No abstract

Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3β (GSK3β) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine–induced Parkinson’s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3β phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC–PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions.

Although the depth-of-focus in the foveal region has been well investigated, knowledge regarding the effect of retinal eccentricity on blur detection and sensitivity is limited. In the present study, the depth-of-focus at the fovea and in the near retinal periphery (0 degrees -8 degrees ) was assessed psychophysically in 7 human subjects using a 5 mm artificial pupil with accommodation paralyzed. The group mean total depth-of-focus progressively increased linearly from 0.89 D at the fovea to 3.51 D at a retinal eccentricity of 8 degrees at the rate of 0.29 D/degree, with response variability (S.E.M.) remaining relatively constant (+/-0.17 D). We speculate that the reduced detection and sensitivity to blur in the near periphery may be attributed to retinal topography, sharpness overconstancy, optical aberrations, and visual attention in peripheral vision.

To explore the antibiotic body burden of Chinese school children, total urinary concentrations (free and conjugated) of 18 representative antibiotics (5 macrolides, 2 β-lactams, 3 tetracyclines, 4 quinolones, and 4 sulfonamides) were measured by ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry among 1064 school students recruited from 3 economically and geographically distinct areas in east China in 2013. All 18 antibiotics were detected in urine samples with the detection frequencies ranging from 0.4 to 19.6%. The antibiotics were detected in 58.3% of urine samples overall, and this detection frequency reached at 74.4% in one study site. Of them, 47.8% of the urine samples had a sum of mass concentration of all antibiotics between 0.1 (minimum) and 20.0 ng/mL, and 8 antibiotics had their concentrations of above 1000 ng/mL in some urine samples. Three veterinary antibiotics, 4 human antibiotics, and 11 human/veterinary antibiotics were found overall in 6.3, 19.9, and 49.4% of urine samples, respectively. The detection frequencies and concentration levels of antibiotics in urine samples differed by study areas. Concerning mixed exposures, a total of 137 combinations of antibiotics and 20 combinations of antibiotic categories were found overall. Two or more antibiotics or categories were concurrently detected in more than 20% of urine samples. On the basis of a usage analysis, contaminated food or environment might be relevant exposure sources for tetracyclines, quinolones, and sulfonamides.

Mounting evidence has linked postnatal antibiotic use with body mass index (BMI) in children, but the influence of prenatal antibiotic use on offspring obesity risk remains unclear. We aimed to assess the association between fetal exposure to antibiotics and obesity at ages 4 and 7 years among 43,332 children using a multicenter prospective cohort of the US Collaborative Perinatal Project (1959-1976). Antibiotic use was ascertained for mothers during pregnancy. Modified Poisson regression models were used to estimate risk ratios for obesity (BMI >95th percentile), and linear mixed models were applied to assess the association with BMI z score. Repeated prenatal exposure to antibiotics was associated with childhood obesity at age 7 years, and risk of obesity tended to increase with an increasing number of antibiotic exposures (for 2-3 exposures, risk ratio (RR) = 1.22, 95% confidence interval (CI): 1.04, 1.44; for ≥4 exposures, RR = 1.34, 95% CI: 1.03, 1.73). The magnitude of association was strongest for repeated exposures in the second trimester (RR = 1.40, 95% CI: 1.16, 1.71). Prenatal antibiotic use was not associated with obesity or BMI z score at age 4 years. These findings support an increased risk of mid-childhood obesity with repeated use of antibiotics during pregnancy.