UNASSIGNED: Molecular imaging is a highly effective method for diagnosing cancer and evaluating treatment. A molecular tracer often consists of two segments: A targeting segment, which can be antibodies, antibody fragments, or VHH (nanobody), and a detection segment, such as radioisotopes. The small size of VHH allows for excellent tissue penetration and fast clearance, resulting in minimal nonspecific background, which makes them appealing for use as imaging agents. 99m-technetium (99mTc), one of the well-known radioisotopes, is particularly useful in routine clinical imaging.
UNASSIGNED: This study aims to construct 99mTc-anti-placenta growth factor (PlGF) nanobody and assess its radiochemical purity (RCP).
UNASSIGNED: The mutant form of anti-PlGF nanobody was expressed in E. coli TG1 and purified using Ni-NTA column affinity chromatography. The purified nanobodies were confirmed by SDS-PAGE and western blotting. A 99mTc-tricarbonyl solution was added to phosphate-buffered saline (PBS) containing the mutant nanobody for labeling, and the mixture was purified using a PD-10 column.
UNASSIGNED: The RCP of 99mTc-tricarbonyl is > 98%. After the addition of radioisotopes to the mixture of nanobodies, purity reached 70% in 2 hours and remained constant during incubation. After purifying the labeled nanobody, activity was measured, and the highest amount of labeled nanobodies was collected in the second part. The stability of the labeled nanobody in PBS and in competition with histidine for 4 hours was checked by thin-layer chromatography (TLC).
UNASSIGNED: The findings of this study reveal that the RCP of the labeled nanobody was above 95% after 4 hours, indicating the labeled antibody\'s stability. These results are promising and could be utilized in future in vitro and in vivo studies.

Preeclampsia is characterized by impaired angiogenesis and assessment of angiogenic factors can play a crucial role in the early diagnosis of preeclampsia. The current study reports the levels of angiogenic factors longitudinally from early pregnancy in women with preeclampsia and in the subtypes of preeclampsia, to identify their role in early prediction of preeclampsia. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from 2 hospitals. Blood samples were collected, plasma samples were separated and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery. The current study includes a total of 108 women developed preeclampsia (PE), and 216 matched controls. Angiogenic factors were estimated using commercially available ELISA kits. Receiver operating characteristic (ROC) curves were used to evaluate the potential diagnostic value in the prediction of PE. Lower levels of VEGF, PlGF, and higher levels of sEng and sEng/PlGF ratio (p < 0.05 for all) predate clinical diagnosis in women with preeclampsia. sEng levels and sEng/PlGF ratio showed significant correlation with odds of preeclampsia at all the timepoints. This study identifies a cut off of 33.5 for sFlt-1/PlGF and 25.9 for sEng/PlGF for prediction of early onset preeclampsia. This study reports various angiogenic factors serially across gestation in a general population to identify women at risk of developing preeclampsia and its subtypes. The study also reports a potential biomarker and a pragmatic window for estimation of angiogenic markers to identify women at risk.

BACKGROUND: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively.
METHODS: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays.
RESULTS: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL.
CONCLUSIONS: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.

UNASSIGNED: According to WHO, hypertensive disease is the leading cause of direct maternal mortality accounting for 10-25% in developing countries (James in Heart, 90(12):1499-504). This study compares the combinations of mean arterial pressure (MAP) and uterine artery doppler (UAD) versus serum-free β HCG, pregnancy-associated plasma protein-A, and placental growth factor (PlGF) versus a combination of all variables at 11 to 13+6 as long-term predictors of pregnancy-induced hypertension (PIH).
UNASSIGNED: A prospective, observational cohort study recruited 97 primigravidae at 11 to 13+6 weeks gestation at GMCH. Follow-up was done at 32-34 weeks and before delivery. Development of PIH, mode of delivery, birthweight, maternal and fetal adverse outcomes were documented, analyzed and compared among three groups. In Group A-biophysical markers, Group B-biochemical markers and in Group C all variables were used.
UNASSIGNED: The mean age, maternal weight, height and BMI of patients developing gestational hypertension were 30 ± 5 years, 64.3 ± 12.5 kg, 155.8 ± 5.5 cm and 26.4 ± 4.1, respectively. Out of the 3, Group C is the best screening test for predicting the overall chance of development of gestational hypertension with a sensitivity of 97.37% and specificity of 38.98% (p < 0.0001). A mild negative correlation is seen between PlGF levels and severity of PIH (p-0.0382).
UNASSIGNED: MAP and UAD can be easily incorporated into the infrastructure of most hospitals. If the biochemical test kits are made available at a low cost through available programs such as JSSK, it can bring down the MMR by preventing gestational hypertension.

Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal-fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia\'s genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.

UNASSIGNED: To observe the effect of soya yoghurt (Soyghurt), which is high in flavonoid substance, on the expression of preeclampsia biomarkers (sFLT-1 and PLGF) on preeclampsia serum-induced trophoblast primary cell culture isolated from placental tissue.
UNASSIGNED: The trophoblast primary culture was induced by preeclampsia serum (10%). The Soyghurt treatment was performed with 2.5%, 5%, and 7.5% Soyghurt supernatant concentrations in culture media. The expression of preeclampsia markers, sFLT-1 and PLGF, were evaluated using ELISA.
UNASSIGNED: Expression of sFLT-1 on preeclampsia-induced cell culture treated with Soyghurt was significantly lowered compared to the untreated group (p<0.01). However, no significant difference was observed in the PLGF levels of all groups induced by preeclampsia serum (p>0.05).
UNASSIGNED: This study demonstrates the potential effect of Soyghurt\'s in balancing preeclampsia marker expression by inhibiting the expression of sFLT-1 in preeclampsia serum -induced trophoblast cells.

BACKGROUND: To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction.
METHODS: A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell\'s C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth.
RESULTS: The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell\'s C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell\'s C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell\'s C: 0.68).
CONCLUSIONS: Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level.

OBJECTIVE: During human pregnancy placental extravillous trophoblasts replace the vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling these arteries into distensible low resistance vessels to promote placental perfusion. The present study, determined whether B-flow/ spatio-temporal image correlation (STIC) M-mode ultrasonography provides an in vivo imaging method to digitally quantify spiral artery luminal distensibility, as a physiological index of spiral artery remodeling, during advancing stages of normal human pregnancy.
METHODS: A prospective longitudinal observational study was conducted to quantify spiral artery distensibility, i.e. vessel luminal diameter at systole minus diameter at diastole, by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1), growth factors that modulate events important in spiral artery remodeling, were quantified in a subset of the subjects at the first, second and third semesters.
RESULTS: Median [first quartile, third quartile] spiral artery distensibility progressively increased (P < 0.0001) between the first trimester (0.17 [0.14, 0.21]), second (0.23 [0.18, 0.28]) and third (0.26 [0.21, 0.35]) trimesters of pregnancy. Spiral artery volume flow (ml/cardiac cycle) progressively increased (P < 0.001) between the first 2.49 [1.38, 4.99], second 3.86 [2.06, 6.91] and third 7.79 [3.83, 14.98] trimesters. Coinciding with the elevation in spiral artery distensibility, the median ratio of serum PlGF/sFlt-1 levels increased (P < 0.001) between the first (7.2 [4.5, 10], second (22.7 [18.6, 42.2]) and third (56.2 [41.9, 92.5] trimesters.
CONCLUSIONS: The present study shows that B-flow/STIC M-mode ultrasonography provides an in vivo imaging technology to digitally quantify structural/physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. This article is protected by copyright. All rights reserved.

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UNASSIGNED: This study aims to detect the serum levels of IGF-1, bFGF, and PLGF and their expressions in placental bed tissues of patients with placenta previa complicated with PAS disorders.
UNASSIGNED: This case and control study included 40 multiparous pregnant women with complete placenta previa between 34 weeks and 38 weeks of gestation and they were divided into two groups: 25 patients with PAS (case group) and 15 patients without PAS (control group). The venous blood samples were collected 2 h before the cesarean section, and the placental bed tissues were taken intraoperatively at the placental implantation site and then were histologically examined to evaluate the gravity of the myometrial invasion of the placenta. According to FIGO PAS increasing grading, the 25 patients were also divided into three groups: PAS grade I group, PAS grade II group, and PAS grade III group. The concentrations of IGF-1, bFGF, and PLGF in serum were measured using ELISA, and the mean ratio of the relative mRNA expression of each biomarker in placental bed tissues was calculated using qRT-PCR. The staining intensity and the positive cells were quantitatively measured and expressed as means by using Image J software for IHC analysis.
UNASSIGNED: IGF-1 had low serum levels and high placental bed expression in placenta previa patients with PAS disorders compared to those without PAS (all p < 0.0001). PLGF had high serum levels (p = 0.0200) and high placental bed expression (p < 0.0001) in placenta previa patients with PAS disorders compared to those without PAS. IGF-1 serum levels decreased up to PAS grade II (means were 24.3 ± 4.03, 21.98 ± 3.29, and 22.03 ± 7.31, respectively for PAS grade I, PAS grade II, PAS grade III groups, p = 0.0006). PLGF serum levels increased up to PAS grade II (means were 12.96 ± 2.74, 14.97 ± 2.56, and 14.89 ± 2.14, respectively for the three groups, p = 0.0392). However, IGF-1 and PLGF mRNA placental bed expression increased up to PAS grade III. The relative expression of mRNA means for the three groups was 3.194 ± 1.40, 3.509 ± 0.63, and 3.872 ± 0.70, respectively for IGF-1; and 2.784 ± 1.14, 2.810 ± 0.71, and 2.869 ± 0.48, respectively for PLGF (all p < 0.0001). Their IHC (immunohistochemical) staining also had increasing trends, but p > 0.05. bFGF was not significantly expressed in placenta previa with PAS disorders in most of the analysis sections (p > 0.05).
UNASSIGNED: Low serum levels and high expression in placental bed tissues of IGF-1, or high serum levels and high expression in placental bed tissues of PLGF, may differentiate placenta previa patients with FIGO PAS grade I and PAS grade II from those without PAS disorders. However, they could not significantly predict the degree of placental invasiveness in FIGO PAS grades II and III.