Preeclampsia Research Articles

Circ_0015382 Regulates the miR-942-5p/NDRG1 Axis to Suppress Trophoblast Cell Functions.

Circular RNAs (circRNAs) are non-coding RNAs that exert vital function in many human diseases, including preeclampsia (PE). Circ_0015382 is considered to be a key regulator of PE progression, so more molecular mechanisms need to be further studied. Real-time quantitative PCR was used to detect the mRNA levels of circ_0015382, miR-942-5p, and N-myc downstream regulated 1 (NDRG1). Western blot analysis was conducted to assess the protein levels. MTT and EdU assays were used to assess cell proliferation. Cell invasion was analyzed by transwell assay. Tube formation assay was conducted to detect cell angiogenesis. Dual-luciferase reporter assay and RNA immunoprecipitation were used to analyze the target relationship between miR-942-5p and circ_0015382 or NDRG1. Our data showed that circ_0015382 and NDRG1 were up-regulated, while miR-942-5p was down-regulated in the placental tissues of PE patients. Trophoblast cell proliferation, invasion, and angiogenesis were promoted by knockdown of circ_0015382. Circ_0015382 could sponge miR-942-5p, and NDRG1 was a target of miR-942-5p. MiR-942-5p inhibitor could reverse the promoting effects of si-circ_0015382 on trophoblast cell functions. Besides, the enhancing effects of miR-942-5p mimic on trophoblast cell proliferation, invasion, and angiogenesis could be eliminated by NDRG1 overexpression. In conclusion, our data showed that circ_0015382 inhibited trophoblast cell proliferation, invasion, and angiogenesis through regulating miR-942-5p/NDRG1 axis, providing a new mechanism for the regulation of PE progression.

Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.

Preeclampsia (PE) is a complex multisystem disease characterized by hypertension of sudden onset (>20 weeks' gestation) coupled with the presence of at least one additional complication, such as proteinuria, maternal organ dysfunction, or uteroplacental dysfunction. Hypertensive states during pregnancy carry life-threatening risks for both mother and baby. The pathogenesis of PE develops due to a dysfunctional placenta with aberrant architecture that releases factors contributing to endothelial dysfunction, an antiangiogenic state, increased oxidative stress, and maternal inflammatory responses. Previous studies have shown a correlation between grade 3 placental calcifications and an elevated risk of developing PE at term. However, little is known about the molecular pathways leading to placental calcification. In this work, we studied the gene and protein expression of c-Jun N-terminal kinase (JNK), Runt-related transcription factor 2 (RUNX2), osteocalcin (OSC), osteopontin (OSP), pigment epithelium-derived factor (PEDF), MSX-2/HOX8, SOX-9, WNT-1, and β-catenin in placental tissue from women with late-onset PE (LO-PE). In addition, we employed von Kossa staining to detect mineral deposits in placental tissues. Our results show a significant increase of all these components in placentas from women with LO-PE. Therefore, our study suggests that LO-PE may be associated with the activation of molecular pathways of placental calcification. These results could be the starting point for future research to describe the molecular mechanisms that promote placental calcification in PE and the development of therapeutic strategies directed against it.

The discrepancy distribution of macrophage subsets in preeclampsia placenta with or without fetal growth restriction from a small cohort.

To identify the effect of distribution characteristic of macrophages on placental function and angiogenesis in pregnancies with preeclampsia (PE) in presence of fetal growth restriction (FGR) or preeclampsia without FGR. The study tested the hypothesis that there was association between distribution characteristic of macrophage subsets (marked by CD68, CD163, respectively) and placental capillary development, leading to placental dysfunction in PE pregnancies with FGR (n = 36). Changes in placental parameters related with efficiency and angiogenesis and macrophage phenotypes (CD68 and CD163) were evaluated by immunohistochemistry. Pearson correlation analysis was performed to analysis the association between macrophage phenotype and placental function as well the CD34 staining, respectively. Additionally, the localization of CD68 and CD163 was assessed by using immunoflurorescence staining. Pearson correlation analysis had shown the positive association between CD68 expression and microvessel formation and the reverse linear relationship between CD163 staining and placental sufficiency in PE + FGR placenta. The co-localization of CD163 and CD34 may pointed to the compensatory role of CD163 distribution involved in prompting neovascularization. The association between disturbed distribution of macrophages and placental efficiency and angiogenesis were only found in PE with FGR not in PE pregnancies without FGR, underlying the discrepancy role of macrophage subsets depending on the clinical phenotype of PE pregnancies.

Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 μg/mL and 510 μg/mL). Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 μg/mL and > 510 μg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 μg/mL and > 510 μg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 μg/mL and > 510 μg/mL. The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 μg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of outcomes and risk factors for recurrent preeclampsia in a subsequent pregnancy.

The aim was to evaluate the pregnancy outcomes and identify risk factors for recurrent preeclampsia (PE). Retrospective analysis of patients discharged with PE between January 1, 2010, and January 1, 2023, from two tertiary referral hospitals. They were classified into recurrent and non-recurrent groups based on the presence of PE in subsequent pregnancies. Among 519 women who had a subsequent pregnancy after a history of PE, 153 developed recurrent PE while 366 did not. The recurrent cases included 81 preterm PE, of which 41 were early-onset PE (EOPE). Recurrent PE correlated significantly with prior EOPE, HELLP syndrome, placental abruption, and stillbirth, as well as with current chronic hypertension (CH) and type 2 diabetes. The recurrent group showed a 5.8-fold higher risk of preterm birth (PTB) compared to the non-recurrent group (50.7% vs. 8.7%). Notably, 58.1% of the PTBs in the non-recurrent group were spontaneous. Logistic regression identified previous EOPE (aOR: 4.22 [95% CI: 2.50-7.13]) and current CH (aOR: 1.86 [95% CI: 1.09-3.18]) as independent contributors for recurrent PE. Furthermore, recurrent preterm PE shared the same risk factors: previous EOPE (aOR: 5.27 [95% CI: 2.82-9.85]) and current CH (aOR: 2.99 [95% CI: 1.57-5.71]). The morbidity of CH in subsequent pregnancy peaked at 31.9% when women with a history of EOPE delivered within three years. Previous EOPE and current CH were sequentially crucial risk factors for the development of PE and preterm PE during the next pregnancy. This may clarify risk stratification in prenatal management for women with a history of PE.

Micronutrient homeostasis disturbances in women with gestational diabetes mellitus and subclinical hypothyroidism: effects on pregnancy and outcomes

Aim. To characterize micronutrient homeostasis in women with a combination of gestational diabetes mellitus (GDM) and subclinical hypothyroidism (SCH), and to determine the significance of micronutrient imbalance in complicated pregnancies.Material and Methods. The study analyzed 439 birth histories of patients with GDM and SCH, who underwent plasma micronutrient analysis at 12−13 weeks of gestation. The study examined the patients' anthropometric and medical history data, complications during the current pregnancy, the timing and method of delivery, and newborn conditions. Some of these indicators were compared with previously obtained plasma micronutrient levels (Al, Co, Cu, Fe and others) measured at 12−13 weeks of gestation.Results. The analysis of micronutrient concentrations in plasma at 12−13 weeks of gestation revealed iron deficiency in 250 patients (57%), iodine deficiency in 231 patients (52.6%), cobalt deficiency in 229 patients (52.2%), vitamin B12 deficiency in 285 patients (64.9%), and vitamin D deficiency in 280 patients (63.6%). Iron deficiency was significantly more common in pregnant women with overweight and obesity than in those with normal body weight (χ2 =.14 and 5.32, respectively). The risk of developing iron deficiency also increased with higher body weight (1.81-fold for overweight (95% CI 1.2–2.73) and 2.07-fold for obesity (95% CI 1.11–3.86). Around 50% of patients with threatened preterm birth had cobalt deficiency and 59% of patients with anemia had iron deficiency. Selenium, calcium, and vitamin B12 deficiencies were observed in 55%, 70%, and 73% of patients with preeclampsia (PE), respectively.Conclusion. The observed deficiency of certain micronutrients in specific pregnancy complications suggests that correcting micronutrient levels during pre-conception or early gestation may improve pregnancy outcomes.

Red blood cell in preeclampsia: attenuated nitric oxide generation and enhanced reactive oxygen species formation and eryptosis

Preeclampsia (PE) pathogenesis is strongly related to diminished nitric oxide (NO) bioavailability and enhanced oxidative stress. Emerging evidence suggests that red blood cells (RBCs) eNOS enzyme contributes to systemic NO bioavailability by its ability of both NO and ROS generation. We aimed to investigate RBC eNOS enzyme activity, NO and ROS generation capacity, eryptosis index and aggregation levels in preeclamptic and uncomplicated pregnant women. Fifty-eight PE patients and 36 healthy pregnant women were included to the investigation. RBC eNOS enzyme activity, intracellular NO, calcium and ROS concentrations and eryptosis levels were determined via flow cytometric methods. RBC deformability and aggregation were measured via LORRCA. Intracellular NO and phosphorylated RBC eNOS levels decreased in PE group compared to healthy pregnant group (p < 0.05, p < 0.001 respectively). Intracellular ROS and calcium levels, eryptosis values and aggregation indexes in the PE group were significantly higher than healthy pregnant group (p < 0.05, p < 0.01, p < 0.05, p < 0.05 respectively). Our results demonstrate for the first time that RBC produce lower NO and higher ROS under PE conditions. Further, RBC of PE patients were more prone to eryptosis and aggregation compared to control group. Our results suggest that, in addition to endothelial cells, RBC also contribute to decreased plasma NO bioavailability via producing less NO and high ROS in PE. Considering increased tendency to eryptosis and aggregation, RBC seem to play role in haemodynamic changes of PE pathogenesis.

Regulatory role and molecular mechanism of METTL14 in vascular endothelial cell injury in preeclampsia.

Preeclampsia (PE) is a pregnancy-related disease characterized by vascular endothelial cell injury. This study aimed to investigate the role of methyltransferase-like protein 14 (METTL14) in vascular endothelial cell injury in PE. The PE cell model was established by treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-alpha (TNF-α) in vitro. METTL14 and forkhead box protein 1 (FOXP1) were silenced, and miR-34a-5p was overexpressed in HUVECs to evaluate their effects. HUVEC viability, apoptosis, and the levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and endothelin-1 were measured. The N6-methyladenosine (m6A) modification of pri-miR-34a-5p was quantified. The interactions between miR-34a-5p, DiGeorge syndrome critical region 8, and m6A enrichment in miR-34a-5p were analyzed. The relationship between miR-34a-5p and FOXP1 was also verified. The results showed that the expressions of METTL14, FOXP1, and miR-34a-5p were determined. METTL14 expression was elevated in the TNF-α-induced HUVEC injury model. Silencing METTL14 improved HUVEC viability, inhibited apoptosis, and reduced endothelial inflammation. METTL14 promoted miR-34a-5p expression through m6A modification. Overexpression of miR-34a-5p or silencing of FOXP1 reversed the protective effects of METTL14 silencing on cell injury in the PE model. In conclusion, METTL14 mediated m6A modification to promote miR-34a-5p expression, leading to the inhibition of FOXP1 expression, which aggravated endothelial cell damage in the PE cell model.

First-trimester uterine artery Doppler and PAPP-A levels as predictors of pre-eclampsia in a South Asian population; Mardan city, Pakistan

One of the most common causes of maternity and neonatal fatalities and mortality is Pre-eclampsia (PE) which is responsible for 14% of global maternal deaths. The condition is primarily attributed to impaired trophoblastic invasion, which increases uterine artery pulsatility index (PI). A predictive analysis was done at Swat Medical College and Women's Hospital in Mardan, Pakistan from June 2022 to June 2023, including 218 pregnant women aged 11-13+6 weeks. Females with multifetal pregnancies, congenital fetal anomalies, and pre-existing medical conditions were excluded from this research. Uterine artery the Doppler and the PAPP-A testing were done to screen the conditions. Of 624 screened women, 218 were included in the final analysis using SPSS. The study population's mean age was 28 years, with 59% primiparous and 41% multiparous women. The incidence of PE was 35.5%, and gestational hypertension was 22.5%. Women developing hypertensive disorders had significantly higher mean uterine artery PI (2.11) compared to normotensive women (1.21, p=0.01), and significantly lower mean PAPP-A MoM levels (0.78 vs. 1.42, p&lt;0.001). Coupled aberrant uterine blood vessels PI and PAPP-A predicted PE with high significance (p&lt;0.001). Uterine artery in the first trimester Doppler and PAPP-A levels are effective in predicting pre-eclampsia in a South Asian population. Implementing these screenings could enhance early detection and management of PE, potentially reducing associated morbidity and mortality.

Features of preeclampsia in patients with chronic kidney disease

Aims: to study the characteristics of preeclampsia (PE) in women with chronic kidney disease (CKD) compared to PE in the general population.Method: a prospective observational study analyzed the course of PE in 24 women with a previously established diagnosis of CKD (Group 1) and 39 women in the general population (Group 2) without a complicating somatic history. In patients with CKD with a known pregestational creatinine level, the physiological response of the kidneys to pregnancy was assessed, defined as a decrease in serum creatinine by more than 10% in the first trimester. The angiogenic ratio (sFlt-1/PLGF) was studied in 13 patients with CKD.Results: the two groups did not differ in age or parity. In the first group, 16 patients had CKD stage 1-2, 5 had CKD 3A, and one patient each had CKD 3B, 4 and 5 (the later receiving hemodialysis). Nineteen (79%) of women with CKD had hypertension, proteinuria (PU), renal impairment or a combination of these factors before conception. Only 3 out of 16 patients had a physiological renal response. Early PE developed in 58.3% of patients with CKD compared to 35.3% in second group (p = 0.082). The duration of PE inversely correlated with the stage of CKD (r = -0.630; p = 0.001). As pregnancy progressed in patients with CKD, PU increased, reaching nephrotic level in 54% of women by the time of PE. HELLP syndrome or isolated hematological signs of TMA were noted in 8 patients in the general population group, and in 1 in the CKD group. The average sFlt-1/PLGF value in patients with early stages of CKD (n = 9) was 81.0±24.0, with late stages (n = 4) it was 14±8.Conclusion: the study identified the features of PE in CKD: early onset, increased PU reaching nephrotic level in half of the cases by the time PE is diagnosed, and the absence of a histological renal response to pregnancy in the 1st trimester. The lack of changes in the angiogenic coefficient in women with PE and late-stage CKD requires further study in a larger group of patients.

Lesser Weeks of Gestation Correlated with Levels of Cortisol in Ghanaian Women with Preeclampsia, Case-control Study

Following the different kinds of treatment of Preeclampsia (PE) that have challenged clinical regimens, it seems expedient to find ways of preventing PE. Cortisol might be the best factor and marker to provide the baseline information, hence the focus. The aim was to determine cortisol levels in preeclampsia. STROBE consensus checklist was utilized for this case-control study. Clinical information on 125 subjects (50 controls, 30 PE, 50 pregnant normotensive; with 5 lost by attrition) was obtained after ethical consideration (MS-Et/M.3 – P.3.2/2013 – 2014) and informed consent. Full blood count, lipid profile, and cortisol levels were analyzed after venipuncture and blood processing from subjects. SPSS version 20 was used to analyze data. The mean cortisol level in PE was 149.37ng/mL and this was statistically significant when compared with non-pregnant normotensive (controls) only (p = 0.004); and likewise, with both pregnant normotensive and controls (p = 0.008). During cortisol stratification, the odds ratio between PE and controls was 0.0927 (p = 0.0001) while the odds between pregnant normotensives and controls was 0.0374 (p &lt; 0.0001). A significant finding was seen between cortisol levels and lesser gestational weeks. The fewer the weeks of gestation, the higher the cortisol level of the preeclamptic patient.

SARS-CoV-2 seroprevalence and preeclampsia markers in Mozambican pregnant women with perinatal loss

BackgroundSARS-CoV-2 infection during pregnancy is known to be associated with poor pregnancy outcomes, including pre-eclampsia (PE), prematurity, perinatal and maternal mortality. Data on the burden of SARS-CoV-2 infection among pregnant women and their offspring in Sub-Saharan Africa is limited. We aimed to estimate SARS-CoV-2 seroprevalence and determine PE biomarkers in Mozambican pregnant women with perinatal loss.MethodsA cross-sectional study was conducted among women who had a fetal or an early neonatal death at the Maputo Central Hospital (MCH), Mozambique. Anti-SARS-CoV-2 IgG/IgM were determined in maternal and umbilical cord blood and PE biomarkers (sFlt-1 and PIGF) in maternal blood. SARS-CoV-2 RT-PCR was performed in placenta and fetal lung biopsies from participants found to be SARS-CoV-2 seropositive.ResultsA total of 100 COVID-19 unvaccinated women were included in the study from March 2021 to April 2022. Total SARS-CoV-2 antibodies were detected in 68 [68%; 95CI (58 – 76)] maternal and 55 [55%; 95CI (54 – 74)] cord blood samples. SARS-CoV-2 IgM was detected in 18 cord blood samples and a positive placental RT-PCR in three of these participants. The proportion of women with moderate to high sFlt-1/PIGF ratio was higher in SARS-CoV-2 seropositive women than in those seronegative (71.2% vs 28.8%, p = 0.339), although the difference was not statistically significant.ConclusionsSARS-CoV-2 seroprevalence among Mozambican women with perinatal loss was high during the second pandemic year, and there was evidence of vertical transmission in stillbirths. Findings also suggest that maternal SARS-CoV-2 infection may increase the risk of developing PE.

Methylation alterations of imprinted genes in different placental diseases

BackgroundImprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS).ResultsIn this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2′-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS.ConclusionsThis study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

Maternal-Fetal Complications in Renal Colic during Pregnancy: A Scoping Review.

Renal colic is one of the most common non-obstetric causes of hospitalization in pregnant women. Its management is often a challenge for obstetricians/gynecologists, urologists and neonatologists due to the complexity of the problem. The aim of this study was to analyze the possible maternal-fetal complications in renal colic during pregnancy. The authors performed a scoping review of the current literature regarding the analyzed issues. The review was conducted using the PubMed/MEDLINE and Web of Science databases. The search generated a total of 237 articles, out of which 7 original studies were ultimately included in the scoping review. In the women affected by renal colic, the incidence of perinatal complications such as urinary tract infections (UTIs), premature rupture of membranes (pPROM), and preterm birth is markedly higher than reported in the general population of pregnant women. Data regarding the recurrence of other perinatal complications such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preeclampsia (PE), and intrauterine growth restriction (IUGR) are scarce and ambiguous. Further research on these issues is needed to improve the perinatal outcomes of the affected pregnancies.

Oxidative Stress and Anti-Carbonic Anhydrase Antibody Levels in Early Preeclampsia: A Clinical Investigation

Objective: Preeclampsia (PE) is a dangerous condition that affects 3–5% of pregnancies and has a substantial risk of death and morbidity for both mothers and newborns. The processes behind the etiology of PE are not entirely known, despite the fact that it is the primary cause of illness and death among mothers globally. In order to further understand the correlations between these parameters, this study will look at the levels and presence of anti-carbonicianhydrase (CA) I and II antibodies, total oxidanticapacity (TOC), total antioxidanticapacity (T-AOC), and malondialdehyde (MDA) in early PE. Methods: The research analyzed 30 pregnant women with early PE and 30 normal pregnant women as the control group. Serumxlevels of anti-CAiI (pg/mL), anti-CAxII (ng/mL), MDA (nmol/mL), TOS (U/mL), T-AOC (U/mL) were measured and compared between the two groups. Results: Significant variations were noted in the amount of anti-CA I, anti-CA II, MDA, TOS, and T-AOC (both p

The Effect of Intrathecal Anesthesia during Emergency Caesarean Section for Severe Preeclampsia and Eclampsia Patients in a Tertiary Care Hospital

Background: Severe preeclampsia and eclampsia are common in Bangladesh and are one of the leading cause of perinatal morbidity and mortality. The aim of the study is to observe the effect and hazards of intrathecal anesthesia for the mangement of caesarean section for severe pre-eclampsia and eclampsia patients. Management of these patients is very much important for the strenuous obstetrician and anesthesiologist both. Materials and Methods: This retrospective observational study was conducted in the Department of Anesthesiology and ICU of the IAHS (Institute of Applied Health Sciences) Chattogram from January 2022 to December 2022. Total 50 ASA grade 1 or 11, aged between 18-40 years, need urgent LSCS of 1-2 hours duration cases were selected purposively for intrathecal anesthesia. Patients with known cardiovascular and pulmonary diseases, fetal distress, severe maternal distress, uncontrolled DM, presence of any contraindication, patient’s refusal for SAB, septicemia, BP&gt;170/120 mmhg, altered coagulation profile, APH, IUD were excluded from this study. Results: Among the study subjects, 30(59.68%) cases were primigravida patients- out of which five had severe pre eclampsia and 25 had eclampsia. Intraoperative shivering was observed in 18(29.03%) cases, postoperative shivering was observed in 16(25.80%) cases. Acute renal failure was found in 3(6%) cases, HELLP syndrome 10%, DIC 8%, abruption placentae 14%, pulmonary edema 4%, septicemia 16%, PPH 12% and postpartum eclampsia 22% cases. Apgar score &lt;7 at 5 minutes in severe PET was observed in 04(6.45%) cases and eclampsia in 07 (14.51%) cases. Among them 10(20.96%) were eclamptic and 02(4.83%) had PET. p value was found 0.000 which is very highly significant. Conclusion: The outcome results of intrathecal anesthesia is better than general anesthesia. IAHS Medical Journal Volume 6(2) December 2023; 58-63

The role of pyroptosis in the occurrence and development of pregnancy-related diseases.

Pyroptosis is a form of programmed cell death that is crucial in the development of various diseases, including autoimmune diseases, atherosclerotic diseases, cancer, and pregnancy complications. In recent years, it has gained significant attention in national and international research due to its association with inflammatory immune overactivation and its involvement in pregnancy complications such as miscarriage and preeclampsia (PE). The mechanisms discussed include the canonical pyroptosis pathway of gasdermin activation and pore formation (caspase-1-dependent pyroptosis) and the non-canonical pyroptosis pathway (cysteoaspartic enzymes other than caspase-1). These pathways work on various cellular and factorial levels to influence normal pregnancy. This review aims to summarize and analyze the pyroptosis pathways associated with abnormal pregnancies and pregnancy complications. The objective is to enhance pregnancy outcomes by identifying various targets to prevent the onset of pyroptosis.

Three transposable elements exhibiting differential expression in pre-eclampsia overlap with enhancer regions

Transposable elements (TEs) play a crucial role in placental development and dysfunction. Our study examined TE expression in pre-eclampsia (PE) using RNA-seq datasets. We identified differentially expressed TEs and explored the genomic location of the most significant TEs, investigating their possible regulatory roles. Notably, three TEs overlapped with putative enhancer regions, suggesting a potential regulatory impact on gene expression. These findings highlight the regulatory potential of TEs and their importance in placental development, supporting that TE dysregulation may contribute to PE pathogenesis.

Roles and action mechanisms of NRIP1 in pre-eclampsia.

Pre-eclampsia (PE) is characterized by the onset of hypertension and proteinuria during pregnancy. Here, we aimed to explore the functions of nuclear receptor-interacting protein 1 (NRIP1) in PE mice and human placental JEG-3 cells. We evaluated its effects on JEG-3 cell proliferation, apoptosis, invasion, and inflammatory response and regulation of Wnt/β-catenin pathway. NRIP1 levels in human serum and placental tissues, JEG-3 cells, and mouse models were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. JEG-3 cell growth, apoptosis, migration, and invasion were evaluated via 5-ethynyl-2'-deoxyuridine, flow cytometry, and transwell assays. Levels of the inflammatory factors, matrix metalloproteinase (MMP)-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were determined via enzyme-linked immunosorbent assay. Wnt/β-catenin pathway was assessed via western blotting and qRT-PCR. Systolic blood pressure and proteinuria were measured using the non-invasive tail cuff method and Coomassie brilliant blue assay, respectively. TdT-mediated dUTP nick-end labeling assay was used to assess cell apoptosis in the placental tissues of PE mice. NRIP1 levels were upregulated in the serum and placental tissues of patients with PE. In vitro experiments revealed that NRIP1-small interfering RNA (siRNA) increased the cell viability, migration, and invasion and reduced the cell apoptosis compared to the control siRNA. Moreover, NRIP1-siRNA activated the Wnt/β-catenin signaling pathway, as indicated by the increased Wnt3a, β-catenin, p-glycogen synthase kinase-3β, c-Myc, and cyclin D1 levels. Levels of the inflammatory factors, IL-6, TNF-α, and MMP-2, were decreased in the NRIP1-siRNA-treated group. Notably, NRIP1 downregulation improved the PE-like symptoms, inhibited the inflammatory responses, and reduced apoptosis in PE mice. This study revealed the crucial roles of NRIP1 in PE. Our findings revealed that NRIP1 downregulation relieved PE symptoms by inhibiting cell proliferation, migration, and invasion via the Wnt/β-catenin pathway, thus providing a novel candidate for PE treatment.

Relation of rs846910, rs4844880 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) polymorphisms with the risk of preeclampsia: A case-control study

BackgroundThe 11β-hydroxysteroid-dehydrogenase 1 (11β-HSD1) enzyme catalyzes the interconversion of cortisone and cortisol, with mainly oxoreductive activity in intact cells due to co-expression with hexose-6-phosphate dehydrogenase (H6PD). The uterine localization of 11β-HSD1 and its reduced placental expression in women with preeclampsia (PE) suggest a role for 11β-HSD1 in PE pathogenesis. We investigated the association of rs4844880 and rs846910 variants in the HSD11B1 gene with PE in Tunisian women. MethodsThe study cases comprised 334 women who presented with PE and 314 age-matched normotensive women who served as controls. The rs4844880 and rs846910 HSD11B1 gene variants were genotyped by real-time PCR. ResultsThe rs4844880 T > A and rs846910 G > A minor allele frequencies were not different between PE cases and control women, which persisted after adjusting for age, BMI, gestational age, premature delivery, and baby weight. An association was noted for rs4844880 A/A genotype with a heightened risk of PE, which persisted after controlling key covariates. The (minor) A allele of rs4844880 was linked with elevated serum ALT and higher serum AST. In contrast, carriage of the rs846910 minor (A) allele was connected with higher baby weight on delivery and serum AST levels. Setting the major allele homozygotes (T-G) as a reference, a higher prevalence of double minor allele (A-A) haplotype was seen in PE cases than in corresponding controls, which persisted after controlling for age and BMI. Controlling for gestational age and baby weight identified the T-A haplotype and confirmed the association of the A-A haplotype with a heightened risk of PE. ConclusionOur results support an association between HSD11B1 polymorphisms and increased risk of PE and PE-associated clinical features.