The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study.

Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children's digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother-child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.

Impact of Dietary Manganese on Intestinal Barrier and Inflammatory Response in Broilers Challenged with Salmonella Typhimurium.

Growing concern for public health and food safety has prompted a special interest in developing nutritional strategies for removing waterborne and foodborne pathogens, including Salmonella. Strong links between manganese (Mn) and intestinal barrier or immune function hint that dietary Mn supplementation is likely to be a promising approach to limit the loads of pathogens in broilers. Here, we provide evidence that Salmonella Typhimurium (S. Typhimurium, 4 × 108 CFUs) challenge-induced intestinal injury along with systemic Mn redistribution in broilers. Further examining of the effect of dietary Mn treatments (a basal diet plus additional 0, 40, or 100 mg Mn/kg for corresponding to Mn-deficient, control, or Mn-surfeit diet, respectively) on intestinal barrier and inflammation status of broilers infected with S. Typhimurium revealed that birds fed the control and Mn-surfeit diets exhibited improved intestinal tight junctions and microbiota composition. Even without Salmonella infection, dietary Mn deficiency alone increased intestinal permeability by impairing intestinal tight junctions. In addition, when fed the control and Mn-surfeit diets, birds showed decreased Salmonella burdens in cecal content and spleen, with a concomitant increase in inflammatory cytokine levels in spleen. Furthermore, the dietary Mn-supplementation-mediated induction of cytokine production was probably associated with the nuclear factor kappa-B (NF-κB)/hydrogen peroxide (H2O2) pathway, as judged by the enhanced manganese superoxide dismutase activity and the increased H2O2 level in mitochondria, together with the increased mRNA level of NF-κB in spleen. Ingenuity-pathway analysis indicated that acute-phase response pathways, T helper type 1 pathway, and dendritic cell maturation were significantly activated by the dietary Mn supplementation. Our data suggest that dietary Mn supplementation could enhance intestinal barrier and splenic inflammatory response to fight against Salmonella infection in broilers.

Effect of High Dietary Manganese on the Immune Responses of Broilers Following Oral Salmonella typhimurium Inoculation.

Manganese (Mn) is an essential nutrient for both host and pathogen. Recent studies have demonstrated the nutritional immunity of Mn against Salmonella infection in mammals. To investigate the effect of high dietary Mn on immune responses of broilers following Salmonella challenge, 144 1-day-old male broilers were fed a basal diet (containing 20.04 mg Mn/kg) plus an additional 40 (the control group) or 400 mg Mn/kg (the H-Mn group) for 7 days. The 72 broilers in each group were then orally inoculated with 5 × 107 CFUs of Salmonella typhimurium (ATCC#14028) or phosphate-buffered saline. Peripheral blood, spleens, cecal tonsils, and bursa of Fabricius were collected from Salmonella-inoculated and Salmonella-noninoculated broilers (n = 6) at 2 days post inoculation (2 DPI) and 7 days post inoculation (7 DPI). Peripheral blood lymphocyte subpopulations were determined by flow cytometry. The messenger RNA (mRNA) abundance of genes was determined by quantitative real-time polymerase chain reaction. Salmonella counts were higher (P < 0.05) in the H-Mn group than that in the control group at 2 DPI in the cecal contents of Salmonella-inoculated broilers. High dietary Mn increased CD3+CD4+ and CD3+CD8+ percentages in the peripheral blood of Salmonella-inoculated broilers at 2 DPI. Salmonella inoculation increased interleukin (IL)-6 mRNA expression in spleens and bursa of Fabricius at 2 DPI and increased IL-1ß and IL-6 mRNA expression in cecal tonsils at 7 DPI in the H-Mn group. These changes were not observed in the control group. High dietary Mn increased interferon-γ (IFN-γ) in spleens and decreased IFN-γ and IL-12 mRNA expression in cecal tonsils of Salmonella-inoculated broilers at 2 DPI. High dietary Mn decreased IL-17 mRNA expression in the bursa of Fabricius at 7 DPI, but increased this expression in cecal tonsils at 2 and 7 DPI in Salmonella-inoculated broilers. These results suggested that dietary Mn level affected T helper (Th) 1-cytokine reaction in spleens and cecal tonsils, and Th17-mediated immunity in cecal tonsils and the bursa of Fabricius of broilers when challenged with Salmonella.

Long-term effect of dietary overload lithium on the glucose metabolism in broiler chickens.

Lithium, like insulin, activates glycogen synthase and stimulates glucose transport in rat adipocytes. To investigate the effect of dietary overload lithium on glucose metabolism in broiler chickens, one-day-old chicks were fed a basal diet supplemented with 0 (control) or 100mg lithium/kg (overload lithium) for 35days. Compared to controls, glucose disappearance rates were lower (p=0.035) 15-120min after glucose gavage, and blood glucose concentrations were lower (p=0.038) 30min after insulin injection in overload lithium broilers. Overload lithium decreased (p<0.05) glycogen and glucose-6-phosphate concentrations in liver, but increased (p<0.05) their concentrations in pectoralis major. Overload lithium increased (p<0.05) mRNA expression of glucose transporter (GLUT) 3 and GLUT9 in liver, and GLUT1, GLUT3, GLUT8, and GLUT9 in pectoralis major, but decreased (p<0.05) cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in liver and mitochondrial PEPCK in pectoralis major. These results suggest that dietary overload lithium decreases glucose tolerance and gluconeogenesis, but increases insulin sensitivity and glucose transport in broiler chickens.

Dietary overload lithium decreases the adipogenesis in abdominal adipose tissue of broiler chickens.

To investigate the toxic effects of dietary overload lithium on the adipogenesis in adipose tissue of chicken and the role of hypothalamic neuropeptide Y (NPY) in this process, one-day-old male chicks were fed with the basal diet added with 0 (control) or 100mg lithium/kg diet from lithium chloride (overload lithium) for 35days. Abdominal adipose tissue and hypothalamus were collected at day 6, 14, and 35. As a percentage of body weight, abdominal fat decreased (p<0.001) at day 6, 14, and 35, and feed intake and body weight gain decreased during day 7-14, and day 15-35 in overload lithium treated broilers as compared to control. Adipocyte diameter and DNA content in abdominal adipose tissue were significantly lower in overload-lithium treatment than control at day 35, although no significant differences were observed at day 6 and 14. Dietary overload lithium decreased (p<0.01) transcriptional expression of preadipocyte proliferation makers ki-67 (KI67), microtubule-associated protein homolog (TPX2), and topoisomerase 2-alpha (TOP2A), and preadipocyte differentiation transcriptional factors peroxisome proliferator-activated receptor-γ (PPARγ), and CCAAT/enhancer binding protein (C/EBP) α mRNA abundance in abdominal adipose tissue. In hypothalamus, dietary overload lithium influenced (p<0.001) NPY, and NPY receptor (NPYR) 6 mRNA abundance at day 6 and 14, but not at day 35. In conclusion, dietary overload lithium decreased the adipogenesis in abdominal adipose tissue of chicken, which was accompanied by depressing transcriptional expression of adipogenesis-associated factors. Hypothalamic NPY had a potential role in the adipogenesis in abdominal adipose tissue of broilers with a short-term overload lithium treatment.

Dietary iron concentration influences serum concentrations of manganese in rats consuming organic or inorganic sources of manganese.

To determine the effects of dietary Fe concentration on Mn bioavailability in rats fed inorganic or organic Mn sources, fifty-four 22-d-old male rats were randomly assigned and fed a basal diet (2·63 mg Fe/kg) supplemented with 0 (low Fe (L-Fe)), 35 (adequate Fe (A-Fe)) or 175 (high Fe (H-Fe)) mg Fe/kg with 10 mg Mn/kg from MnSO4 or Mn-lysine chelate (MnLys). Tissues were harvested after 21 d of feeding. Serum Mn was greater (P<0·05) in MnLys rats than in MnSO4 rats, and in L-Fe rats than in A-Fe or H-Fe rats. Duodenal divalent metal transporter-1 (DMT1) mRNA was lower (P<0·05) in H-Fe rats than in A-Fe rats for the MnSO4 treatment; however, no significant difference was observed between them for MnLys. Liver DMT1 mRNA abundance was greater (P<0·05) in MnSO4 than in the MnLys group for H-Fe rats. The DMT1 protein in duodenum and liver and ferroportin 1 (FPN1) protein in liver was greater (P<0·05) in the MnSO4 group than in the MnLys group, and in L-Fe rats than in H-Fe rats. Duodenal FPN1 protein was greater (P<0·05) in L-Fe rats than in A-Fe rats for the MnLys treatment, but it was not different between them for the MnSO4 treatment. Results suggest that MnLys increased serum Mn concentration as compared with MnSO4 in rats irrespective of dietary Fe concentration, which was not because of the difference in DMT1 and FPN1 expression in the intestine and liver.

[Study of the dento-facial features in children of Han nationality with normal occlusion in Shandong district].

PURPOSE: To establish the standard values of roentgengraphic cephalometry in children with normal occlusion in Shandong district and to make the facial model. METHODS: 156 children were selected to take lateral cephalograph, and were divided into two groups: mixed dentition and early permanent dentition. Cephalograms were analyzed for all subjects with WinCeph7.0. Data were obtained for student's t test between the two groups and between males and females. RESULTS: The norms with derivation for all measurement of X ray cephalometrical analysis on hard tissues were established. Meanwhile, the difference between males and females was compared and the facial model of children with normal occlusion was made. CONCLUSION: Gender difference was shown in linear measurements, with greater growth in males in general. The growing tendency of children from mixed dentition to early permanent dentition was that the maxilla of the male grows faster while the mandible of the female grows faster.