Detection of Urinary Misfolded Proteins for Imminent Prediction of Preeclampsia in Pregnant Women With Suspected Cases: Protocol for a Prospective Noninterventional Study.

BACKGROUND: Preeclampsia (PE) is one of the most common hypertensive diseases, affecting 2%-8% of all pregnancies. The high maternal and fetal mortality rates of PE are due to a lack of early identification of affected pregnant women that would have led to closer monitoring and care. Recent data suggest that misfolded proteins might be a promising biomarker for PE prediction, which can be detected in urine samples of pregnant women according to their congophilia (aggregated) characteristic. OBJECTIVE: The main purpose of this trial is to evaluate the value of the urine congophilia-based detection of misfolded proteins for the imminent prediction of PE in women presenting with suspected PE. The secondary objectives are to demonstrate that the presence of urine misfolded proteins correlates with PE-related maternal or neonatal adverse outcomes, and to establish an accurate PE prediction model by combining misfolded proteins with multiple indicators. METHODS: At least 300 pregnant women with clinical suspicion of PE will be enrolled in this prospective cohort study. Participants should meet the following inclusion criteria in addition to a suspicion of PE: ≥18 years old, gestational week between 20+0 and 33+6, and single pregnancy. Consecutive urine samples will be collected, blinded, and tested for misfolded proteins and other PE-related biomarkers at enrollment and at 4 follow-up visits. Clinical assessments of PE status and related complications for all participants will be performed at regular intervals using strict diagnostic criteria. Investigators and participants will remain blinded to the results. Follow-up will be performed until 42 days postpartum. Data from medical records, including maternal and fetal outcomes, will be collected. The performance of urine misfolded proteins alone and combined with other biomarkers or clinical variables for the prediction of PE will be statistically analyzed. RESULTS: Enrollment started in July 2023 and was still open upon manuscript submission. As of March 2024, a total of 251 eligible women have been enrolled in the study and enrollment is expected to continue until August 2024. Results analysis is scheduled to start after all participants reach the follow-up endpoint and complete clinical data are collected. CONCLUSIONS: Upon completion of the study, we expect to derive an accurate PE prediction model, which will allow for proactive management of pregnant women with clinical suspicion of PE and possibly reduce the associated adverse pregnancy outcomes. The additional prognostic value of misfolded proteins is also expected to be confirmed. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2300074878; https://www.chictr.org.cn/showproj.html?proj=202096. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54026.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.

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Stable isotope technique is important for understanding the structure and function of soil food web, which is considered as a belowground black box. We reviewed typical application cases of stable isotope techniques in the research of soil food webs, including to determine food sources and feeding preferences of soil fauna by using isotopes, and to analyze the trophic structure of soil food webs through isotope fractionation effects during the process of feeding and nutrient sequestration by soil fauna. Additionally, stable isotope techniques could reveal the role of soil biota at different trophic levels within soil food web in ecosystem matter and energy flow, which favored to carry out accurate and efficient research on the contribution of soil food webs to soil carbon and nitrogen cycling process and the corresponding influence mechanism. We further put forward the limitations of current stable isotope techniques and the future development directions.

Exogenous carbon turnover within the soil food web strengthens soil carbon sequestration through microbial necromass accumulation.

Exogenous carbon turnover within soil food web is important in determining the trade-offs between soil organic carbon (SOC) storage and carbon emission. However, it remains largely unknown how soil food web influences carbon sequestration through mediating the dual roles of microbes as decomposers and contributors, hindering our ability to develop policies for soil carbon management. Here, we conducted a 13 C-labeled straw experiment to demonstrate how soil food web regulated the residing microbes to influence the soil carbon transformation and stabilization process after 11 years of no-tillage. Our work demonstrated that soil fauna, as a "temporary storage container," indirectly influenced the SOC transformation processes and mediated the SOC sequestration through feeding on soil microbes. Soil biota communities acted as both drivers of and contributors to SOC cycling, with 32.0% of exogenous carbon being stabilizing in the form of microbial necromass as "new" carbon. Additionally, the proportion of mineral-associated organic carbon and particulate organic carbon showed that the "renewal effect" driven by the soil food web promoted the SOC to be more stable. Our study clearly illustrated that soil food web regulated the turnover of exogenous carbon inputs by and mediated soil carbon sequestration through microbial necromass accumulation.

Antisense oligonuleotides influences trophoblasts behaviors by changing LncNR_040117 expression in antiphospholipid antibody syndrome-induced recurrent pregnancy loss.

OBJECTIVE: The primary objective of this study was to explore whether antisense oligonucleotides (ASOs) that reduce LncNR_040117 expression in patients with antiphospholipid antibody syndrome (APS)-induced recurrent pregnancy loss (RPL), and further decrease apoptosis and improve trophoblasts invasion through mitogen-activated protein kinase (MAPK) pathways. This paper aimed to provide a new strategy to treat APS-induced RPL. METHODS: In this study, we used quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to analyze the expression level of LncNR 040117 in HTR-8/SVneo cells following transfection with ASOs. Then we utilized Western blotting to test the expression levels of interleukin-1ß (IL-1ß), intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and key molecules of MAPK pathways, including the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38. In addition, we examined the HTR-8/SVneo cells apoptosis by cell apoptosis assay, and migration and invasion by transwell antibody assay. Each experiment was repeated three times. The data are presented as the means ± SDs, and statistical comparisons were performed using Student's t-test. p < 0.05 was considered significant. RESULT: Transfected with ASOs, LncNR_040117 was downregulated in trophoblasts compared with APS-induced RPL patients. And LncNR_040117 low expression induced IL-1ß and downstream adhesion molecules ICAM-1 and VCAM-1expression level decreased, as well as MAPK pathways downregulation, including the ERK pathway, JNK pathway and p38/MAPK pathway. Furthermore, all these changes resulted in decreased apoptosis and increased migration and invasion of trophoblasts. CONCLUSION: This study indicated that ASOs that decrease LncNR_040117 expression can reduce apoptosis and enhance the invasion and migration of trophoblasts by regulating the MAPK pathway.

Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome.

Obstetric antiphospholipid syndrome (OAPS) is mediated by antiphospholipid antibodies (aPLs, and anti-ß2 glycoprotein I antibody is the main pathogenic antibody), and recurrent abortion, preeclampsia, foetal growth restriction and other placental diseases are the main clinical characteristics of placental pathological pregnancy. It is a disease that seriously threatens the health of pregnant women. Hydroxychloroquine (HCQ) was originally used as an anti-malaria drug and has now shown benefit in refractory OAPS where conventional treatment has failed, with the expectation of providing protective clinical benefits for both the mother and foetus. However, its efficacy and mechanism of action are still unclear. After clinical data were collected to determine the therapeutic effect, human trophoblast cells in early pregnancy were prepared and treated with aPL. After the addition of HCQ, the proliferation, invasion, migration and tubule formation of the trophoblast cells were observed so that the therapeutic mechanism of HCQ on trophoblast cells could be determined. By establishing an obstetric APS mouse model similar to the clinical situation, we were able to detect the therapeutic effect of HCQ on pathological pregnancy. The normal function of trophoblast cells is affected by aPL. Antibodies reduce the ability of trophoblast cells to invade and migrate and can impair tubule formation, which are closely related to placental insufficiency. HCQ can partially reverse these side effects. In the OAPS mouse model, we found that HCQ prevented foetal death and reduced the incidence of pathological pregnancy. Therefore, HCQ can improve pregnancy outcomes and reverse the aPL inhibition of trophoblast disease. In OAPS, the use of HCQ needs to be seriously considered.

Dok-3 deficient mice display different immune clustering and Tim-3 expression.

BACKGROUND: Dok-3 has been shown to play an important role in immune system. Tim-3 also has been recognized as an important immune regulator which involves in many diseases. The relationship of them is still unclear. METHODS: We detected the expression of Tim-3 on spleen immune cells from Dok-3 deficient mice and control mice by flow cytometry. RESULTS: In this article, we found that Dok-3-/- mice display almost entirely different immune clustering characteristics compared with wild type 129 mice. The CD4 T cells and CD8 T cells decreased and DC cells, macrophages, MDSCs increased when the Dok-3 gene knocked-out. The Tim-3 expression on CD4 T cells, CD8 T cells, NK cells, DC cells increased when the Dok-3 gene knocked-out. The macrophages and MDSCs just display the opposite results. CONCLUSIONS: Although Dok-3-/- mice display different immune clustering and Tim-3 expression, the mechanism still needs further study.