Construction of a pathway-level model for preeclampsia based on gene expression data.

Preeclampsia (PE) is a heterogeneous disease that seriously affects the health of mothers and fetuses. Lack of detection assays, its diagnosis and intervention are often delayed when the clinical symptoms are atypical. Using personalized pathway-based analysis and machine learning algorithms, we built a PE diagnosis model consisting of nine core pathways using multiple cohorts from the Gene Expression Omnibus database. The model showed an area under the receiver operating characteristic (AUROC) curve of 0.959 with the data from the placental tissue samples in the development cohort. In the two validation cohorts, the AUROCs were 0.898 and 0.876, respectively. The model also performed well with the maternal plasma data in another validation cohort (AUROC: 0.815). Moreover, we identified tyrosine-protein kinase Lck (LCK) as the hub gene in this model and found that LCK and pLCK proteins were downregulated in placentas from PE patients. The pathway-level model for PE can provide a novel direction to develop molecular diagnostic assay and investigate potential mechanisms of PE in future studies.

Overexpressed Trophoblast Glycoprotein Contributes to Preeclampsia Development by Inducing Abnormal Trophoblast Migration and Invasion Toward the Uterine Spiral Artery.

BACKGROUND: Preeclampsia is a significant pregnancy disorder with an unknown cause, mainly attributed to impaired spiral arterial remodeling. METHODS: Using RNA sequencing, we identified key genes in placental tissues from healthy individuals and preeclampsia patients. Placenta and plasma samples from pregnant women were collected to detect the expression of TPBG (trophoblast glycoprotein). Pregnant rats were injected with TPBG-carrying adenovirus to detect preeclamptic features. HTR-8/SVneo cells transfected with a TPBG overexpression lentiviral vector were used in cell function experiments. The downstream molecular mechanisms of TPBG were explored using RNA sequencing and single-cell RNA sequencing data. TPBG expression was knocked down in the lipopolysaccharide-induced preeclampsia-like rat model to rescue the preeclampsia features. We also assessed TPBG's potential as an early preeclampsia predictor using clinical plasma samples. RESULTS: TPBG emerged as a crucial differentially expressed gene, expressed specifically in syncytiotrophoblasts and extravillous trophoblasts. Subsequently, we established a rat model with preeclampsia-like phenotypes by intravenously injecting TPBG-expressing adenoviruses, observing impaired spiral arterial remodeling, thus indicating a causal correlation between TPBG overexpression and preeclampsia. Studies with HTR-8/SVneo cells, chorionic villous explants, and transwell assays showed TPBG overexpression disrupts trophoblast/extravillous trophoblast migration/invasion and chemotaxis. Notably, TPBG knockdown alleviated the lipopolysaccharide-induced preeclampsia-like rat model. We enhanced preeclampsia risk prediction in early gestation by combining TPBG expression with established clinical predictors. CONCLUSIONS: These findings are the first to show that TPBG overexpression contributes to preeclampsia development by affecting uterine spiral artery remodeling. We propose TPBG levels in maternal blood as a predictor of preeclampsia risk. The proposed mechanism by which TPBG overexpression contributes to the occurrence of preeclampsia via its disruptive effect on trophoblast and extravillous trophoblast migration/invasion on uterine spiral artery remodeling, thereby increasing the risk of preeclampsia.

Dual-layer conduit containing VEGF-A - Transfected Schwann cells promotes peripheral nerve regeneration via angiogenesis.

Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. STATEMENT OF SIGNIFICANCE: Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.

Proteomic scrutiny of nasal microbiomes: implications for the clinic.

INTRODUCTION: The nasal cavity is the initial site of the human respiratory tract and is one of the habitats where microorganisms colonize. The findings from a growing number of studies have shown that the nasal microbiome is an important factor for human disease and health. 16S rRNA sequencing and metagenomic next-generation sequencing (mNGS) are the most commonly used means of microbiome evaluation. Among them, 16S rRNA sequencing is the primary method used in previous studies of nasal microbiomes. However, neither 16S rRNA sequencing nor mNGS can be used to analyze the genes specifically expressed by nasal microorganisms and their functions. This problem can be addressed by proteomic analysis of the nasal microbiome. AREAS COVERED: In this review, we summarize current advances in research on the nasal microbiome, introduce the methods for proteomic evaluation of the nasal microbiome, and focus on the important roles of proteomic evaluation of the nasal microbiome in the diagnosis and treatment of related diseases. EXPERT OPINION: The detection method for microbiome-expressed proteins is known as metaproteomics. Metaproteomic analysis can help us dig deeper into the nasal microbiomes and provide new targets and ideas for clinical diagnosis and treatment of many nasal dysbiosis-related diseases.

Bioinformatics analysis identifies potential autophagy key genes and immune infiltration in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a disease that seriously threatens maternal and fetal health. Appropriate autophagy can shield the placenta from oxidative stress, but its role in PE is unclear. OBJECTIVE: To identify potential autophagy-related genes in PE. METHODS: Microarray datasets from the Gene Expression Omnibus database, compassing the test dataset GSE10588, along with validation datasets GSE4707 and GSE60438 GPL10558, were utilized. Differentially expressed genes (DEGs) were identified using the limma R package, intersected with autophagy-related genes. Hub genes were obtained using the Cytoscape software and analyzed via gene set enrichment analysis (GSEA). The diagnostic capability of hub genes was evaluated using receiver operating characteristic (ROC) curve analysis. Analysis of immune cell infiltration was conducted using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT methods. Placental tissues were collected from 10 normal pregnant women and 10 preeclamptic pregnant women, and the expression of hub genes was validated through immunohistochemistry and western blot analysis. RESULTS: Analysis of the microarray data identified 2224 DEGs, among which 26 were autophagy-related DEGs identified through intersection with autophagy genes. Ten hub genes were identified. Immune cell infiltration analysis suggested the potential involvement of T regulatory cells (Tregs), natural killer cells, neutrophils, and T follicular helper cells in the pathogenesis of PE. ROC curve analysis indicated promising diagnostic capabilities for EGFR and TP53. Additionally, levels of EGFR and TP53 were significantly higher in placental tissue from PE pregnancies compared to normal pregnancies. CONCLUSION: EGFR and TP53 may play a role in PE by influencing autophagy.

Association between serum uric acid/high-density lipoprotein cholesterol ratio and hypertension among reproductive-aged women.

BACKGROUND: Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear. METHODS: In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20-44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P < 0.05 was considered statistically significant. RESULTS: There was significant difference in UHR between the women with and without hypertension (P < 0.001). After adjusting for several covariates, UHR was positively correlated with hypertension (OR > 1, P < 0.001). In the subgroup analysis, the positive correlations still remained between UHR and hypertension in women with various age and those with BMI ≥ 30 kg/m2 (P < 0.05) excepted for adjusting for all covariates. We further found an inflection point of the threshold effect for UHR, and the prevalence of hypertension showed different increased trends below and above the threshold. CONCLUSION: This study indicated a positive association between serum UHR and hypertension among reproductive-aged women, indicating that UHR is a potential clinical marker of hypertension in women.

ATM participates in fine particulate matter-induced airway inflammation through regulating DNA damage and DNA damage response.

The relationship between fine particulate matter (PM2.5) and chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease and asthma, have garnered public attention, while the detailed mechanisms of PM2.5-induced airway inflammation remain unclear. This study reveals that PM2.5 induces airway inflammation both in vivo and in vitro, and, moreover, identifies DNA damage and DNA damage repair (DDR) as results of this exposure. Ataxia telangiectasia-mutated heterozygous (ATM+/- ) and wild-type C57BL/6 (WT) mice were exposed to PM2.5. The results show that, following exposure to PM2.5, the number of neutrophils in broncho alveolar lavage fluid and the mRNA expression of CXCL-1 in lung tissues of the ATM+/- mice were lower than those of the WT mice. The mRNA expression of FANCD2 and FANCI were also down-regulated. Human bronchial epithelial (HBE) cells were transfected with ATM-siRNA to induce down-regulation of ATM gene expression and were subsequently stimulated with PM2.5. The results show that the mRNA expression of TNF-α decreased in the ATM-siRNA-transfected cells. The mRNA expression of CXCL-1 and CXCL-2 in peritoneal macrophages, derived from ATM-null mice in which experiments showed that the protein expression of FANCD2 and FANCI decreased, were also decreased after PM2.5 exposure in ATM-siRNA-transfected HBE cells. In conclusion, PM2.5-induced airway inflammation is alleviated in ATM+/- mice compared with WT mice. ATM promotes PM2.5-induced airway inflammation, which may be attributed to the regulation of DNA damage and DDR.

Association between serum iron and liver transaminases based on a large adult women population.

BACKGROUND: Studies are being focused on the potential roles of iron in various diseases, but remain unclear for the association between serum iron and liver injury, especially in adult women. METHODS: Based on the National Health and Nutrition Examination Survey, we investigated the relationship between serum iron and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among 19,185 adult women. RESULTS: Using weighted multivariate regression analyses, subgroup analyses, and threshold effect analyses, we found that serum iron was independently and positively correlated with ALT and AST. These associations differed in various age or race. Additionally, we found turning points in the curves of the relationship between serum iron and ALT in all women and the non-pregnant women. Using sensitivity analyses, we further found that the associations between serum iron and the liver transaminases remained positive in the non-pregnant women after adjusting for various covariates, but not in pregnant women. Besides, the positive associations between them kept present after excluding the women with high blood pressure, diabetes, and chronic kidney disease. CONCLUSION: The present study indicated a positive association between serum iron and liver transaminases, indicating that serum iron may be a potential biomarker of liver function.

Bioinformatics identification of ferroptosis-related genes and therapeutic drugs in rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic immune disease characterized by synovial inflammation and bone destruction, with a largely unclear etiology. Evidence has indicated that ferroptosis may play an increasingly important role in the onset and development of RA. However, ferroptosis-related genes are still largely unexplored in RA. Therefore, this work focused on identifying and validating the potential ferroptosis-related genes involved in RA through bioinformatics analysis. Methods: We screened differentially expressed ferroptosis-related genes (DEFGs) between RA patients and healthy individuals based on GSE55235 dataset. Subsequently, correlation analysis, protein-protein interaction (PPI) network analysis, GO, and KEGG enrichment analyses were performed using these DEFGs. Finally, our results were validated by GSE12021 dataset. Results: We discovered 34 potential DEFGs in RA based on bioinformatics analysis. According to functional enrichment analysis, these genes were mainly enriched in HIF-1 signaling pathway, FoxO signaling pathway, and Ferroptosis pathway. Four genes (GABARPL1, DUSP1, JUN, and MAPK8) were validated to be downregulated by GSE12021 dataset and were diagnostic biomarkers and therapeutic targets for RA via the regulation of ferroptosis. Discussion: Our results help shed more light on the pathogenesis of RA. Ferroptosis-related genes in RA are valuable diagnostic biomarkers and they will be exploited clinically as therapeutic targets in the future.

Double-to-Single Umbilical Artery With a Low Pulsatility Index Leading to Fetal Death: A Case Report and Review of Literature.

Single umbilical artery (SUA) may be associated with adverse pregnancy outcomes, such as fetal death, emergency cesarean section, premature delivery, small-for-gestational-age infants, and admission to neonatal intensive care unit, and some SUAs are transformed from originally double umbilical arteries (UA). The pulsatility index (PI) can reflect the resistance of UA, and clinicians attach importance to high PI but easily overlook low levels of it. We reported one case of a pregnant woman who underwent double to single UA accompanied by low UA-PI and finally had intrauterine fetal death. Additionally, the literature regarding SUA and UA-PI is reviewed. This study aims to alert clinicians to the risk of double-to-single UA with low UA-PI and strengthen fetal monitoring and timely intervention. We look forward to more clinical evidence to investigate it.

A Retrospective Evaluation of Pregnancy Outcomes Following Bariatric Surgery: A Single-Center Experience.

Background: Bariatric and metabolic surgery (BMS) is an effective treatment for obesity and its complications, but its effect on pregnancy outcomes is inconclusive. The present study aimed to investigate women's pregnancy status and outcomes as well as the impact of pregnancy intervals after BMS. Methods: The menstrual cycle and fertility status of women who underwent BMS in our centre between July 2010 and January 2021 were retrospectively analyzed and followed up until one-year post-delivery. The pregnancy outcomes after BMS were observed, including changes in weight, pregnancy interval, pregnancy complications, weight and health status of the newborn (premature birth, admission to neonatology, or deformity). Results: We identified 31 women who were successfully conceived after BMS. There were statistical differences in weight and menstrual status before and post-operation (P < 0.05), and 77.97% of them had remission or recovery of obesity-related comorbidities. Eighteen patients delivered successfully after BMS, but there were still 12 cases of spontaneous abortion and 1 case of induced abortion. The abortion rate in pregnancy intervals less than 2 years was higher than those ≥2 years (P = 0.045). Of the women who delivered successfully, 5 had pregnancy-specific complications, including gestational diabetes mellitus and hypertensive disorder of pregnancy. However, the growth and development of the newborn are normal since the birth follow-up. Conclusion: The present results suggest that the abortion rate in pregnancy intervals less than 2 years was higher than those ≥2 years. It is recommended that postoperative patients avoid pregnancy until their weight is stable to reduce the risk of adverse pregnancy outcomes.

Risk prediction models of gestational diabetes mellitus before 16 gestational weeks.

BACKGROUND: Gestational diabetes mellitus (GDM) can lead to adverse maternal and fetal outcomes, and early prevention is particularly important for their health, but there is no widely accepted approach to predict it in the early pregnancy. The aim of the present study is to build and evaluate predictive models for GDM using routine indexes, including maternal clinical characteristics and laboratory biomarkers, before 16 gestational weeks. METHODS: A total of 2895 pregnant women were recruited and maternal clinical characteristics and laboratory biomarkers before 16 weeks of gestation were collected from two hospitals. All participants were randomly stratified into the training cohort and the internal validation cohort by the ratio of 7:3. Using multivariable logistic regression analysis, two nomogram models, including a basic model and an extended model, were built. The discrimination, calibration, and clinical validity were used to evaluate the models in the internal validation cohort. RESULTS: The area under the receiver operating characteristic curve of the basic and the extended model was 0.736 and 0.756 in the training cohort, and was 0.736 and 0.763 in the validation cohort, respectively. The calibration curve analysis showed that the predicted values of the two models were not significantly different from the actual observations (p = 0.289 and 0.636 in the training cohort, p = 0.684 and 0.635 in the internal validation cohort, respectively). The decision-curve analysis showed a good clinical application value of the models. CONCLUSIONS: The present study built simple and effective models, indicating that routine clinical and laboratory parameters can be used to predict the risk of GDM in the early pregnancy, and providing a novel reference for studying the prediction of GDM.

Ferritin light chain deficiency-induced ferroptosis is involved in preeclampsia pathophysiology by disturbing uterine spiral artery remodelling.

The proteomic analysis from samples of patients with preeclampsia (PE) displayed a low level of ferritin light chains (FTL), but we do not know what the significance of reduced FTL in PE pathophysiology is. To address this question, we first demonstrated that FTL was expressed in first- and third-trimester cytotrophoblasts, including extravillous trophoblasts (EVTs), of the human placenta. Furthermore, a pregnant rat model of FTL knockdown was successfully established by intravenously injecting adenoviruses expressing shRNA targeting FTL. In pregnant rats with downregulated FTL, we observed PE-like phenotypes and impaired spiral arterial remodelling, implying a causal relationship between FTL downregulation and PE. Blocking ferroptosis with ferrostatin-1 (Fer-1) significantly rescued the above PE-like phenotypes in pregnant rats with FTL knockdown. Furthermore, using trophoblast cell line and chorionic villous explant culture assays, we showed that FTL downregulation induced cell death, especially ferroptosis, resulting in defective uterine spiral artery remodelling. Eventually, this conclusion from the animal model was verified in PE patients' placental tissues. Taken together, this study revealed for the first time that FTL reduction during pregnancy triggered ferroptosis and then caused defective uterine spiral artery remodelling, thereby leading to PE.

Diagnostic signature and immune characteristic of aging-related genes from placentas in Preeclampsia.

INTRODUCTION: Preeclampsia (PE) is a serious pregnancy syndrome. Advanced maternal age (≥ 35 years old) is one of the major risk factors of PE and placental aging is considered to be related to this disease. However, the mechanisms underlying these phenomena remain obscured. METHODS: Gene expression profiles of PE and non-PE placental samples were curated from the GSE75010 dataset. A diagnostic model was constructed and immune characteristics of PE subtypes were estimated. RESULTS: A total of 58 aging-related genes, which may be associated with PE, were identified. Among them, LEP and FLT1 may be key aging-related genes. Based on 5 top genes (PIK3CB, FLT1, LEP, PIK3R1, CSNK1E), a diagnostic nomogram for PE was built (AUC = 0.872 in the GSE75010 dataset). Three molecular subtypes were clustered, which had different immune and angiogenesis characteristics. CONCLUSION: The present study suggests the potential implications of aging-related genes in diagnosing PE. Diverse immune characteristics may be involved in the placental aging of PE.

In vitro study of decellularized rat tissues for nerve regeneration.

Peripheral nerve injuries cause an absence or destruction of nerves. Decellularized nerves, acting as a replacement for autografts, have been investigated in the promotion of nerve repair and regeneration, always being incorporated with stem cells or growth factors. However, such a strategy is limited by size availability. The potential application in heterotopic transplantation of other decellularized tissues needs to be further explored. In this study, rat decellularized kidney (dK) was selected to be compared with decellularized peripheral nerve (dN), since dK has aboundant ECM components and growth factors. The PC-12 cells were cultured on dK and dN scaffolds, as shown in the similar behaviors of cell metabolism and viability, but have a more regular arrangement on dN compared to dK, indicating that the natural structure plays an important role in guiding cell extension. However, we found significant upregulation of axon-growth-associated genes and proteins of PC-12 cells in the dK group compared to the dN group by qRT-PCR, immunofluorescence, and western blotting. Furthermore, various neurotrophic factors and growth factors of acellular kidney and nerve were evaluated by ELISA assay. The lower expression of neurotrophic factors but higher expression of growth factors such as VEGF and HGF from dK suggests that axon growth and extension for PC-12 cells may be partially mediated by VEGF and HGF expression from decellularized kidney, which further points to a potential application in nerve repair and regeneration.

Plasma Olink Proteomics Identifies CCL20 as a Novel Predictive and Diagnostic Inflammatory Marker for Preeclampsia.

Inflammation is generally thought to be involved in the occurrence and development of preeclampsia (PE), but its specific effect on PE remains unclear. In the present study, the expression levels of 92 inflammation-related proteins were measured in the late pregnancy maternal plasma from patients with PE (n = 15) and normal pregnant controls (n = 15) using the Olink inflammation panel based on the highly sensitive and specific proximity extension assay technology. A total of 28 inflammation-related markers differed between the PE and control groups. Among them, fibroblast growth factor 21 (FGF-21) and cysteine-cysteine motif chemokine ligand 20 (CCL20) had the largest fold changes. We further validated the levels of CCL20 in the late (43 with PE and 44 controls) and early (37 with PE and 37 controls) pregnancy maternal plasma using enzyme-linked immunosorbent assay (ELISA). To the best of our knowledge, for the first time, CCL20 was found to be upregulated in the late and early pregnancy plasma of patients with PE and had an area under the curve (AUC) of 0.753 and 0.668, respectively. In conclusion, patients with PE had increased levels of most inflammatory markers, and CCL20 might be a novel potential predictive and diagnostic biomarker for PE.

The association between serum ferritin and blood pressure in adult women: a large cross-sectional study.

BACKGROUND: Studies on the relationships between ferritin and blood pressure remain limited, especially in adult women. The aim of the present study was to investigate the associations between serum ferritin and blood pressure among adult women. METHODS: Using the National Health and Nutrition Examination Survey, a cross-sectional study, including 5521 adult women, was performed. Weighted multivariate regressions, subgroup analyses, threshold effect analyses, and sensitivity analysis were used. RESULTS: The authors found that serum ferritin was independently and positively correlated to diastolic blood pressure (DBP), and this positive correlation kept present among women who are 26-30 years old, non-pregnant women, Mexican American women, and women of other races in the subgroup analyses. Additionally, no significant association was found between serum ferritin and systolic blood pressure (SBP), except in women aged 26-30, Mexican American women, and women of other races. In pregnant women, the association between serum ferritin and SBP was an inverted U-shaped curve with an inflection point at 39.5 ng/mL. CONCLUSIONS: The authors demonstrated that serum ferritin was positively correlated to DBP in adult women, which may provide a novel reference for clinical management.

WASF2 Serves as a Potential Biomarker and Therapeutic Target in Ovarian Cancer: A Pan-Cancer Analysis.

Background: Wiskott-Aldrich syndrome protein family member 2 (WASF2) has been shown to play an important role in many types of cancer. Therefore, it is worthwhile to further study expression profile of WASF2 in human cancer, which provides new molecular clues about the pathogenesis of ovarian cancer. Methods: We used a series of bioinformatics methods to comprehensively analyze the relationship between WASF2 and prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and tried to find the potential biological processes of WASF2 in ovarian cancer. Biological behaviors of ovarian cancer cells were investigated through CCK8 assay, scratch test and transwell assay. We also compared WASF2 expression between epithelial ovarian cancer tissues and normal ovarian tissues by using immunohistochemical staining. Results: In the present study, we found that WASF2 was abnormally expressed across the diverse cancer and significantly correlated with overall survival (OS) and progression-free interval (PFI). More importantly, the WASF2 expression level also significantly related to the TME. Our results also showed that the expression of WASF2 was closely related to immune infiltration and immune-related genes. In addition, WASF2 expression was associated with TMB, MSI, and antitumor drugs sensitivity across various cancer types. Functional bioinformatics analysis demonstrated that the WASF2 might be involved in several signaling pathways and biological processes of ovarian cancer. A risk factor model was found to be predictive for OS in ovarian cancer based on the expression of WASF2. Moreover, in vitro experiments, it was demonstrated that the proliferative, migratory and invasive capacity of ovarian cancer cells was significantly inhibited due to WASF2 knockdown. Finally, the immunohistochemistry data confirmed that WASF2 were highly expressed in ovarian cancer. Conclusions: Our study demonstrated that WASF2 expression was associated with a poor prognosis and may be involved in the development of ovarian cancer, which might be explored as a potential prognostic marker and new targeted treatments.

Placental and plasma early predictive biomarkers for gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) is a common disease that can give rise to adverse obstetric outcomes. For successful early intervention, more studies on novel predictive biomarkers for GDM are required. EXPERIMENTAL DESIGN: The protein expression profiles of placental tissue from patients with GDM and normal pregnant women were investigated using data-independent acquisition proteomics with five biological replicates. Early pregnancy maternal plasma samples from the GDM (n = 79) and control (n = 81) groups were used for further validation of candidate biomarkers. RESULTS: We identified 37 differentially expressed proteins between the two groups. CD109 antigen (CD109) and endosialin (CD248) were identified as hub proteins. In the validation experiments, CD109 expression was lower in the early pregnancy maternal plasma of patients with GDM compared with that in normal pregnant women, and CD248 expression was higher in the GDM group. The area under the curve of CD109, CD248, and their combination as indicators in early pregnancy maternal plasma was 0.681, 0.609, and 0.695, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The present study is the first to obtain preliminary evidence that CD109 and CD248 can predict GDM during early pregnancy, as well as providing proteome-level insights into this disease's pathological mechanisms.