RESUMO
BACKGROUND Severe pre-eclampsia (sPE) and postpartum hemorrhage (PPH) in pregnancy have serious impact on maternal and fetal health and life. Co-occurrence of sPE and PPH often leads to poor pregnancy outcomes. We explored risk factors associated with PPH in women with sPE. MATERIAL AND METHODS This retrospective study included 1953 women with sPE who delivered at the Women's Hospital of Nanjing Medical University between April 2015 and April 2023. Risk factors for developing PPH in sPE were analyzed, and subgroups were analyzed by delivery mode (cesarean and vaginal). RESULTS A total of 197 women with PPH and 1756 women without PPH were included. Binary logistic regression results showed twin pregnancy (P<0.001), placenta accreta spectrum disorders (P=0.045), and placenta previa (P<0.001) were independent risk factors for PPH in women with sPE. Subgroup analysis showed risk factors for PPH in cesarean delivery group were the same as in the total population, but vaginal delivery did not reduce risk of PPH. Spinal anesthesia reduced risk of PPH relative to general anesthesia (P=0.034). Vaginal delivery group had no independent risk factors for PPH; however, magnesium sulfate (P=0.041) reduced PPH incidence. CONCLUSIONS Women with twin pregnancy, placenta accreta spectrum disorders, placenta previa, and assisted reproduction with sPE should be alerted to the risk of PPH, and spinal anesthesia should be preferred in cesarean delivery. Magnesium sulfate should be used aggressively in women with sPE; however, the relationship between magnesium sulfate and PPH risk needs further investigation.
Assuntos
Cesárea , Placenta Prévia , Hemorragia Pós-Parto , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Fatores de Risco , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/epidemiologia , Estudos Retrospectivos , Adulto , Pré-Eclâmpsia/epidemiologia , Cesárea/efeitos adversos , China/epidemiologia , Placenta Prévia/epidemiologia , Parto Obstétrico/efeitos adversos , Parto Obstétrico/métodos , Gravidez de Gêmeos , Placenta Acreta/epidemiologia , Resultado da Gravidez , Modelos Logísticos , IncidênciaRESUMO
BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.
Assuntos
Aspirina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Adulto , China , Feminino , Humanos , Incidência , Pré-Eclâmpsia/epidemiologia , Gravidez , Gravidez de Alto RiscoRESUMO
BACKGROUND: Preterm birth is one of the main causes of perinatal morbidity and mortality and imposes a heavy burden on families and society. The aim of this study was to identify risk factors and analyze birth conditions and complications of newborns born at < 32 gestational weeks for extremely preterm (EP) and very preterm (VP) birth in the clinic to further extend the gestational period. METHODS: We performed a retrospective cohort study and collected data from 1598 pregnant women and 1660 premature newborns (excluding 229 premature babies who died due to severe illness and abandonment) admitted to the Obstetrics and Gynecology Hospital Affiliated with Nanjing Medical University in China from 2016 to 2020. We compared women's and newborns' characteristics by t-tests and Chi-square tests for continuous and categorical variables, respectively. Multivariable logistic regression was performed to estimate the effects of risk factors on EP and VP birth. RESULTS: We identified 3 independent risk factors for EP birth: cervical incompetency (P < 0.001); multiple pregnancy (P < 0.01), primipara (P < 0.001). Additionally, we identified 4 independent risk factors for VP birth: gestational diabetes mellitus (GDM) (P < 0.05), preterm premature rupture of membrane (PPROM) (P < 0.01), fetal intrauterine distress (P < 0.001), and hypertensive disorder complicating pregnancy (HDCP) (P < 0.001). In addition, pairwise comparisons revealed statistically significant differences in the incidence rates of neonatal pneumonia, bronchopulmonary dysplasia (BPD) and sepsis between the 28-28 + 6 and 29-29 + 6 weeks of gestation groups (P < 0.05). Compared with 28-28 + 6 weeks of gestation, neonatal complications were significantly more common at < 26 weeks of gestation (P < 0.05). The incidence rates of neonatal intracranial hemorrhage(NICH), patent ductus arteriosus(PDA), patent foramen ovale(PFO), pneumonia, BPD and sepsis were significantly higher in the 26-26 + 6 and 27-27 + 6 gestational weeks than in the 28-28 + 6 gestational weeks (P < 0.05). CONCLUSION: PPROM, is the most common risk factor for EP and VP birth, and cervical insufficiency, multiple pregnancy, and primipara are independent risk factors for EP birth. Therefore, during pregnancy, attention should be devoted to the risk factors for PPROM, and reproductive tract infection should be actively prevented to reduce the occurrence of PPROM. Identifying the risk factors for cervical insufficiency, actively intervening before pregnancy, and cervical cervix ligation may be considered to reduce the occurrence of EP labor. For iatrogenic preterm birth, the advantages and disadvantages should be carefully weighed, and the gestational period should be extended beyond 28 weeks to enhance the safety of the mother and child and to improve the outcomes of preterm birth.
Assuntos
Displasia Broncopulmonar , Ruptura Prematura de Membranas Fetais , Doenças do Recém-Nascido , Nascimento Prematuro , Sepse , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Displasia Broncopulmonar/epidemiologia , Ruptura Prematura de Membranas Fetais/epidemiologia , Idade Gestacional , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Fatores de Risco , Sepse/epidemiologia , AdultoRESUMO
Recently, a large number of long noncoding RNAs (lncRNAs) have been reported in human diseases that are evolutionarily conserved and are likely to play a role in many biological events including pre-eclampsia. In our previous research, we selected thousands of lncRNAs for their relationship with early-onset pre-eclampsia. Among these lncRNAs, a lncRNA named uc.294 attracted our attention, was once reported to specifically be expressed at a high level in the early-onset of pre-eclampsia. This study aims to investigate the function of uc.294 in early-onset pre-eclampsia and the possible mechanism. The uc.294 expression level in early-onset pre-eclampsia or in normal placenta tissues was evaluated by quantitative real-time polymerase chain reaction. To detect the proliferation, invasion, and apoptosis capacity of the trophoblast cells, we performed the Cell Counting Kit-8 assay, transwell assay, and flow cytometry, respectively. Here we report, for the first time, that uc.294 inhibits proliferation, invasion, and promotes apoptosis of trophoblast cells HTR-8/SVneo by working in key aspects of biological behaviors. However, how uc.294 acts to regulate gene functions in early-onset pre-eclampsia needs further exploration.
Assuntos
Pré-Eclâmpsia , RNA Longo não Codificante/metabolismo , Trofoblastos/citologia , Adulto , Linhagem Celular , Proliferação de Células/fisiologia , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Humanos , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Placenta/metabolismo , Gravidez , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Regulação para CimaRESUMO
Preeclampsia (PE) is a complex disorder that is characterized by hypertension and proteinuria after the 20th week of pregnancy, and it causes most neonatal morbidity and perinatal mortality. Most studies suggest that placental dysfunction is the main cause of PE. However, genetic factors, immune factors, and systemic inflammation are also related to the pathophysiology of this syndrome. Thus far, the exact pathogenesis of PE is not yet fully understood, and intense research efforts are focused on PE to elucidate the pathophysiological mechanisms. MicroRNAs (miRNAs) refer to small single-stranded and noncoding molecules that can negatively regulate gene expression, and miRNA regulatory networks play an important role in diverse pathological processes. Many studies have confirmed deregulated miRNA in pregnant patients with PE, and the function and mechanism of these differentially expressed miRNA are gradually being revealed. In this review, we summarize the current research about miRNA involved in PE, including placenta-specific miRNA, their predictive value, and their function in the development of PE. This review will provide fundamental evidence of miRNA in PE, and further studies are necessary to explore the roles of miRNA in the early diagnosis and treatment of PE.
Assuntos
Pressão Sanguínea , MicroRNAs/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Animais , Pressão Sanguínea/genética , Diagnóstico Precoce , Feminino , Regulação da Expressão Gênica , Marcadores Genéticos , Humanos , MicroRNAs/genética , Placenta/fisiopatologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/terapia , Valor Preditivo dos Testes , Gravidez , Prognóstico , Transdução de SinaisRESUMO
BACKGROUND/AIMS: Early screening and diagnosis is important for minimizing gestational adverse outcomes. Routine screening of gestational diabetes mellitus (GDM) at 24-28 weeks with 75 g oral glucose challenge test (OGCT) leaves limited time for intervention and prevention. This study aims to analyze maternal serum peptides in the early second-trimester for prediction of gestational diabetes mellitus (GDM). METHODS: Serum samples were collected from 16-18-week pregnant women that visited Nanjing Maternity and Child Health Care Hospital from April to August 2015. According to gestational outcome with or without GDM in late pregnancy, 200 of serum samples from GDM mothers and controls were randomly divided into two subgroups. Peptidomic identification of serum peptides was performed by combining ultrafiltration and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the differentially-expressed peptides between two groups. RESULTS: A total of 297 identified peptides, originating from 228 proteins, were significantly differentially expressed in the GDM group compared with control. These precursor proteins may play critical roles in cell death of cortical neurons, elongation of cellular protrusions, and stabilization of microtubules. Major networks identified included those involving lipid metabolism, molecular transport and small molecule biochemistry. CONCLUSION: We provide for the first time a validated peptidome profile of early second-trimester serum in normal and GDM mothers, and we investigated the potential serum biomarkers for GDM. We concluded that 297 peptides could serve as potential biomarkers for GDM.
Assuntos
Diabetes Gestacional/sangue , Peptídeos/sangue , Adulto , Biomarcadores/sangue , Cromatografia Líquida , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Espectrometria de Massas em TandemRESUMO
STUDY QUESTION: What is the role of insulin-like growth factor 2 (IGF2)-derived miR-483-3p in macrosomia? SUMMARY ANSWER: IGF2-derived intronic miR-483-3p is overexpressed in macrosomia placentas, and miR-483-3p prompts HTR-8/SVneo extravillous trophoblast cell line proliferation through down-regulation of its target RB1 inducible coiled-coil 1 (RB1CC1). WHAT IS KNOWN ALREADY: Macrosomia is a common pregnancy-associated disease and causes a number of adverse maternal and perinatal outcomes. The development of macrosomia is reportedly attributable to over proliferation of the placental cells. MicroRNAs (miRNAs) play an important role in the development of fetal and placenta by regulating their target genes. Here, we investigated the role of IGF2-derived intronic miR-483-3p in macrosomia. STUDY DESIGN, SIZE, DURATION: The expression of IGF2, miR-483-3p and its target gene in placental tissues from 30 pregnant women who had macrosomia was compared to those of 30 gestation-matched healthy pregnant controls. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR-8/SVneo cell was used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placenta tissues were collected from pregnant women who had macrosomia without diabetes or other complications (n = 30) and healthy pregnant controls (n = 30). HTR-8/SVneo cells were transfected with specific miRNA mimics or inhibitors. MiRNA and mRNA isolated from placenta tissues or cells were measured by quantitative real-time PCR. Protein was measured by western blot. Cell proliferation was assayed using a colorimetric proliferation assay method. Cell cycle and apoptosis were analyzed by flow cytometry. The putative targets of miR-483-3p were predicted using the TargetScan, miRanda, miRDB and DIANA algorithms. Dual luciferase reporter assay was used to measure the relationship of miR-483-3p and RB1CC1. MAIN RESULTS AND THE ROLE OF CHANCE: IGF2-derived miR-483-3p was overexpressed in macrosomia placentas. miR-483-3p promoted proliferation in HTR-8/SVneo cells and had a positive relationship with its host gene IGF2. Subsequently, RB1CC1 was confirmed as a direct target of miR-483-3p, which may be an important mediator of cell growth regulation for miR-483-3p. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The level of IGF2 and its intronic miR-483-3p in the serum of these participants was not investigated. Further studies are required to understand the mechanisms underlying the cause of the increase of IGF2 and miR-483-3p in macrosomia. WIDER IMPLICATIONS OF THE FINDINGS: These findings give a new insight into the role of intronic miRNA and its host gene in the development of macrosomia. Furthermore, it may offer a new target for prognostic and therapeutic intervention for macrosomia. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by awards from National Natural Science Foundation of China (Nos. 81401213, 81673217, 81703260), Jiangsu Provincial Medical Youth Talent (No. QNRC2016110), Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine), the Education Department of Jiangsu Province (No. 16KJB330010), the Science and Technology Department of Jiangsu Province (No. BK20160227), the China Postdoctoral Science Foundation funded project (No. 2016M601892). The authors declare no competing financial interests.
Assuntos
Macrossomia Fetal/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , MicroRNAs/metabolismo , Proteínas Tirosina Quinases/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismo , Proteínas Relacionadas à Autofagia , Feminino , Macrossomia Fetal/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Humanos , Técnicas In Vitro , Fator de Crescimento Insulin-Like II/genética , MicroRNAs/genética , Placenta/citologia , Gravidez , Primeiro Trimestre da Gravidez , Proteínas Tirosina Quinases/genéticaRESUMO
Preeclampsia is a kind of disease that severely harms the health of pregnant women and infants. To better understand the molecular mechanisms involved in preeclampsia, we used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to construct a comparative peptidomic profiling of human serum between normal and preeclamptic pregnancies. A total of 201 peptides were confidently identified, with 21 up-regulated and three down-regulated. Further analysis indicated that these differentially expressed peptides correlate with enzyme regulator activity, biological regulation, and coagulation cascades occurring during pathological changes of preeclampsia. The identification of key peptides in serum may serve not only as a basis for better understanding and further exploring the etiology and pathogenesis of PE, but also as potential biomarkers and in providing targets for future therapy in PE, especially in early onset severe PE (sPE). J. Cell. Biochem. 118: 4341-4348, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Peptídeos/sangue , Pré-Eclâmpsia/sangue , Proteômica , Adulto , Biomarcadores/sangue , Feminino , Humanos , GravidezRESUMO
BACKGROUND/AIMS: FOXC2 has been reported to play a role in tumor progression, but the correlations of FOXC2 with the cisplatin (CDDP) resistance of ovarian cancer cells are still unclear. The purpose of the present study is to investigate the roles of FOXC2 in the CDDP resistance of ovarian cancer cells and its possible mechanisms. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of FOXC2 mRNA in CDDP-resistant or sensitive ovarian cancer tissues and cell lines (SKOV3/CDDP and SKOV3). Gain- and loss-of-function assays were performed to analyze the effects of FOXC2 knockdown or overexpression on the in vitro and in vivo sensitivity of ovarian cancer cells to CDDP and its possible molecular mechanisms. RESULTS: The relative expression level of FOXC2 mRNA in CDDP-resistant ovarian cancer tissues was higher than that in CDDP-sensitive tissues. Also, the expression of FOXC2 mRNA and protein in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) cell line was higher than that in its parental cell line (SOKV3). Small hairpin RNA (shRNA)-mediated FOXC2 knockdown significantly increased the in vitro and in vive sensitivity of SKOV3/CDDP cells to CDDP by enhancing apoptosis, while upregulation of FOXC2 significantly decreased the in vitro and in vivo sensitivity of SKOV3 cells to CDDP by reducing apoptosis. Furthermore, FOXC2 activates the Akt and MAPK signaling pathways, and then induced the decreased expression of Bcl-2 protein and the increased expression of Bax and cleaved caspase-3 proteins. CONCLUSIONS: FOXC2 mediates the CDDP resistance of ovarian cancer cells by activation of the Akt and MAPK signaling pathways, and may be a potential novel therapeutic target for overcoming CDDP resistance in human ovarian cancer.
Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fatores de Transcrição Forkhead/genética , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND/AIMS: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. METHODS: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. RESULTS: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26µM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3ß signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. CONCLUSIONS: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Colágeno/química , Combinação de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Concentração Inibidora 50 , Laminina/química , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Proteoglicanas/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM). The associations between long non-coding RNAs (lncRNAs) and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. METHOD: Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. RESULT: The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. CONCLUSIONS: Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology.
Assuntos
Diabetes Gestacional/genética , Macrossomia Fetal/genética , Regulação da Expressão Gênica , RNA Longo não Codificante/genética , Adulto , Diabetes Gestacional/sangue , Feminino , Sangue Fetal/metabolismo , Macrossomia Fetal/sangue , Perfilação da Expressão Gênica , Humanos , Gravidez , RNA Longo não Codificante/sangueRESUMO
BACKGROUND/AIMS: Exosomes are extracellular vesicles that are involved in several biological processes. The roles of proteins from human umbilical cord blood exosomes in the pathogenesis of preeclampsia remains poorly understood. METHODS: In this study, we used high-resolution LC-MS/MS technologies to construct a comparative proteomic profiling of human umbilical cord blood exosomes between normal and preeclamptic pregnancies. RESULTS: A total of 221 proteins were detected in human umbilical cord blood exosomes, with 14 upregulated and 15 downregulated proteins were definitively identified between preeclamptic and control pregnancies. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that these differentially expressed proteins correlate with enzyme regulator activity, binding, extracellular region, cell part, biological regulation, cellular process and complement and coagulation cascades occurring during pathological changes of preeclampsia. CONCLUSION: Our results show significantly altered expression profiles of proteins in human umbilical cord blood exosomes between normal and preeclampsia pregnancies. These proteins may be involved in the etiology of preeclampsia.
Assuntos
Exossomos/metabolismo , Sangue Fetal/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Proteômica , Espectrometria de Massas em Tandem/métodos , Adulto , Cromatografia Líquida , Cromossomos Humanos/metabolismo , Biologia Computacional , Feminino , Ontologia Genética , Humanos , Nanopartículas , Pré-Eclâmpsia/patologia , Gravidez , Mapas de Interação de Proteínas , Proteoma/metabolismoRESUMO
BACKGROUND: Fetal growth restriction (FGR) is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. A large body of evidence suggests that FGR may be associated with the placenta, although its etiology and pathogenesis remain to be fully elucidated. METHODS AND RESULTS: To better understand the molecular mechanisms underlying the pathological development of the placenta in FGR, we used tandem mass tags (TMTs) to construct a large-scale comparative proteomic profile of human placentas from normal and FGR pregnancies. A total of 1,198 kinds of proteins were identified in the control and FGR placentas, of which 95 were differentially expressed between two groups. Ingenuity Pathway Analysis (IPA) was used to organize these differentially expressed proteins into networks of interacting proteins and to identify the modules of functionally related proteins. Western blotting was used to verify the expression patterns of several randomly selected proteins. CONCLUSION: The placentas of women with FGR displayed significant proteome differences compared with normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of FGR. Further studies and validations are required to elucidate the exact roles of these proteins in FGR pathogenesis.
Assuntos
Retardo do Crescimento Fetal/metabolismo , Placenta/metabolismo , Proteoma/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Desenvolvimento Fetal/fisiologia , Humanos , Gravidez , Proteômica/métodosRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. METHOD AND RESULTS: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. CONCLUSION: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.
Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , MicroRNAs/sangue , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/genética , Adulto , Apoptose , Ciclo Celular , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Humanos , MicroRNAs/genética , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Adulto JovemRESUMO
Peroxisome proliferator-activated receptor delta (Ppard) activation has been implicated in regulating a multitude of biological processes in placental development. In this study, we employed the UPLC-ESI-TOFMS approach to investigate the metabolic traits in placenta from GW501516-treated mice at Embryonic Day 10.5. By analyzing the mass spectrum data, ions with the most significant differences between control and GW501516-treated groups were identified. Among these metabolites, the fatty acids, phospholipids, and sterol lipids were dramatically increased. Ingenuity Pathway Analysis (IPA) showed that phosphatidylethanolamine biosynthesis and glycolysis were the top two altered metabolic pathways involved in carbohydrate metabolism, energy production, and lipid metabolism. Subsequent immunoblotting experiments provided evidence for positive correlation of PPARD level and AKT and ERK signaling pathways upon GW501516 treatment. Furthermore, the stimulation of GW501516 increased trophoblast cell fusion gene syncytin-A (Syna), but not syncytin-B (Synb), expression, suggesting a potential role of Ppard activation in promoting cytotrophoblast differentiation. Our results reveal that Ppard activation elicits dramatic changes of the metabolic activities in placenta, which is correlated to AKT and ERK signaling.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Metabolismo dos Lipídeos , Placenta/metabolismo , Placentação , Proteínas da Gravidez/metabolismo , Receptores Citoplasmáticos e Nucleares/agonistas , Animais , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Camundongos Transgênicos , Receptores Patched , Fosfatidiletanolaminas/metabolismo , Placenta/citologia , Placenta/efeitos dos fármacos , Placentação/efeitos dos fármacos , Gravidez , Proteínas da Gravidez/agonistas , Proteínas da Gravidez/genética , Proteínas Proto-Oncogênicas c-akt/agonistas , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Tiazóis/farmacologiaRESUMO
AIMS: To investigate the contribution of dysfunction of maternal hemodynamics to renal impairment in preeclampsia (PE). METHODS: Urinary protein excretion, serum creatinine, blood urea nitrogen, uric acid, and glomerular filtration rate were assessed in 571 pregnant women with PE in addition to and noninvasive hemodynamic monitoring. Patients were classified into two groups: PE with renal impairment (glomerular filtration rate <90 ml/min/1.73 m², n = 161) and PE with normal renal function (n = 410). Cut-off values for hemodynamic parameters were calculated using receiver-operating characteristic curve analysis. RESULTS: Maternal systolic function and cardiac output parameters were low and peripheral resistance was high in the PE renal impairment group. Cut-off values for the hemodynamic parameters, cardiac index, cardiac output, systemic vascular resistance index, and systemic vascular resistance were 2.85 l/min/m², 5.25 l/min, 3,014.5 dyn s cmâ»5 m² and 1,636.0 dyn s cmâ»5, respectively, according to receiver-operating characteristics curves. CONCLUSION: Renal impairment in PE is associated with reduced maternal cardiac output and increased peripheral resistance.
Assuntos
Hemodinâmica/fisiologia , Pré-Eclâmpsia/fisiopatologia , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Adulto , Área Sob a Curva , Pressão Sanguínea , Nitrogênio da Ureia Sanguínea , Cardiografia de Impedância , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Frequência Cardíaca , Humanos , Valor Preditivo dos Testes , Gravidez , Proteinúria/urina , Curva ROC , Insuficiência Renal/metabolismo , Volume Sistólico , Ácido Úrico/sangue , Resistência Vascular , Adulto JovemRESUMO
The mechanisms underlying late-onset preeclampsia (LOPE) remain unknown. Metabolic disturbances have been implicated as a primary factor in LOPE development. Lipids have been shown to have great clinical value in recent years. This study aimed to use lipidomics to provide evidence for the etiology and potential therapeutic approaches for LOPE. Twenty patients with LOPE and 20 healthy controls were enrolled in this study. Placental lipidomic data were acquired using liquid chromatographymass spectrometry (LC-MS/MS), and the data were analyzed by weighted gene correlation network analysis (WGCNA) and statistical methods. Of 1508 identified lipids, 226 were differentially expressed between the LOPE and control groups. In the LOPE group, the abundance of most unsaturated triglycerides (TG) increased, whereas that of other lipids, including phosphatidylcholine (PC), sphingomyelin, and phosphatidylserine (PS) increased. The WGCNA implied that the correlation network module of lipids was highly related to clinical traits. Pathway analysis revealed that these dysregulated lipids are closely related to glycerophospholipid metabolism. Lipidomics may help identify the pathogenesis underlying placental dysfunction in LOPE patients and provide potential therapeutic targets in the future.
Assuntos
Placenta , Pré-Eclâmpsia , Humanos , Gravidez , Feminino , Placenta/metabolismo , Lipidômica , Cromatografia Líquida , Pré-Eclâmpsia/metabolismo , Espectrometria de Massas em Tandem , Análise Espectral , Lecitinas/metabolismoRESUMO
OBJECTIVES: To analyze the expression patterns of poly(rC)-binding protein 1 (PCBP1) in complete hydatidiform moles (HMs) and to determine the predictive value of PCBP1 during postmolar follow-up after uterine evacuation. MATERIALS AND METHODS: The PCBP1 protein expression profile was investigated in 10 complete moles that remained benign, 10 complete moles that underwent malignant transformation, and 10 choriocarcinoma tissues using Western blot analysis. The PCBP1 protein expression patterns in complete HM samples gathered from 69 patients were also detected by immunohistochemical analysis. The association of PCBP1 protein expression with the progression in HMs was subsequently assessed. RESULTS: The expression of PCBP1 was significantly lower in malignant-transformed moles than benign moles. The PCBP1 expression level was negatively associated with malignant transformation and serum human chorionic gonadotropin levels. Logistic regression analysis indicated that complete moles with high PCBP1 expression levels had a significantly lower risk of progression to gestational trophoblastic tumors (odds ratio, 0.22; 95% confidence interval, 0.07-0.67). CONCLUSIONS: These observations suggest that PCBP1 may be important in the pathogenesis of gestational trophoblastic tumors. In addition to the ß-fraction of human chorionic gonadotropin, decreased expression of PCBP1 protein may be a strong predictor of the malignant transformation of complete moles.
Assuntos
Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Mola Hidatiforme/metabolismo , Mola Hidatiforme/patologia , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia , Adulto , Western Blotting , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Proteínas de Ligação a DNA , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Gravidez , Prognóstico , Proteínas de Ligação a RNA , Adulto JovemRESUMO
Preeclampsia is a multisystem pregnancy disorder that is characterized by different degrees of placental malperfusion, with release of antiangiogenic factors into the circulation, leading to maternal vascular endothelial injury and high blood pressure. As a major cause of maternal and perinatal mortality and morbidity worldwide, once preeclampsia has been diagnosed, there are no curative treatments except for delivery. Lipids serve as ubiquitous and multifunctional metabolites that are integral and essential to many diverse functions on both a cellular and organismal level. Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of preeclampsia. This review comprehensively examines decades of discovery to illuminate the roles of lipids and dysregulation in the levels of various lipid classes in preeclampsia. In addition, the roles of lipids are summarized to further understand the pathogenic mechanisms of preeclampsia. Overall, the review highlights the promising potential of pathophysiology and lipid-targeting therapeutic strategies in preeclampsia.
RESUMO
Background: The results of randomized controlled studies on aspirin for the prevention of preeclampsia (PE) are conflicting, and some of the related meta-analyses also have limitations or flaws. Data sources: A search was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, with no time or language restrictions. Study eligibility criteria: Randomized controlled studies comparing aspirin for the prevention of PE were conducted. Methods: Systematic reviews were performed according to the Cochrane Manual guidelines. A fixed-effects model or a random-effects model was chosen to calculate pooled relative risks with 95% confidence intervals based on the heterogeneity of the included studies. The study aimed to investigate the effect of aspirin on the development of PE in high-risk and general populations of women. Publication bias was assessed by funnel plots. All included studies were assessed for bias by the Cochrane Manual of Bias Assessment. Subgroup analyses were conducted on the aspirin dose, time of initial aspirin intervention, and the region in which the research was conducted, to explore the effective dose of aspirin and time of initial aspirin intervention and to try to find sources of heterogeneity and publication bias. Results: A total of 39 articles were included, including 29 studies involving pregnant women at high risk for PE (20,133 patients) and 10 studies involving a general population of pregnant women (18,911 patients). Aspirin reduced the incidence of PE by 28% (RR 0.72, 95% CI 0.62-0.83) in women at high risk for PE. Aspirin reduced the incidence of PE by 30% in the general population (RR 0.70, 95% CI 0.52-0.95), but sensitivity analyses found that aspirin in the general population was not robust. A subgroup analysis showed that an aspirin dose of 75 mg/day (RR 0.50, 95% CI 0.32-0.78) had a better protective effect than other doses. Starting aspirin at 12-16 weeks (RR 0.62, 95% CI 0.53-0.74) of gestation or 17-28 weeks (RR 0.62, 95% CI 0.44-0.89) reduced the incidence of PE by 38% in women at high risk for PE, but the results were more reliable for use at 12-16 weeks. Heterogeneity and publication bias of the included studies may be mainly due to the studies completed in Asia. Conclusion: Aspirin is recommended to be started at 12-16 weeks of pregnancy in women at high risk for PE. The optimal dose of aspirin to use is 75 mg/d. Systematic review registration: [www.ClinicalTrials.gov], identifier [CRD42022319984].