High Levels of BPA and BPF Exposure during Pregnancy Are Associated with Lower Birth Weight in Shenyang in Northeast China.

Animal studies indicate that bisphenol A (BPA) has obesogenic effects. Recent experiments reported similar endocrine-disrupting effects of bisphenol F (BPF) and bisphenol S (BPS), which are substitutes of BPA. The aim of this study was to investigate the exposure levels of these bisphenols in pregnant women and their effects on the physical development of infants aged 0-12 months. This study recruited pregnant women who gave birth at a hospital between February 2019 and September 2020. Urine samples from these pregnant women in the third trimester of pregnancy were detected by using ultrahigh-performance liquid chromatography-triple quadruple mass spectrometry. Follow-ups at 6 and 12 months of age were conducted by telephone by pediatricians using a structured questionnaire. Multiple linear regressions were used to determine the associations between bisphenol concentrations and infant weight. A total of 113 mother-child pairs had complete questionnaires and urine samples as well as data on newborns aged 6 months and 12 months. The detection rates of urinary BPA, BPF, and BPS in pregnant women were 100, 62.83, and 46.02%, respectively. Their median levels are 5.84, 0.54, and 0.07 µg/L, respectively. Increased urinary BPA and BPF concentrations during pregnancy were significantly associated with lower birth weight (standardized regression coefficients [ß] = -0.081 kg, 95% confidence interval [CI]: -0.134 to -0.027; ß = -0.049 kg, 95% CI: -0.097 to -0.001). In addition, urinary BPA and BPF concentrations during pregnancy were positively associated with weight growth rate from 0 to 6 months (ß = 0.035 kg/mouth, 95% CI: 0.00-0.064; ß = 0.028 kg/mouth, 95% CI: 0.006-0.050), especially in female infants (ß = 0.054 kg/mouth, 95% CI: 0.015-0.093; ß = 0.035 kg/mouth, 95% CI: 0.005-0.065). Therefore, maternal BPA and BPF levels during pregnancy were negatively correlated with birth weight and positively correlated with the growth rate of infant weight at 0-6 months of age, especially in female infants.

Urinary concentrations of bisphenol A and its alternatives: Potential predictors of and associations with antral follicle count among women from an infertility clinic in Northern China.

BACKGROUND: Experimental studies have suggested exposure to bisphenol A (BPA) and its alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), may exert adverse effects on ovarian reserve, but human evidence is limited. Moreover, the potential predictors of exposure to bisphenols among women seeking infertility treatment have not been reported. OBJECTIVE: To explore whether individual or mixture of BPA, BPF, and BPS were related to antral follicle count (AFC), and further identify the predictors of exposure to bisphenols among women seeking assisted reproductive treatment. METHODS: A total of 111 women from a reproductive center in Shenyang, China were enrolled in this study from September 2020 to February 2021. The concentrations of urinary BPA, BPF, and BPS were measured using ultra-high-performance liquid chromatography-triple quadruple mass spectrometry (UHPLC-MS/MS). AFC was measured by two infertility physicians through transvaginal ultrasonography on the 2-5 days of a natural cycle. Demographic characteristics, dietary habits, and lifestyles were obtained by questionnaires. The associations between individual and mixture of urinary bisphenols concentrations (BPA, BPF, and BPS) and AFC were assessed by the Poisson regression models and the quantile-based g-computation (QGC) model, respectively. The potential predictors of exposure to bisphenols were identified by the multivariate linear regression models. RESULTS: After adjusting for confounders, elevated urinary concentrations of BPA, BPF and BPS were associated with reduced AFC (ß = -0.016; 95%CI: -0.025, -0.006 in BPA; ß = -0.017; 95%CI: -0.029, -0.004 in BPF; ß = -0.128; 95%CI: -0.197, -0.060 in BPS). A quantile increase in the bisphenols mixture was negatively associated with AFC (ß = -0.101; 95%CI: -0.173, -0.030). Intake of fried food had higher urinary concentrations of BPF, BPS, and total bisphenols (∑BPs) than women who did not eat, and age was related to increased urinary BPF concentrations. CONCLUSION: Our findings indicated that exposure to individual BPA, BPF, BPS and bisphenol mixtures were associated with impaired ovarian reserve. Furthermore, the intake of fried food, as identified in this study, could serve as an important bisphenols exposure route for reproductive-aged women.

Maternal dietary patterns during pregnancy and the risk of infantile eczema during the first year of life: a cohort study in northeast China.

BACKGROUND: There are few studies on the relationship between diet during pregnancy and infantile eczema and the conclusions are inconsistent. The aim of the present study was to explore the impact of dietary patterns during pregnancy on infantile eczema. METHODS: A total of 495 mother-child pairs from a prospective cohort in Shenyang, China was recruited. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered food frequency questionnaire. The data of infantile eczema was assessed using a structured questionnaire. Factor analysis to derive dietary patterns. The relationship between the dietary pattern and infantile eczema was examined by the logistic regression analysis. RESULTS: The cumulative incidence of eczema in 6 months and 12 months in northeast China was 45.7% and 57.8%, respectively. Three dietary patterns were identified. There was a tendency for an expose-response relationship between the maternal high-protein dietary pattern during pregnancy and the risk of infantile eczema within 12 months (P for trend = 0.023): the adjusted odds ratio (95% confidence interval) in the Q1, Q2, Q3, Q4 were 1.00 (reference), 1.63 (0.96-2.76), 1.81 (1.06-3.06), and 1.87 (1.09-3.20), respectively. No association between Western and plant-based patterns during pregnancy and infantile eczema within 12 months was found. Infantile eczema within 6 months was not associated with any of the three dietary patterns. CONCLUSION: The maternal high-protein pattern during pregnancy may be a risk factor for infantile eczema during the first year of life.

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.

Urinary bisphenol A and S are associated with diminished ovarian reserve in women from an infertility clinic in Northern China.

Bisphenol A (BPA) has been demonstrated to cause ovarian toxicity including disruption of steroidogenesis and inhibition of follicle growth. Still, human evidence is lacking on its analogs such as bisphenol F (BPF) and bisphenol S (BPS). In this study, we aimed to investigate the associations between exposure to BPA, BPF, and BPS with ovarian reserve in women of childbearing age. We recruited 111 women from an infertility clinic in Shenyang, North China between September 2020 and February 2021. Anti-müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) were measured as indicators of ovarian reserve. Urinary BPA, BPF, and BPS concentrations were quantified by ultra-high-performance liquid chromatography-triple quadruple mass spectrometry (UHPLC-MS/MS). Linear and logistic regression models were applied to assess the associations between urinary BPA, BPF, and BPS levels and indicators of ovarian reserve and DOR, respectively. Restricted cubic spline (RCS) models were further utilized to explore potential non-linear associations. Our results showed that urinary BPS concentrations were negatively associated with AMH (ß = - 0.287, 95 %CI: - 0.505, - 0.070, P = 0.010) and this inverse relationship was further confirmed in the RCS model. In addition, higher levels of BPA and BPS exposure were associated with increased DOR risk (BPA: OR = 7.112, 95 %CI: 1.247, 40.588, P = 0.027; BPS: OR = 6.851, 95 %CI: 1.241, 37.818, P = 0.027). No significant associations of BPF exposure with ovarian reserve. Our findings implied that higher BPA and BPS exposure may be related to decreased ovarian reserve.

Effects of mammalian target of rapamycin and aryl hydrocarbon receptor-mediating autophagy signaling on the balance of Th17/Treg cells during perinatal bisphenol A exposure in female offspring mice.

Bisphenol A (BPA)'s immunotoxic properties have received increasing interest, which can lead to immune dysfunction and related disease development. However, the mechanism is not completely clear. A growing body of evidence suggests that autophagy has important roles in innate immunity, inflammatory response, and adaptive immunity. This study aimed to investigate the possible mechanisms of mammalian target of rapamycin (mTOR), aryl hydrocarbon receptor (AhR), and autophagy in Treg/Th17 imbalance induced by perinatal BPA exposure. Our results showed that the number of Th17 cells in the spleen of offspring female mice significantly increased, while the number of Treg cells decreased significantly, which was consistent with the expression levels of up-regulation of RORγt protein and a down-regulation Foxp3 protein. The levels of mTOR, p-mTOR, P62, and AhR protein expression increased, and LC3 protein decreased in spleen. However, in the thymus, we found that RORγt and Foxp3 proteins changed most significantly in the low-dose BPA group, and the same as p-mTOR and P62 protein levels. We conjectured that the potential mechanism of the imbalance of Th17/Treg upon perinatal exposure to BPA was probably associated with autophagy dysfunction. Proper autophagy plays an important role in maintaining the homeostasis of the thymic and spleen immune system.

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.

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.

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.

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.

Inactivation effects and mechanism of ohmic heating on Bacillus cereus.

The inactivation effects and mechanism of ohmic heating (OH) on Bacillus cereus ATCC 11778 were investigated in this study, conventional heating (CH) was also carried out and served as control. All OH treatments (10 V/cm 50 Hz, 10 V/cm 500 Hz, 5 V/cm 50 Hz and 5 V/cm 500 Hz) could achieve a comparable inactivation effect with CH, while OH treatments significantly shortened the processing time. OH treated cells exhibited significantly higher leakage of metal ions (Mg2+ and K+) and biomacromolecules (nucleic acids and proteins) than those treated with CH when bacterial suspensions were heated to the same temperature. Moreover, OH treatment caused more damage on membrane structure, greatly decreased the cell membrane potential and endogenous enzyme activity than that of CH. The results of this study indicated that OH is more efficient in the inactivation of bacteria.

Effects of various parameters on solution-mediated phase transformation of calcium d-gluconate: an approach to obtain pure metastable monohydrate.

The high risk of solution-mediated phase transformation (SMPT) from the metastable monohydrate to stable Form I makes it difficult to produce pure metastable monohydrate of calcium d-gluconate. In this work, we explored the effect of various operating parameters on the SMPT of calcium d-gluconate in water and proposed an effective approach to obtain the desired monohydrate. First, the two forms of calcium d-gluconate were characterized and compared using powder X-ray diffraction (PXRD), thermal analysis, and Raman spectroscopy. The lower solubility of Form I in water illustrates its higher thermodynamic stability than monohydrate when the temperature is higher than 292 K. Afterward, the SMPT of calcium d-gluconate from monohydrate to Form I was investigated in water using in situ Raman spectroscopy combined with scanning electron microscopy and PXRD. Results showed that the nucleation and growth of Form I was the rate-limiting step in the SMPT from monohydrate to Form I. The phase transformation from monohydrate to Form I was delayed to produce pure monohydrate by decreasing temperature and agitation rate, reducing the amount of solid loading, and increasing the particle size of solid loading. Furthermore, the transformation kinetics were studied by the JMA model to explore how temperature influences the SMPT process. This study enriches the study of the calcium d-gluconate SMPT mechanism, and also provides guidance for obtaining high-quality injection-grade calcium gluconate monohydrate.

Nrf2-mediated protective effect of alpha-lipoic acid on synaptic oxidative damage and inhibition of PKC/ERK/CREB pathway in bisphenol A-exposed HT-22 cells.

The harmful effects of bisphenol A (BPA) on learning and memory may involve hippocampal oxidative damage; however, the underlying mechanism remains unclear. Antioxidants that antagonize BPA-induced neuronal oxidative damage lack research. This study aimed to develop an in vitro model using the HT-22 mouse hippocampal neuronal cell line to investigate the neurotoxic mechanism of BPA and the protective effect of alpha-lipoic acid (ALA) on nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition. The results showed that ALA reduced BPA-induced reactive oxygen species and neuronal nitric oxide synthase (nNOS) levels; however, inhibiting Nrf2 weakened the protective effects of ALA. BPA reduced mitochondrial complex I/III activity and ATP levels, but ALA ameliorated this damage. ALA improved the BPA-induced downregulation of the kelch-like ECH-associated protein 1 (keap1)/Nrf2 system, synaptic-related proteins, and the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway; however, the protective effects of ALA were weakened when Nrf2 was inhibited. Our results suggest that BPA causes oxidative damage to HT-22 cells by damaging mitochondrial function, nNOS, and the keap1/Nrf2 system, thereby impairing synaptic-related proteins and the PKC/ERK/CREB pathway. ALA counters BPA-induced damage via Nrf2, which may be a significant target for the protective action of ALA.

Transcriptomic evidence of hypothalamus for maternal fructose exposure induced offspring hypertension through AT1R/TLR4 pathway.

Maternal fructose exposure during pregnancy and lactation has been shown to contribute to hypertension in offspring, with long-term effects on hypothalamus development. However, the underlying mechanisms remain unclear. In this study, we used the tail-cuff method to evaluate the effects of maternal fructose drinking exposure on offspring blood pressure levels at postpartum day 21 (PND21) and postpartum day 60 (PND60). We employed Oxford Nanopore Technologies (ONT) full-length RNA sequencing to investigate the developmental programming of the PND60 offspring's hypothalamus and confirmed the presence of the AT1R/TLR4 pathway using western blot and immunofluorescence. Our findings demonstrated that maternal fructose exposure significantly increased blood pressure in PND60 offspring but not in PND21 offspring. Additionally, we observed transcriptome-wide alterations in the hypothalamus of PND60 offspring following maternal fructose exposure. Overall, our study provides evidence that maternal fructose exposure during pregnancy and lactation may alter the transcriptome-wide of offspring hypothalamus and activate the AT1R/TLR4 pathway, leading to hypertension. These findings may have important implications for the prevention and treatment of hypertension-related diseases in offspring exposed to excessive fructose during pregnancy and lactation.

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.

[Effect of bisphenol A exposure during early development on body weight and glucose metabolism of female filial rats].

OBJECTIVE: To investigate the effect of bisphenol A (BPA) exposure during early development on body weight and glucose metabolism of female filial rats. METHODS: Pregnant Sprague-Dawley rats were exposed by drinking water containing 1 microg/ml BPA from the 6th day of gestation to the end of lactation. Body weight of female pups was measured on born, during lactation and after weaning. The levels of fasting blood glucose, insulin and leptin, the weight of liver and kidney and peri-gonadal and peri-renal adipose tissue were measured, and the organ and adipose tissue coefficients were calculated. RESULTS: Compared with the control pubs, the body weight of pups in BPA-exposed group was significantly higher at born and after weaning, the virginal and gonadal adipose tissue coefficient was significantly higher, and the levels of fasting blood glucose, serum insulin were increased but leptin decreased. CONCLUSION: BPA exposure during early development could increase the body weight and result in insulin resistance. The decrease of serum leptin resulted from BPA exposure maybe one of reasons related to obesity and insulin resistance.

Gut Microbiota Variations between Henoch-Schonlein Purpura and Henoch-Schonlein Purpura Nephritis.

Background: In China, little is known regarding the differences between children with Henoch-Schonlein purpura (HSP) and Henoch-Schonlein purpura nephritis (HSPN) concerning their gut microbiota. Methods: We recruited 25 children with HSP, 25 children with HSPN, and 25 healthy children to investigate the differences. Fecal samples were collected and analyzed by sequencing the V3-V4 region of the 16S rRNA gene. The diversity of the fecal gut microbiota was compared between the patient groups. Results: Rarefaction curves showed that the gut microbial diversity between the three groups differed significantly (P = 0.0224). The top five most abundant gut microbial genera were Bacteroides, Faecalibacterium, Prevotella, Ruminococcaceae, and Megamonas in children with HSP; Bacteroides, Faecalibacterium, Prevotella, Bifidobacterium, and Ruminococcaceae in children with HSPN; and Bacteroides, Prevotella, Faecalibacterium, Ruminococcaceae, and Bifidobacterium in healthy children. Children with HSP had the lowest Bifidobacterium abundance among the three groups (P < 0.05). Children with HSPN had a lower abundance of Akkermansia than children with HSP (P < 0.05), whereas children with HSPN had a higher Alistipes abundance than children with HSP (P < 0.05). Fecal microbial community composition did not differ significantly between groups (ANOSIM, R = -0.002, P = 0.46). Despite the small sample size, our results indicate that children with HSP or HSPN displayed dysbiosis of the gut microbiota. Conclusion: This study provides valuable insights that will benefit the development of future microbe-based therapies to improve clinical outcomes or prevent the incidence of HSP or HSPN in children.

Association of waist circumference with blood pressure and familial dietary habits in preschool children: a cross-sectional study in northeastern China.

BACKGROUND: Childhood obesity increases the risk of elevated blood pressure (BP) in children. Body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) are traditional obesity indices, but the extent to which these indices are associated with elevated BP in childhood remains debatable. Moreover, the familial dietary environment plays an important role in obesity, so it is necessary to determine the most relevant dietary factors for childhood obesity to prevent elevated BP. Our study aimed to identify the obesity indices that are most closely associated with elevated BP and then to determine the independent familial dietary factors for those obesity indices. METHOD: A total of 605 children aged 2 to 6 years, as well as their parents, were involved in this study. The weight, height, WC and BP of the children were measured. Information on familial environments was obtained by questionnaires completed by the parents. BMI, WC and WHtR were standardized into z scores, and categorical variables of these three obesity indices were defined as BMI Category, WC Category and WHtR Category. Logistic regression was used to analyse the associations between all obesity indices and elevated BP. Multivariate linear regression and logistic regression were used to determine the independent factors for obesity indices. RESULTS: The obesity indices that were most closely associated with elevated BP were WC and WC Category. Parental BMI, birth weight, eating wheat as a staple food, appetite, eating speed, snacking while watching TV, parental encouragement to eat a diverse assortment of foods and drinking milk were independently associated with WC in both males and females. The risk of abdominal obesity increased 1.375 times in males and 1.631 times in females if appetite increased one level. If eating speed increased one level, the risk of abdominal obesity increased 1.165 times in males and 0.905 times in females. Females who drank milk more than 6 times per week had a 0.546 times lower risk of abdominal obesity. CONCLUSION: WC was an anthropometric parameter more closely associated with elevated BP. In addition to genetics, some familial dietary factors involving eating preference, eating habits and parental feeding practice were independently associated with WC and abdominal obesity in preschool children.

Learning and memory impairment and transcriptomic profile in hippocampus of offspring after maternal fructose exposure during gestation and lactation.

Increased fructose intake is a global issue, especially in mothers. Maternal fructose exposure during gestation and lactation can affect learning and memory in offspring; however, the detailed mechanism is still unknown. The hippocampus is a mind locale liable for learning and memory. Here, we established a maternal high-fructose diet model by administering 13% and 40% fructose water, applied the Morris Water Maze test on postnatal day 60 offspring, and performed full-length RNA sequencing using the Oxford Nanopore Technologies platform to explore the changes in gene expression in the hippocampus. The results showed that learning and memory in offspring were negatively affected. Compared with the control group, 369 differentially expressed transcripts (DETs) were identified in the 13% fructose group, and 501 DETs were identified in the 40% fructose group. Gene Ontology enriched term and Kyoto Encyclopedia of Genes and Genomes enriched pathway analyses identified several terms and pathways related to brain development and cognitive function. Furthermore, we confirmed that the Wnt/ß-catenin signaling pathway was down-regulated and neuron degeneration was enhanced. In summary, our results indicate that maternal fructose exposure during gestation and lactation can impair learning and memory in offspring and affect brain function at the transcriptome level.

Exercise-Induced Browning of White Adipose Tissue and Improving Skeletal Muscle Insulin Sensitivity in Obese/Non-obese Growing Mice: Do Not Neglect Exosomal miR-27a.

Exercise is considered as a favorable measure to prevent and treat childhood obesity. However, the underlying mechanisms of exercise-induced beneficial effects and the difference between obese and non-obese individuals are largely unclear. Recently, miR-27a is recognized as a central upstream regulator of proliferator-activated receptor γ (PPAR-γ) in contributing to various physiological and pathological processes. This study aims to explore the possible cause of exercise affecting white adipose tissue (WAT) browning and reversing skeletal muscle insulin resistance in obese/non-obese immature bodies. For simulating the process of childhood obesity, juvenile mice were fed with a basal diet or high-fat diet (HFD) and took 1 or 2 h swimming exercise simultaneously for 10 weeks. The obese animal model was induced by the HFD. We found that exercise hindered HFD-induced body fat development in growing mice. Exercise modified glucolipid metabolism parameters differently in the obese/non-obese groups, and the changes of the 2 h exercise mice were not consistent with the 1 h exercise mice. The level of serum exosomal miR-27a in the non-exercise obese group was increased obviously, which was reduced in the exercise obese groups. Results from bioinformatics analysis and dual-luciferase reporter assay showed that miR-27a targeted PPAR-γ. Exercise stimulated WAT browning; however, the response of obese WAT lagged behind normal WAT. In the HFD-fed mice, 2 h exercise activated the IRS-1/Akt/GLUT-4 signaling pathway in the skeletal muscles. In summary, our findings confirmed that exercise-induced beneficial effects are associated with exercise duration, and the response of obese and non-obese bodies is different. Exosomal miR-27a might be a crucial node for the process of exercise-induced browning of WAT and improving skeletal muscle insulin sensitivity.