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JACC. Advances Nov 2023
PubMed: 38938734
DOI: 10.1016/j.jacadv.2023.100665 -
Journal of Extracellular Biology Jan 2024Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated...
Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells. BeWo and HTR8/SVneo cells were used as placental models and cultured under 5-mM D-glucose (i.e. control) or 25-mM D-glucose (high glucose). Cell-conditioned media (CCM) and cell lysate were collected after 48 h. Different populations of EVs were isolated from CCM by ultracentrifugation (i.e. pellet 2K-g, pellet 10K-g, and pellet 100K-g) and characterised by Nanoparticle Tracking Analysis. Quantitative proteomic analysis (IDA/SWATH) and multiple reaction monitoring protocols at high resolution (MRM) were developed to quantify 37 proteins related to biogenesis, trafficking/release and recognition/uptake of EVs. High glucose increased the secretion of total EVs across the pellets from BeWo cells, an effect driven mainly by changes in the small EVs concentration in the CCM. Interestingly, no effect of high glucose on HTR8/SVneo cells EVs secretion was observed. High glucose induces changes in proteins associated with vesicle trafficking in BeWo cells, including Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9) and Member 8 (HSPA8). For HTR8/SVneo, altered proteins including prostaglandin F2α receptor regulatory protein (FPRP), RAB5A, RAB35, RAB5B, and RB11B, STAM1 and TSG101. These proteins are associated with the secretion and trafficking of EVs, which could explain in part, changes in the levels of circulating EVs in diabetic pregnancies. Further, we identified that proteins RAB11B, PDCD6IP, STAM, HSPA9, HSPA8, SDCBP, RAB5B, RAB5A, RAB7A and ERAP1 regulate EV release in response to high and low glucose when overexpressed in cells. Interestingly, immunohistochemistry analysis of RAB7A revealed distinct changes in placental tissues obtained from women with normal glucose tolerance (NGT, = 6) and those with GDM ( = 6), influenced by diet or insulin treatment. High glucose regulation of proteins involved in intercellular dynamics and the trafficking of multivesicular bodies to the plasma membrane in placental cells is relevant in the context of GDM pregnancies.
PubMed: 38938672
DOI: 10.1002/jex2.135 -
PeerJ 2024Ongoing military conflict in Sudan has had significant repercussions on the health and well-being of the population, particularly among women of reproductive age. This...
OBJECTIVES
Ongoing military conflict in Sudan has had significant repercussions on the health and well-being of the population, particularly among women of reproductive age. This study aimed to investigate the impact of conflict on maternal health by employing a mixed qualitative and quantitative research approach.
METHODS
Through in-depth interviews and survey questionnaires (388 women), this study examined the experiences and challenges faced by pregnant women and new mothers and the availability and accessibility of maternal healthcare services in conflict-affected areas. Using a qualitative approach, in-depth interviews were conducted with 35 women who had recently given birth or were pregnant in regions affected by the Khartoum State-Sudan conflict. Thematic analysis was used to analyze the data collected from the interviews.
RESULT
Most women did not have access to healthcare services (86.6%), and out of the total sample, 93 (24%) experienced adverse outcomes. The factors associated with adverse effects were parity (OR 1.78, CI [1.15-2.75], -value 0.010), gestational age (OR 2.10, CI [1.36-3.25], -value 0.002), access to healthcare (OR 2.35, CI [1.48-3.72], -value 0.001), and delivery mode (OR 1.68, CI [1.05-2.69], = 0.030). Factors significantly associated with accessibility to maternal healthcare services included age (OR, 1.28; = 0.042) and higher conflict levels (1.52 times higher odds, = 0.021). The narratives and experiences shared by women exposed the multifaceted ways in which the conflict-affected maternal health outcomes.
CONCLUSION
The significance of this study lies in its potential to contribute to the existing literature on maternal health in conflict-affected areas, especially in Sudan, and to help us understand how women can receive maternal health services.
Topics: Humans; Female; Sudan; Pregnancy; Adult; Health Services Accessibility; Maternal Health; Maternal Health Services; Qualitative Research; Young Adult; Armed Conflicts; Surveys and Questionnaires; Interviews as Topic; Adolescent
PubMed: 38938615
DOI: 10.7717/peerj.17484 -
PeerJ 2024To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine...
Evaluation of alanine aminotransferase/aspartate aminotransferase ratio and high-density lipoprotein for predicting neonatal adverse outcomes associated with intrahepatic cholestasis of pregnancy.
BACKGROUND
To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine aminotransferase/aspartate aminotransferase (ALT/AST) and high-density lipoprotein (HDL) in predicting adverse neonatal outcomes in women with ICP.
METHODS
A total of 147 pregnant women with ICP admitted to The Fourth Hospital of Shijiazhuang and 120 normal pregnant women in the same period were selected in this study. The Mann-Whitney U test and Chi-square tests were used to compare the differences in clinical data. Multivariate logistic regression was used to analyze the relationship between ALT/AST and the occurrence of adverse pregnancy outcomes in patients with ICP. The combined predictive value of ALT/AST and HDL was determined by receiver operating characteristic (ROC) curve analysis.
RESULTS
Among 147 women with ICP, 122 women had total bile acid (TBA) levels of 10-39.9 µmol/L, and 25 had TBA ≥ 40 µmol/L. There was significantly lower gestational age in patients with severe ICP than in those with mild and control groups (all < 0.05), and the weight of newborns in the maternal ICP group was significantly lower than in the control group ( < 0.05). Increasing TBA levels was associated with higher AST, ALT, ALT/AST, and lower HDL level (all < 0.05). Meanwhile, higher levels of ALT/AST was positively associated with neonatal hyperbilirubinemia [adjusted odds ratio (AOR) = 4.019, 95% CI [1.757-9.194, = 0.001] and cardiac injury [AOR = 3.500, 95% CI [1.535-7.987], = 0.003]. HDL was a significant protective factor for neonatal hyperbilirubinemia and cardiac injury [AOR = 0.315, 95% CI [0.126-0.788], = 0.014; AOR = 0.134 (0.039-0.461), = 0.001]. The area under the ROC curve (AUC) for prediction of neonatal hyperbilirubinemia by ALT/AST combined with HDL was 0.668 [95% CI [56.3-77.3%], = 0.002], and the sensitivity and specificity were 47.1% and 84.0%, respectively. To predict neonatal cardiac injury, the AUC value was 0.668 [95% CI [56.4-77.1%], = 0.002], with sensitivity and specificity were 41.2% and 87.1%, respectively.
CONCLUSIONS
The levels of higher ALT/AST and lower HDL were significantly associated with the risk of ICP-related adverse neonatal outcomes. Moreover, ALT/AST combined with HDL has moderate clinical value in predicting the adverse outcomes of neonatal hyperbilirubinemia and cardiac injury.
Topics: Humans; Female; Pregnancy; Cholestasis, Intrahepatic; Pregnancy Complications; Alanine Transaminase; Adult; Aspartate Aminotransferases; Infant, Newborn; Lipoproteins, HDL; Pregnancy Outcome; ROC Curve; Predictive Value of Tests; Biomarkers; Case-Control Studies
PubMed: 38938614
DOI: 10.7717/peerj.17613 -
Frontiers in Endocrinology 2024Endocannabinoids and their -acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy...
OBJECTIVE
Endocannabinoids and their -acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this cross-sectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth.
METHODS
Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated.
RESULTS
Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM- women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (β=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring.
CONCLUSION
The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM- women and was associated with GDM+ offspring growth at 2 months.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier (NCT04263675 and NCT02872402).
Topics: Humans; Endocannabinoids; Milk, Human; Female; Pregnancy; Diabetes, Gestational; Infant, Newborn; Adult; Cross-Sectional Studies; Male; Infant; Child Development
PubMed: 38938519
DOI: 10.3389/fendo.2024.1415630 -
JACC. Advances Dec 2023Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the...
BACKGROUND
Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction.
OBJECTIVES
This study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively.
METHODS
There were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar.
RESULTS
Women with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, = 0.001) and native-T1 ms (β = 10.6 ± 4.9, = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, = 0.02] and native-T1 ms [β = 10.6 ± 5.2, = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82).
CONCLUSIONS
In a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.
PubMed: 38938498
DOI: 10.1016/j.jacadv.2023.100703 -
JACC. Advances Dec 2023
PubMed: 38938492
DOI: 10.1016/j.jacadv.2023.100698 -
Frontiers in Medicine 2024Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a... (Review)
Review
Since its debut in 2011, Non-Invasive Prenatal Testing (NIPT) has continually demonstrated its effectiveness in detecting an expanding number of diseases. NIPT offers a less invasive approach to prenatal chromosomal disease screening, providing prospective parents with vital information to better prepare for their potential pregnancy outcomes. NIPT was primarily designed for screening trisomy 13, 18, and 21. However, its scope has since broadened to encompass microdeletions and autosomal dominant monogenic diseases. Conversely, the normalization of NIPT can have unintended consequences. Some patients opt for NIPT without any medical indications, driven by a desire to remain cautious. This over-screening for chromosomal abnormalities can exacerbate pregnancy-related anxiety, as individuals might feel pressured into taking the test unnecessarily. While NIPT can be highly successful when conducted correctly, it is not infallible, and obstetricians play a crucial role in managing patient expectations. This includes providing genetic counseling to individuals with relevant genetic information regarding their personal and family histories. In the context of NIPT, a bioinformatics analysis is performed on a cell-free DNA (cfDNA) sample extracted from the mother's placenta to determine the fetal fraction (FF). This FF measurement is vital for quality control and ensuring statistical confidence in the test results. Raising awareness among clinicians about the significance of FF enhances patient care and alleviate concerns about the possibility of failed NIPT. This paper aims to explore the ongoing debates and more specifically the significance and pitfalls of NIPT on a psychosocial and ethical scale, all while highlighting the importance of genetic counseling.
PubMed: 38938382
DOI: 10.3389/fmed.2024.1388481 -
JACC. Advances Oct 2023
PubMed: 38938367
DOI: 10.1016/j.jacadv.2023.100592 -
JACC. Advances Oct 2023
PubMed: 38938364
DOI: 10.1016/j.jacadv.2023.100620