Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Evaluation of Taraxacum mongolicum flavonoids in diets for Channa argus based on growth performance, immune responses, apoptosis and antioxidant defense system under lipopolysaccharide stress.

To ascertain the effects of Taraxacum mongolicum flavonoids (TMF) on the growth performance, digestive enzyme activity, immune indices, inflammatory response and antioxidant capacity of Channa argus, 400 C. argus with an average body weight of (8.08 ± 0.21) g were selected and divided randomly into four groups. They were fed with four experimental diets supplemented with TMF of 0 (control), 25, 50 and 100 mg/kg for 56 d, and then challenged with lipopolysaccharide (LPS) for 96 h, afterwards indices were detected. The results manifested that the addition of TMF above 50 mg/kg in the dietary could significantly improve the final body weight, WGR, SGR and PER of C. argus, while decreased FCR (P < 0.05). Similarly, the 50 mg/kg group had the highest activity of digestive enzymes (protease, lipase, amylase) in intestine and hepatopancreas, which were notably higher than those in the control group (P < 0.05). Nevertheless, 100 mg/kg group could effectively inhibit the liver and gut injury caused by LPS and reduce the contents of ALT and AST, LPS and LBP in serum. In the immune (LY, AKP, ACP, IgM, C3) and antioxidant (T-AOC, SOD, CAT, GSH-PX, GR, ASA, MDA) systems, 100 mg/kg groups were the optimal group, which were remarkably higher than those of the control group (P < 0.05). Additionally, the expression of genes revealed that 100 mg/kg group could noteworthy restrain the expression of pro-inflammatory factors (tnf-α, il-1ß, il-8) and pro-apoptosis (cas-3,8,9, p53, bax, bcl-2) related genes, up-regulate the expression of anti-inflammatory (il-10, tgf-ß) factors, antioxidant-related (nrf2, gpx, gst, cat) genes and heat shock proteins (hsp70, hsp90). Simultaneously, the survival rate of C. argus in the 100 mg/kg TMF-supplemented group was the highest after LPS challenge. Our results elucidate that dietary supplementation TMF protects C. argus from LPS-induced inflammatory injury, to ameliorate digestion, immune response, antioxidant status and apoptosis, implying that TMF could be regarded as an anti-inflammatory and antioxidant agent adding to aquatic animal feed.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.