy. BLLs was estimated by atomic absorption spectrometry through graphite furnace ionization techniques. The data which obtained by questionnaires during pregnancy included maternal sociodemographic, lifestyle, dietary factors. We have established three multivariate logistic regression models in which the dichotomous BLLs was used as the dependent variable (cord BLLs ≥20 µg/L vs <20 µg/L). RESULTS: The median and geometric mean of cord BLLs were 22.90 µg/L, 21.88 µg/L and BLLs in the third trimester of pregnancy were 25.29 µg/L, 24.66 µg/L, respectively. BLLs showed significant correlations between cord and the third trimester of pregnancy (r = 0.277, P = 0.012). Pregnant women who had not been exposed to passive smoking had lower OR (95 %) [0.43(0.19-0.94)] for cord BLLs ≥20 µg/L than pregnant women who had. Intake of docosahexaenoic acid (DHA) during third trimester of pregnancy presented an OR (95 %) [0.23(0.08-0.61)] for cord BLLs ≥20 µg/L. Consuming more whole grains (>3 times/week) and beverage (≥1 times/week) showed an OR (95%CI) for cord BLLs ≥20 µg/L of 0.09(0.02-0.53) and 0.19(0.06-0.69), respectively. CONCLUSION: This study showed the cord BLLs of Chinese are still higher than most developed countries. Passive smoking is a risk factor for cord BLLs ≥20 µg/L and supplement of DHA, whole grains and beverage consumption during pregnancy may act as a beneficial factor against having cord BLLs ≥20 µg/L.

Synthetic antimicrobial agents inhibit aflatoxin production.

Antimicrobial peptides (AMPs) are biologically active molecules that can eradicate bacteria by destroying the bacterial membrane structure, causing the bacteria to rupture. However, little is known about the extent and effect of AMPs on filamentous fungi. In this study, we synthesized small molecular polypeptides by an inexpensive heat conjugation approach and examined their effects on the growth of Aspergillus flavus and its secondary metabolism. The antimicrobial agents significantly inhibited aflatoxin production, conidiation, and sclerotia formation in A. flavus. Furthermore, we found that the expression of aflatoxin structural genes was significantly inhibited, and the intracellular reactive oxygen species (ROS) level was reduced. Additionally, the antimicrobial agents can change membrane permeability. Overall, our results demonstrated that antimicrobial agents, safe to mammalian cells, have an obvious impact on aflatoxin production, which indicated that antimicrobial agents may be adopted as a new generation of potential agents for controlling aflatoxin contamination.

The Association Between Environmental Lead Exposure and Recurrent Respiratory Infections in Children Aged 3-7 Years in Shenyang, China.

OBJECTIVE: To investigate the lead exposure levels, and the effect of blood lead level (BLL) on recurrent respiratory infections in children aged 3-7 years in Shenyang. METHODS: A case-control study including 78 children with recurrent respiratory infections and 141 controls was performed. Venous blood was obtained for BLL, and a questionnaire was completed. RESULTS: The BLL was significantly higher in children with recurrent respiratory infections than that in the control group [Median (IQR): 2.56 (1.29-6.19) vs 1.99 (0.90-5.92) µg/dL, P=0.029]. Children with BLL ≥1.95 µg/dL were more likely to be suffering from recurrent respiratory infections (OR=2.328, 95%CI=1.228-4.413) than those with BLL <1.95 µg/dL. CONCLUSIONS: High lead level can increase the risk of respiratory infections in preschool children.

Combined effects of obesity and di-(2-ethylhexyl) phthalate on testosterone levels and kisspeptin/GPR54 expression in hypothalamus and testes of male mice.

BACKGROUND: This study evaluated whether obese male mice exposed to di-(2-ethylhexyl) phthalate (DEHP) showed synergistic effects on testosterone levels and the potential underlying mechanism. METHODS: Forty-eight male mice were assigned to six groups for 12-week treatments as follows: normal, DEHP100, diet-induced obesity (DIO), DIO + DEHP30, DIO + DEHP100, and DIO + DEHP300. Serum hormone levels, including testosterone (T), luteinizing hormone (LH), and leptin, were detected by ELISA. The levels of Ob-R, kisspeptin, and GPR54 protein expression in hypothalamus and testicular tissues were measured by western blot. RESULTS: There were significantly lower levels of serum T and LH, higher levels of serum leptin and Ob-R, and kisspeptin and GPR54 protein expression were reduced in hypothalamus and testicular tissues in the DIO and DEHP groups compared with controls. Moreover, serum T and leptin levels were more severe in the combined DIO and DEHP exposure group than in the single exposure groups. Serum LH levels and GPR54 expression in the testis were significantly decreased in DIO + DEHP300 mice compared with DIO mice (p < 0.05). CONCLUSION: Obesity- and DEHP-only exposure had adverse effects on testosterone levels in mice, which may be due to high leptin levels and decreased Ob-R, kisspeptin, and GPR54 expression. Obesity combined with DEHP exposure had an additive adverse effect on testosterone levels in mice. One of the potential mechanisms is higher leptin levels and decreased GPR54 expression in the testes.

Non-alcoholic Fatty Liver Disease Induced by Perinatal Exposure to Bisphenol a Is Associated With Activated mTOR and TLR4/NF-κB Signaling Pathways in Offspring Rats.

Accumulating evidence suggests a role of bisphenol A (BPA) in non-alcoholic fatty liver disease (NAFLD), and its mechanism may be related to the up-regulation of lipogenic genes, but the mechanism of BPA induced lipogenic gene expression remains unknown. The aim of this study was to investigate the effects of perinatal exposure to BPA on NAFLD and its mechanisms. Pregnant Sprague-Dawley rats had access to drinking water containing 1 or 10 µg/ml BPA from gestational day 6 to post-natal day 21. For 5 weeks after weaning, offspring drank normal water without BPA. Body weight, lipid profile and the expression of genes or proteins involved in mTOR mediated lipid metabolism and autophagy, as well as inflammatory response were investigated in the 8-wk-old offspring of different genders. The results showed that body weight was increased only in females, however, males, and females from dams treated with BPA had significantly excess visceral adipose tissue, which was consistent with adipocyte hypertrophy. Elevated TG levels and up-regulation of lipogenic genes or proteins in liver, such as sterol regulatory element binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS) were consistent with increased liver lipid droplets in offspring exposed to BPA. Compared with controls, the protein levels of InsR, p-IRS-1, IRS-1, TSC1, and TSC2 were decreased, p-PI3K, p-Akt (S473), p-Akt (T308), p-mTOR, and mTOR were increased, and the impaired autophagic degradation was evidenced by increased protein levels of p62, although the levels of p-ULK1, Beclin1, and LC3B proteins were increased in liver of BPA-exposed offspring. The levels of TLR4 and NF-κB proteins were also significantly increased, and ERα protein was significantly decreased in BPA-exposed offspring. Our findings indicate that perinatal exposure to BPA causes the development of NAFLD in both female and male offspring, which is associated with up-regulation of lipogenic genes, dysregulated autophagy and activated inflammatory response involving the PI3K/Akt/mTOR and TLR4/NF-κB pathways.

Effect of Perinatal Bisphenol A Exposure on Serum Lipids and Lipid Enzymes in Offspring Rats of Different Sex.

Rats were exposed to 1 or 10 µg/mL bisphenol A (BPA) in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day (PND) 50. Perinatal exposure to BPA resulted in significantly increased body weight, visceral adipose tissue, abnormal serum lipids, and lower adiponectin (ADP) levels in both female and male offspring rats. Liver adipose triglyceride lipase (Atgl) mRNA levels and ADP protein in visceral adipose tissue were significantly decreased in BPA-exposed offspring rats. In both female or male offspring rats, obesity and dyslipidemia induced by perinatal exposure to BPA were associated with down regulation of Atgl mRNA in liver and ADP protein in visceral adipose tissue.

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.

[Effects of fluoride on proliferation and differentiation of rat osteoblasts in vitro and the antagonistic action of vitamin C].

OBJECTIVE: To study the effects of fluoride on the proliferation and differentiation of osteoblasts in sucking rats and the antagonism of vitamin Cin vitro. METHODS: The enzyme digesting method was used to isolate the rat osteoblasts; the proliferative response was determined by the percents of reduced alamarBlue; the activity of alkaline phosphatase (ALP) was measured by ELISA method. RESULTS: The proliferation of sucking rat osteoblasts was increased at 0.10 - 1.00 mmol/L of NaF, whereas inhibited at >or= 2.00 mmol/L. ALP activity was increased at 0.01 - 0.05 mmol/L of NaF, and decreased at >or= 0.10 mmol/L. The inhibition on proliferation and differentiation at 2 mmol/L NaF was antagonized by vitamin C. CONCLUSION: Fluoride had a two-phase effect on osteoblasts, vitamin C could antagonize the inhibitory effect of higher concentration of fluoride on proliferation and differentiation of osteoblasts.