Dopamine Pretreatment Protects Offspring Rats from LPS-Induced Hypertension and Kidney Damage by Inhibiting NLRP3 Activation in Kidney

This study was designed to explore the role of dopamine (DA) and NLRP3 in the mechanism of hypertension and renal impairment induced by prenatal exposure to lipopolysaccharide (LPS). Thirty pregnant rats were randomly divided into three groups, including control, LPS, and DA + LPS groups. Renal morphology changes were observed under microscope. The serum IL-1β and IL-18 concentration, mRNA, and protein expressions of NLRP3, ASC, and CASP1 in kidney of three-month old offspring rats were measured. Hematoxylin–eosin staining showed that the glomerular diameter decreased and cysts increased partly, glomerular balloons were adhered partly, there were moderate-to-severe hyperplasia dispersedly distributed in glomerular mesangial matrix in rats of LPS group. Serum IL-1β and IL-18 concentration in LPS group increased compared with control group and DA + LPS group. The average arterial pressure of offspring rats in LPS group increased significantly compared with control group and DA + LPS group. NLRP3 mRNA level in the LPS group increased significantly compared with the control group and the DA + LPS group in both male and female rats; NLRP3, ASC, and CASP1 protein expression in both renal cortex and renal medulla of LPS group increased significantly compared with control group and DA + LPS group in female rats. NLRP3 protein expression in LPS group increased significantly compared with control group and DA + LPS group in male rats. DA pretreatment exerts a protective effect on LPS-induced renal injury and hypertension in offspring rats, and the mechanism might be through inhibiting NLRP3 activation.     

Group V Secretory Phospholipase A2 Is Involved in Tubular Integrity and Sodium Handling in the Kidney

Group V (GV) phospholipase A₂ (PLA₂) is a member of the family of secreted PLA₂ (sPLA2) enzymes_. This enzyme has been identified in several organs, including the kidney. However, the physiologic role of GV sPLA₂ in the maintenance of renal function remains unclear. We used mice lacking the gene encoding GV sPLA₂ (Pla2g5^−/−) and wild-type breeding pairs in the experiments. Mice were individually housed in metabolic cages and 48-h urine was collected for biochemical assays. Kidney samples were evaluated for glomerular morphology, renal fibrosis, and expression/activity of the (Na⁺ + K⁺)-ATPase α1 subunit. We observed that plasma creatinine levels were increased in Pla2g5^−/− mice following by a decrease in creatinine clearance. The levels of urinary protein were higher in Pla2g5^−/− mice than in the control group. Markers of tubular integrity and function such as γ-glutamyl transpeptidase, lactate dehydrogenase, and sodium excretion fraction (FE_Na⁺) were also increased in Pla2g5^−/− mice. The increased FE_Na⁺ observed in Pla2g5^−/− mice was correlated to alterations in cortical (Na⁺ + K⁺) ATPase activity/ expression. In addition, the kidney from Pla2g5^−/− mice showed accumulation of matrix in corticomedullary glomeruli and tubulointerstitial fibrosis. These data suggest GV sPLA₂ is involved in the maintenance of tubular cell function and integrity, promoting sodium retention through increased cortical (Na⁺ + K⁺)-ATPase expression and activity.     

Maternal Testosterone and Offspring Sex-Ratio in Birds and Mammals: A Meta-Analysis

Sex allocation theory predicts that parents should bias offspring sex to maximize their fitness in a given context. Quantifying the fitness benefits of offspring sex-ratio biases would be facilitated by a better knowledge of their underlying mechanism(s) and associated costs. The hypothesis that steroid hormones are involved in sex determination has gained in popularity recently. Being influenced by external stimuli and involved in a range of physiological processes, they could be a ubiquitous mediator of environmental conditions influencing sex-ratio with low fitness costs. Previous studies indicated that higher maternal testosterone levels led to the overproduction of sons around conception in both birds and mammals. We conducted a systematic review (including meta-analysis) of these studies and, as predicted, we found a weak positive and significant overall effect of maternal testosterone on the proportion of sons. Neither taxa, nor the type of study (experimental/observational), or the timing of timing testosterone manipulation/measure were significant predictors of offspring sex-ratio, which may be explained by low statistical power in addition to low variability between effect sizes. Our meta-analysis provides evidence for a general positive influence of maternal testosterone around conception on the proportion of sons across birds and mammals, although less confidently so for the latter. It begs for more large-scale experimental studies, especially on mammals, and ideally in the wild. It may also have some important consequences for the poultry industry.     

Macronutrient Composition and Sodium Intake of Diet Are Associated with Risk of Metabolic Syndrome and Hypertension in Korean Women

Hypertension and hypertriglycemia are the most important contributors to metabolic syndrome (MetS) and cardiovascular disease risk in South Koreans with a relatively lean body mass. These major contributors differ from those identified in Western populations. This study aimed to identify the characteristics of the Korean diet associated with increased risk of MetS, whose prevalence has been steadily increasing in South Korea. On the basis of data collected from 5,320 subjects by the 2007–2008 Korean National Health and Nutrition Examination Survey, 3 dietary patterns were identified using factor analysis and their association with the risk of MetS and its components was examined. The balanced Korean diet, a typical Korean diet of rice and kimchi intake supplemented by a variety of foods had a desirable macronutrient composition and was associated with a lower risk of elevated blood pressure (OR=0.61, 95% CI=0.45–0.84) and hypertriglyceridemia (0.69, 0.49–0.88) in men and a lower risk of elevated blood pressure (0.59, 0.41–0.85) and MetS (0.67, 0.47–0.96) in women. The unbalanced Korean diet, characterized by a high intake of carbohydrates and sodium and little variety, was associated with a higher risk of MetS (1.44, 1.03–2.01) and elevated blood pressure (1.41, 1.00–1.98) in women. The semi-western diet, characterized by a relatively high intake of meat, poultry, and alcohol, was associated with a lower risk of low high-density lipoprotein cholesterol (0.70, 0.54–0.89) in women. Thus, macronutrient composition and sodium intake are associated with the risk of MetS and prehypertension in women. Maintaining a desirable macronutrient composition and avoiding excessive consumption of carbohydrates and sodium should be emphasized for prevention of MetS and hypertension in South Korean women.     

Maternal Diabetes and Cognitive Performance in the Offspring: A Systematic Review and Meta-Analysis

Objective

Diabetes during gestation is one of the most common pregnancy complications associated with adverse health effects for the mother and the child. Maternal diabetes has been proposed to negatively affect the cognitive abilities of the child, but experimental research assessing its impact is conflicting. The main aim of our study was to compare the cognitive function in children of diabetic and healthy pregnant women.

Methods

A systematic review and meta-analysis was conducted through a literature search using different electronic databases from the index date to January 31, 2015. We included studies that assessed the cognitive abilities in children (up to 14 years) of diabetic and non-diabetic mothers using standardized and validated neuropsychological tests.

Results

Of 7,698 references reviewed, 12 studies involving 6,140 infants met our inclusion criteria and contributed to meta-analysis. A random effect model was used to compute the standardized mean differences and 95% confidence interval (CI) were calculated. Infants (1–2 years) of diabetic mothers had significantly lower scores of mental and psychomotor development compared to control infants. The effect size for mental development was -0.41 (95% CI -0.59, -0.24; p<0.0001) and for psychomotor development was -0.31 (95% CI -0.55, -0.07; p = 0.0125) with non-significant heterogeneity. Diabetes during pregnancy could be associated with decreased intelligence quotient scores in school-age children, although studies showed significant heterogeneity.

Conclusion

The association between maternal diabetes and deleterious effects on mental/psychomotor development and overall intellectual function in the offspring must be taken with caution. Results are based on observational cohorts and a direct causal influence of intrauterine hyperglycemia remains uncertain. Therefore, more trials that include larger populations are warranted to elucidate whether gestational diabetes mellitus (GDM) has a negative impact on offspring central nervous system (CNS).     

Associations of Maternal Iron Intake and Hemoglobin in Pregnancy with Offspring Vascular Phenotypes and Adiposity at Age 10: Findings from the Avon Longitudinal Study of Parents and Children

Background

Iron deficiency is common during pregnancy. Experimental animal studies suggest that it increases cardiovascular risk in the offspring.

Objective

To examine the relationship between maternal pregnancy dietary and supplement iron intake and hemoglobin, with offspring’s arterial stiffness (measured by carotid-radial pulse wave velocity), endothelial function (measured by brachial artery flow mediated dilatation), blood pressure, and adiposity (measured by body mass index), test for mediation by cord ferritin, birth weight, gestational age, and child dietary iron intake, and for effect modification by maternal vitamin C intake and offspring sex.

Design

Prospective data from 2958 mothers and children pairs at 10 years of age enrolled in an English birth cohort, the Avon Longitudinal Study for Parents and Children (ALSPAC), was analysed.

Results

2639 (89.2%) mothers reported dietary iron intake in pregnancy below the UK reference nutrient intake of 14.8 mg/day. 1328 (44.9%) reported taking iron supplements, and 129 (4.4%) were anemic by 18 weeks gestation. No associations were observed apart from maternal iron intake from supplements with offspring systolic blood pressure (−0.8 mmHg, 99% CI −1.7 to 0, P = 0.01 in the sample with all relevant data observed, and −0.7 mmHg, 99% CI −1.3 to 0, P = 0.008 in the sample with missing data imputed).

Conclusion

There was no evidence of association between maternal pregnancy dietary iron intake, or maternal hemoglobin concentration (which is less likely to be biased by subjective reporting) with offspring outcomes. There was a modest inverse association between maternal iron supplement intake during pregnancy with offspring systolic blood pressure at 10 years.     

Prenatal Exposure to Maternal Bereavement and Childbirths in the Offspring: A Population-Based Cohort Study

IntroductionThe decline in birth rates is a concern in public health. Fertility is partly determined before birth by the intrauterine environment and prenatal exposure to maternal stress could, through hormonal disturbance, play a role. There has been such evidence from animal studies but not from humans. We aimed to examine the association between prenatal stress due to maternal bereavement following the death of a relative and childbirths in the offspring.ResultsA total of 4,121,596 subjects were followed-up until up to 41 years of age. Of these subjects, 93,635 (2.3%) were exposed and 981,989 (23.8%) had at least one child during follow-up time. Compared to unexposed, the hazard ratio (HR) [95% confidence interval] of having at least one child for exposed males and females were 0.98 [0.96–1.01] and 1.01 [0.98–1.03], respectively. We found a slightly reduced probability of having children in females born to mothers who lost a parent with HR = 0.97 [0.94–0.99] and increased probability in females born to mothers who lost another child (HR = 1.09 [1.04–1.14]), the spouse (HR = 1.29 [1.12–1.48]) or a sibling (HR = 1.13 [1.01–1.27]).ConclusionsOur results suggested no overall association between prenatal exposure to maternal stress and having a child in early adulthood but a longer time of follow-up is necessary in order to reach a firmer conclusion.     

Maternal Genes and Facial Clefts in Offspring: A Comprehensive Search for Genetic Associations in Two Population-Based Cleft Studies from Scandinavia

Background

Fetal conditions can in principle be affected by the mother''s genotype working through the prenatal environment.

Methodology/Principal Findings

Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which we focused on fetal gene effects [1]. After data-cleaning, genotypes for 1315 SNPs in 334 autosomal genes were available for the current analysis of maternal gene effects. Two complementary statistical methods, TRIMM and HAPLIN, were used to detect multi-marker effects in population-based samples from Norway (562 case-parent and 592 control-parent triads) and Denmark (235 case-parent triads). We analyzed isolated cleft lip with or without cleft palate (iCL/P) and isolated cleft palate only (iCP) separately and assessed replication by looking for genes detected in both populations by both methods. In iCL/P, neither TRIMM nor HAPLIN detected more genes than expected by chance alone; furthermore, the selected genes were not replicated across the two methods. In iCP, however, FLNB was identified by both methods in both populations. Although HIC1 and ZNF189 did not fully satisfy our stringency criterion for replication, they were strongly associated with iCP in TRIMM analyses of the Norwegian triads.

Conclusion/Significance

Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes.     

Effect of an Excess Intake of Casein Hydrolysate Containing Val-Pro-Pro and Ile-Pro-Pro in Subjects with Normal Blood Pressure,High-Normal Blood Pressure,or Mild Hypertension

A double-blind, placebo-controlled, randomized clinical trial was conducted to evaluate the effects of ingesting an excess of tablets containing casein hydrolysate, incorporating angiotensin I-converting enzyme (ACE) inhibitory peptides such as Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), in subjects with blood pressure ranging from normal to mild hypertension. A total of 48 subjects were given either 5 times more than the effective amount of casein hydrolysate or a placebo in tablet form for 4 weeks. In the active group, systolic blood pressure (SBP) decreased significantly as compared with the placebo group. In stratified analysis, however, this antihypertensive effect was not found in normotensive subjects. In addition, neither an acute or nor an excessive reduction in blood pressure nor clinically important adverse events were observed in this study. These findings suggest that intake of a 5-fold excess of tablets containing casein hydrolysate can lead to a mild improvement in hypertension without side effects.     

Maternal Socioeconomic Status and the Risk of Congenital Heart Defects in Offspring: A Meta-Analysis of 33 Studies

Background

We conducted this meta-analysis to address the open question of a possible association between maternal socioeconomic status and congenital heart defects (CHDs).

Methods

We searched MEDLINE and EMBASE from their inception to January 1, 2014 for case-control and cohort studies that assessed the association between maternal socioeconomic status and the risk of CHDs. Study-specific relative risk estimates were polled according to random-effect or fixed-effect models.

Results

From 3343 references, a total of 31 case-control studies and 2 cohort studies were enrolled in this meta-analysis, including more than 50,000 cases. We observed that maternal educational attainment, family income and maternal occupation were negatively associated with an 11% (pooled RR = 1.11, 95% CI: 1.03, 1.21), 5% (pooled RR = 1.05, 95% CI: 1.01, 1.09) and 51% (pooled RR = 1.51, 95% CI: 1.02, 2.24) increased risk of CHDs, respectively. In a subgroup analysis by geographic region, the results were inconsistent for the European region (RR = 1.29, 95% CI: 0.99–1.69) and USA/Canada region (RR = 1.06, 95% CI: 0.97, 1.16) in maternal educational attainment.

Conclusion

In summary, this meta-analysis suggests that a lower degree of maternal socioeconomic status is modestly associated with an increased risk of CHDs. However, further investigations are needed to confirm the association.     

Different Roles for Lactococcal Aggregation Factor and Mucin Binding Protein in Adhesion to Gastrointestinal Mucosa

Adhesion of bacteria to mucosal surfaces and epithelial cells is one of the key features for the selection of probiotics. In this study, we assessed the adhesion property of Lactococcus lactis subsp. lactis BGKP1 based on its strong autoaggregation phenotype and the presence of the mucin binding protein (MbpL). Genes involved in aggregation (aggL) and possible interaction with mucin (mbpL), present on the same plasmid pKP1, were previously separately cloned in the plasmid pAZIL. In vivo and in vitro experiments revealed potentially different physiological roles of these two proteins in the process of adherence to the intestine during the passage of the strain through the gastrointestinal tract. We correlated the in vitro and in vivo aggregation of the BGKP1-20 carrying plasmid with aggL to binding to the colonic mucus through nonspecific hydrophobic interactions. The expression of AggL on the bacterial cell surface significantly increased the hydrophobicity of the strain. On the other hand, the presence of AggL in the strain reduced its ability to adhere to the ileum. Moreover, MbpL protein showed an affinity to bind gastric type mucin proteins such as MUC5AC. This protein did not contribute to the binding of the strain to the ileal or colonic part of the intestine. Different potential functions of lactococcal AggL and MbpL proteins in the process of adhesion to the gastrointestinal tract are proposed.     

Maternal Parity and the Risk of Congenital Heart Defects in Offspring: A Dose-Response Meta-Analysis of Epidemiological Observational Studies

Background

Epidemiological studies have reported conflicting results regarding maternal parity and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal parity and CHDs in offspring has not been conducted.

Methods

We searched MEDLINE and EMBASE for articles catalogued between their inception and March 8, 2014; we identified relevant published studies that assessed the association between maternal parity and CHD risk. Two authors independently assessed the eligibility of the retrieved articles and extracted data from them. Study-specific relative risk estimates were pooled by random-effects or fixed-effects models. From the 11272 references, a total of 16 case-control studies and 3 cohort studies were enrolled in this meta-analysis.

Results

The overall relative risk of CHD in parous versus nulliparous women was 1.01 (95% CI, 0.97–1.06; Q = 32.34; P = 0.006; I² = 53.6%). Furthermore, we observed a significant association between the highest versus lowest parity number, with an overall RR = 1.20 (95% CI, 1.10–1.31; (Q = 74.61, P<0.001, I² = 82.6%). A dose–response analysis also indicated a positive effect of maternal parity on CHD risk, and the overall increase in relative risk per one live birth was 1.06 (95% CI, 1.02–1.09); Q = 68.09; P<0.001; I² = 80.9%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among studies. A Galbraith plot was created to graphically assess the sources of heterogeneity.

Conclusion

In summary, this meta-analysis provided a robust estimate of the positive association between maternal parity and risk of CHD.     

Dietary Sodium Intake: Knowledge,Attitudes and Practices in Shandong Province,China, 2011

Objective

To investigate the knowledge, attitudes and practices (KAP) for dietary sodium intake among adult residents of Shandong Province, China

Methods

In 2011, we conducted a cross sectional survey among a representative sample of 15,350 adults aged 18 to 69 years using a standardized questionnaire to assess their KAP for sodium. Variation in the KAPs by gender, and residence location were compared using the Chi-square tests. Predictors for the ‘intention to’ and ‘currently taking action to’ reduce sodium intake were determined by multivariate logistic regression with adjustment for confounding factors.

Results

KAPs for dietary sodium intake among urban residents was generally more favorable than among rural residents. Women were likely to have more favorable KAPs than men. About four fifth of subjects reported that they favored a low sodium diets. However, 31% reported that consumption of less sodium results in less physical strength. Overall, 70% indicated their intention to reduce sodium intake, although only 39 % reported that they had taken action to reduce sodium. Multiple logistic regression analyses indicated that favorable actions to dietary sodium reduction were more likely to occur among those who were aware of the link between sodium and hypertension, and less likely among those who had unfavorable attitudes towards dietary sodium reduction.

Conclusion

Increasing knowledge levels about the benefits of sodium reduction will be a key success factor for effective sodium reduction initiatives and is linked to favorable behavioral change. Emphasis should be placed on the rural area.     

Heat Shock Proteins in the “Hot” Mitochondrion: Identity and Putative Roles

The mitochondrion is known as the “powerhouse” of eukaryotic cells since it is the main site of adenosine 5′‐triphosphate (ATP) production. Using a temperature‐sensitive fluorescent probe, it has recently been suggested that the stray free energy, not captured into ATP, is potentially sufficient to sustain mitochondrial temperatures higher than the cellular environment, possibly reaching up to 50 °C. By 50 °C, some DNA and mitochondrial proteins may reach their melting temperatures; how then do these biomolecules maintain their structure and function? Further, the production of reactive oxygen species (ROS) accelerates with temperature, implying higher oxidative stresses in the mitochondrion than generally appreciated. Herein, it is proposed that mitochondrial heat shock proteins (particularly Hsp70), in addition to their roles in protein transport and folding, protect mitochondrial proteins and DNA from thermal and ROS damage. Other thermoprotectant mechanisms are also discussed.