RESUMEN
BACKGROUND: Pre-eclampsia (PE) is a common condition in pregnancy; however, methods for early diagnosis and effective treatment options are lacking. Ferroptosis is a newly identified iron-dependent cell death pathway. The aim of this study was to investigate the role of ferroptosis-related genes in PE, the underlying mechanism, and their potential diagnostic value using a bioinformatics approach. METHODS: We downloaded the GSE48424 and GSE98224 datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PE and healthy pregnancy samples were identified in the GSE48424 dataset and subjected to weighted gene co-expression network analysis; the most relevant modules were intersected with known ferroptosis-related genes to distinctly identify the role of ferroptosis in PE. We further searched transcription factors and microRNAs that are predicted to regulate these ferroptosis-related genes, and patients in the GSE48424 dataset were divided into two groups according to high or low expression of the key ferroptosis-related genes associated with PE. To obtain robust key ferroptosis-related genes in PE, we validated their expression levels in the external dataset GSE98224. Finally, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was utilized to access the expression of these genes in the PE and normal blood samples. RESULTS: Six ferroptosis-related genes involved in PE were obtained by overlapping 3661 genes most associated with PE, 565 DEGs between PE and normal samples, and 259 known ferroptosis-related genes. Among these genes, patients with PE displaying lower expression levels of NOS2 and higher expression levels of PTGS2 had a higher ferroptosis potential index. The expression pattern of NOS2 was consistent in the GSE48424 and GSE98224 datasets. RT-qPCR data confirmed that NOS2 expression was more significantly elevated in patients with PE than in those with a normal pregnancy. CONCLUSIONS: Our study explored the diagnostic value of ferroptosis-related genes in PE, and identified NOS2 as the key gene linking ferroptosis and PE, suggesting a new candidate biomarker for early PE diagnosis.
Asunto(s)
Ferroptosis , Óxido Nítrico Sintasa de Tipo II , Preeclampsia , Femenino , Humanos , Embarazo , Biomarcadores , Biología Computacional , Óxido Nítrico Sintasa de Tipo II/genética , Preeclampsia/diagnóstico , Preeclampsia/genéticaRESUMEN
INTRODUCTION: Accelerated senescence of trophoblast may cause several diverse pregnancy outcomes; however, the cause of accelerated trophoblast senescence remains unclear. The renin-angiotensin system (RAS) is closely related to organ senescence. Therefore, in the present study, we hypothesized that angiotensin (Ang)II, one of the most important RAS family members, accelerates trophoblast senescence through the transforming growth factor ß-1 (TGF-ß1) pathway. METHODS: AngII and Ang1-7 were used to stimulate pregnant rats. AngII and its inhibitor olmesartan were used to stimulate trophoblast. Thereafter, senescence levels were measured. Furthermore, we used AngII to stimulate trophoblast and utilized RNA-sequencing (RNAseq) to analyze the expression of differentially expressed genes (DEGs). After identifying the overlapping genes by comparing the DEGs and senescence-related genes, we employed CytoHubba software to calculate the top five hub genes and selected TGF-ß1 as the target gene. We transfected the AngII-stimulated trophoblast with TGF-ß1 small interfering RNA (siRNA) and measured the senescence levels. RESULTS: Senescence markers were upregulated in the AngII group compared with that in the control group. Furthermore, following AngII stimulation and RNAseq measurement, we identified 607 DEGs and 13 overlapping genes. The top five hub genes were as follows: PLAU, PTGS2, PDGF-ß, TGF-ß1, and FOXO3. Upon knockdown of TGF-ß1 expression in AngII-stimulated trophoblast using TGF-ß1 siRNA, we observed a downregulation of p53 and p62 mRNA expression. DISCUSSION: AngII accelerates trophoblast senescence through the TGF-ß1 pathway.
Asunto(s)
Angiotensina II , Senescencia Celular , Factor de Crecimiento Transformador beta1 , Trofoblastos , Animales , Femenino , Embarazo , Ratas , Angiotensina II/metabolismo , Biología Computacional/métodos , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Trofoblastos/citología , Trofoblastos/metabolismoRESUMEN
Backgrounds: Frailty is a significant problem for older persons since it is linked to a number of unfavorable consequences. According to observational researches, air pollution may raise the risk of frailty. We investigated the causal association between frailty and air pollution (including PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides) using Mendelian randomization approach. Methods: We conducted MR analysis using extensive publically accessible GWAS (genome-wide association studies) summary data. The inverse variance weighted (IVW) method was employed as the primary analysis method. The weighted median model, MR-Egger, simple model, and weighted model approaches were chosen for quality control. The Cochran's Q test was utilized to evaluate heterogeneity. Pleiotropy is found using the MR-Egger regression test. The MR-PRESSO method was used to recognize outliers. The leave-one-out strategy was used to conduct the sensitivity analysis. Results: MR results suggested that PM2.5 was statistically significantly associated with frailty [odds ratio (OR) = 1.33; 95%confidence interval (CI) = 1.12-1.58, p = 0.001] in IVW method. We observed no statistical association between PM2.5-10(OR = 1.00, 95% CI = 0.79-1.28, p = 0.979), PM10(OR = 0.91, 95% CI = 0.75-1.11, p = 0.364), nitrogen dioxide (OR = 0.98, 95% CI = 0.85-1.12, p = 0.730), nitrogen oxides (OR = 1.15, 95% CI = 0.98-1.36, p = 0.086) and frailty. There was no pleiotropy in the results. The sensitivity analysis based on the leave-one-out method showed that the individual single nucleotide polymorphisms (SNPs) did not affect the robustness of the results. Conclusion: The current MR investigation shows a causal association between PM2.5 and frailty. Frailty's detrimental progression may be slowed down with the help of air pollution prevention and control.
Asunto(s)
Contaminación del Aire , Fragilidad , Humanos , Anciano , Anciano de 80 o más Años , Dióxido de Nitrógeno/efectos adversos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Contaminación del Aire/efectos adversos , Material Particulado/efectos adversosRESUMEN
Objective: Since 2022, Omicron has been circulating in China as a major variant of the novel coronavirus, but the effects of infection with Omicron variants on pregnant women and newborns are unknown. The purpose of this study was to determine the clinical characteristics of Omicron infection during pregnancy and its effect on pregnancy outcomes. Methods: This study retrospectively analyzed the data of 93 confirmed cases of novel coronavirus infection and 109 non-infected patients admitted to the isolation ward of Guangdong Maternal and Child Health Hospital from December 1, 2022 to January 31, 2023, and statistically analyzed the clinical features of Omicron variant infection during pregnancy and its impact on pregnancy outcomes. Further effects of underlying diseases on Omicron infection in pregnant women were analyzed. Results: The incubation period of COVID-19 infection was 0.99±0.86 days, 94.38% of patients had fever or other respiratory symptoms, the lymphocyte count in the infected group was lower than that in the uninfected group, and the lymphocyte count was further reduced in the patients with pregnancy complications or complications. Compared with the uninfected group, APTT and PT were prolonged, platelet count and fibrinogen were decreased in the infected group, all of which had statistical significance. COVID-19 infection during pregnancy increased the rate of cesarean section compared to uninfected pregnant patients, and COVID-19 infection in gestational diabetes resulted in a 4.19-fold increase in cesarean section rate. There was no statistically significant difference in gestational age between the two groups. The incidence of intrauterine distress, turbidity of amniotic fluid and neonatal respiratory distress were higher in the infection group. No positive cases of neonatal COVID-19 infection have been found. Conclusion: The patients infected with omicron during pregnancy often have febrile respiratory symptoms with lymphocyopenia, but the incidence of severe disease is low. Both Omicron infection and gestational diabetes further increase the incidence of cesarean section, and this study found no evidence of vertical transmission of Omicron.
RESUMEN
Introduction: Placental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method. Methods: After obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The "ClusterProfiler" R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes. Results: We found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1ß (IL-1ß) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below -5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2. Conclusions: GROA, IL-1ß, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.
Asunto(s)
Aborto Espontáneo , Hipertensión , Nacimiento Prematuro , Recién Nacido , Embarazo , Humanos , Femenino , Interleucina-10 , Interleucina-18 , Interleucina-9 , Simulación del Acoplamiento Molecular , Medicina Tradicional China , Análisis de la Aleatorización Mendeliana , Nacimiento Prematuro/genética , PlacentaRESUMEN
Background: Preeclampsia (PE), which has a high incidence rate worldwide, is a potentially dangerous syndrome to pregnant women and newborns. However, the exact mechanism of its pathogenesis is still unclear. In this study, we used bioinformatics analysis to identify hub genes, establish a logistic model, and study immune cell infiltration to clarify the physiopathogenesis of PE. Methods: We downloaded the GSE75010 and GSE10588 datasets from the GEO database and performed weighted gene coexpression network analysis (WGCNA) as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The online search tool for the retrieval of interacting genes and Cytoscape software were used to identify hub genes, which were then used to establish a logistic model. We also analyzed immune cell infiltration. Finally, we verified the expression of the genes included in the predictive model via RT-PCR. Results: A total of 100 and 212 differently expressed genes were identified in the GSE75010 and GSE10588 datasets, respectively, and after overlapping with WGCNA results, 17 genes were identified. KEGG and GO analyses further indicated the involvement of these genes in bioprocesses, such as gonadotropin secretion, immune cell infiltration, and the SMAD and MAPK pathways. Additionally, protein-protein interaction network analysis identified 10 hub genes, six (FLT1, FLNB, FSTL3, INHA, TREM1, and SLCO4A1) of which were used to establish a logistic model for PE. RT-PCR analysis also confirmed that, except FSTL3, these genes were upregulated in PE. Our results also indicated that macrophages played the most important role in immune cell infiltration in PE. Conclusion: This study identified 10 hub genes in PE and used 6 of them to establish a logistic model and also analyzed immune cell infiltration. These findings may enhance the understanding of PE and enable the identification of potential therapeutic targets for PE.
Asunto(s)
Proteínas Relacionadas con la Folistatina , Preeclampsia , Biomarcadores de Tumor/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Femenino , Proteínas Relacionadas con la Folistatina/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Humanos , Recién Nacido , Preeclampsia/genética , EmbarazoRESUMEN
OBJECTIVE: To evaluate the effect of time elapsed on continuous pulse contour cardiac output (PCCO) measurement in septic shock patients. METHODS: Data during February 2011 to February 2013 from 25 septic shock patients equipped with a pulse indicator continuous cardiac output (PiCCO) device in Department of Critical Care Medicine of Guangzhou Medical University were retrospectively analyzed. PCCO was recorded immediately before transpulmonary thermodilution (COTPTD) calibration. After divided by ideal body surface area, cardiac index (CI) was calculated, and PCCI/CITPTD pairs were analyzed. Four subsets of CI pairs were defined according to intervals of time elapsed from the previous calibration [within the first hour (including 1 hour), between 1 and 8 hours (including 8 hours), between 8 and 16 hours (including 16 hours), and more than 16 hours]. Linear regression, the threshold value of concordance (as indicated by bias ± 2SD) and percentage error (2SD/the mean of CITPTD) were used to compare agreement between PCCI and CITPTD. RESULTS: A total of 162 data pairs from 25 patients were analyzed. For all data pairs, PCCI correlated significantly with CITPTD (r² = 0.494, P<0.001), the bias±2SD was -(0.06 ± 1.41) L × min⻹ × m⻲ and the percentage error was 37%. Among the four time-interval subsets, the percentage error was <30% only in subset between 1 and 8 hours, and the percentage error in other subsets was over 30%. Linear regression analysis between ΔPCCI and ΔCITPTD showed a r² of 0.217 (P<0.001) for the whole 162 data pairs. A r² of 0.327 (P<0.001) and a r² of 0.303 (P<0.001) were calculated for the subset of between 1 and 8 hours and between 8 and 16 hours respectively. CONCLUSIONS: Our study in septic shock patients suggests that the accuracy of PCCO will be decreased as the increase of the time interval for calibration. Transpulmonary thermodilution calibration should be performed again if hemodynamic changes or was inconsistent with the clinical presentation. It is suggested that re-calibration should be done within 8 hours.