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1.
BMC Psychiatry ; 24(1): 477, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937836

RESUMEN

BACKGROUND: Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain. METHODS: Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures. RESULTS: We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08). CONCLUSIONS: This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.


Asunto(s)
Trastorno del Espectro Autista , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/inmunología , Predisposición Genética a la Enfermedad/genética , Inmunofenotipificación , Inflamación/genética , Inflamación/inmunología
2.
Mol Cell Probes ; 67: 101896, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36731680

RESUMEN

Prostaglandins participate in maternal recognition of pregnancy, implantation and maintenance of gestation. Prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, might be involved in the pathogenesis of preeclampsia. In preeclampsia (PE) patients' placental tissue, we identified PGT by RNA sequencing, measured its expression pattern by quantitative real-time PCR and Western blot. PGT was found to be upregulated in preeclamptic placental tissue. The expression pattern of PGT in PE was double confirmed by eight Gene Expression Omnibus (GEO) databases. In abortion tissues at 6-8 weeks, we then observed the cellular location of PGT by Immunofluorescence technique (IF) and found PGT located in trophoblast cell of the placenta of early pregnancy. In vitro studies revealed that forced expression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation by activating Erk signaling. In vivo study, we used reduced uterine perfusion pressure (RUPP) rat model and L-NAME-induced preeclampsia-like rats to study the possible role of PGT in preeclampsia. And PGT was found to be upregulated in both preeclampsia rat models by Immunohistochemical (IHC) staining. Newly identified PGT plays an important role in trophoblast proliferation via Erk signaling, providing new insights for understanding the pathogenesis of PE.


Asunto(s)
Placenta , Preeclampsia , Humanos , Embarazo , Femenino , Ratas , Animales , Placenta/metabolismo , Placenta/patología , Preeclampsia/genética , Transducción de Señal , Proliferación Celular , Apoptosis , Prostaglandinas/metabolismo
3.
Int J Mol Sci ; 24(6)2023 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-36982197

RESUMEN

Preeclampsia (PE) is a pregnancy complication beginning after 20 weeks of pregnancy that involves high blood pressure (systolic > 140 mmHg or diastolic > 90 mmHg), with or without proteinuria. Insufficient trophoblast invasion and abnormal decidualization are involved in PE development. However, whether unhealthy placenta and decidua have the same biological activities is unclear. The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) degrades prostaglandin, and prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, helps transport prostaglandin into cells. Whether 15-PGDH and PGT are involved in PE has not been researched. In this study, we investigated the shared pathogenesis of foetal placenta and maternal decidua from the perspective of epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) and explored the combined effects of 15-PGDH and PGT on the EMT/MET of trophoblasts and decidual stromal cells (DSCs). Here, we demonstrated that placental development and decidualization both involved EMT/MET. In PE, both trophoblasts and DSCs show more epithelial patterns. Moreover, 15-PGDH expression was downregulated in the placentas but upregulated in the deciduas of PE patients. Inhibiting 15-PGDH promotes a shift to a mesenchymal pattern of trophoblasts and DSCs depending on the PGT-mediated transport of prostaglandin E2 (PGE2). In conclusion, our results showed that inhibiting 15-PGDH promotes a shift to the mesenchymal pattern of trophoblasts and DSCs and may provide a new and alternative therapy for the treatment of PE.


Asunto(s)
Placenta , Preeclampsia , Embarazo , Humanos , Femenino , Placenta/metabolismo , Trofoblastos/metabolismo , Preeclampsia/metabolismo , Dinoprostona/metabolismo , Células del Estroma/metabolismo , Decidua/metabolismo
4.
BMC Pregnancy Childbirth ; 22(1): 514, 2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35751047

RESUMEN

BACKGROUND: Due to the advancement of modern societies, the proportion of women who delay childbearing until or beyond 30 years has dramatically increased in the last three decades and has been linked with adverse maternal-neonatal outcomes. OBJECTIVE: To determine the trend in delayed childbearing and its negative impact on pregnancy outcomes. MATERIAL AND METHODS: A tertiary hospital-based retrospective study was conducted in Wuhan University Renmin Hospital, Hubei Province, China, during the years 2011-2019. The joinpoint regression analysis was used to find a trend in the delayed childbearing and the multiple binary logistic regression model was used to estimate the association between maternal age and pregnancy outcomes. RESULTS: Between 2011 and 2019, the trend in advanced maternal age (AMA ≥35 years) increased by 75% [AAPC 7.5% (95% CI: - 10.3, 28.9)]. Based on maternal education and occupation, trend in AMA increased by 130% [AAPC 11.8% (95% CI: 1.1, 23.7)] in women of higher education level, and 112.5% [AAPC 10.1% (95% CI: 9.4, 10.9)] in women of professional services. After adjusting for confounding factors, AMA was significantly associated with increased risk of gestational hypertension (aOR 1.5; 95% CI: 1.2, 2.1), preeclampsia (aOR 1.6; 95% CI: 1.4, 1.9), sever preeclampsia (aOR 1.7; 95% CI: 1.1, 2.6), placenta previa (aOR 1.8; 95% CI: 1.5, 2.2), gestational diabetes mellitus (aOR 2.5; 95% CI: 2.3, 2.9), preterm births (aOR 1.6; 95% CI: 1.4, 1.7), perinatal mortality (aOR 1.8; 95% CI: 1.3, 2.3), and low birth weight (aOR 1.3; 95% CI: 1.2, 1.4) compared with women aged < 30 years. CONCLUSION: Our findings show a marked increase in delayed childbearing and its negative association with pregnancy outcomes.


Asunto(s)
Preeclampsia , Complicaciones del Embarazo , Nacimiento Prematuro , Conducta Reproductiva , Femenino , Humanos , Recién Nacido , Edad Materna , Preeclampsia/epidemiología , Embarazo , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos
5.
J Cell Physiol ; 236(3): 2169-2177, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32776544

RESUMEN

This study aimed to investigate the mechanism by which MALAT1 regulates CRY2 expression and participates in trophoblast migration and invasion. Three patients with unexplained recurrent spontaneous abortion, four patients with missed abortion, and four women who underwent artificial miscarriages were enrolled in this study. Quantitative reverse-transcription polymerase chain reaction and western blot analysis were used to detect RNA and protein expression, respectively. Trophoblast migration and invasion were detected by wound-healing and transwell invasion assays. RNA pull-down and Co-IP assays were used to indicate the interaction between MALAT1 and FBXW7 or the interaction between FBXW7 and CRY2. The results showed significantly decreased MALAT1 expression in the villous specimens from the RSA patients relative to that in the villous specimens from the missed abortion patients and the normal villous specimens. MALAT1 promoted trophoblast cell migration and invasion by negatively regulating CRY2 protein expression. MALAT1 recruited FBXW7 to impair CRY2 protein stability. In conclusion, MALAT1 downregulation in trophoblasts might be related to miscarriage. MALAT1 may recruit the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin-mediated degradation and participate in trophoblast migration and invasion.


Asunto(s)
Criptocromos/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteolisis , ARN Largo no Codificante/metabolismo , Trofoblastos/citología , Trofoblastos/metabolismo , Ubiquitina/metabolismo , Aborto Habitual/genética , Línea Celular , Movimiento Celular/genética , Criptocromos/genética , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Regulación de la Expresión Génica , Humanos , Estabilidad Proteica , ARN Largo no Codificante/genética
6.
Clin Infect Dis ; 72(5): 862-864, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-32182347

RESUMEN

We present 2 cases of coronavirus disease 2019 (COVID-19)-associated severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the third trimester of pregnancy. Both mothers and newborns had excellent outcomes. We failed to identify SARS-CoV-2 in all of the products of conception and the newborns. This report provided evidence of low risk of intrauterine infection by vertical transmission of SARS-CoV-2.


Asunto(s)
COVID-19 , Coronavirus , Complicaciones Infecciosas del Embarazo , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Resultado del Embarazo , SARS-CoV-2
7.
J Obstet Gynaecol Res ; 47(4): 1344-1352, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33462908

RESUMEN

AIM: To evaluate perinatal outcomes regarding clinical presentation in pregnancy and the vertical transmission potential of COVID-19. METHODS: Clinical records, laboratory findings, and chest computed tomography (CT) scans were retrospectively reviewed from 20 pregnant patients with laboratory-confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University and The Third Hospital of Wuhan, from Jan 20 to Mar 16, 2020, including three in the first-trimester, two in the second-trimester, and 15 in the third-trimester. Evidence of vertical transmission was assessed by testing for neonatal throat swab samples. The pathological changes of COVID-19 on the placenta is evaluated by hematoxylin-eosin staining. RESULTS: The most common symptoms of the pregnant women with SARS-CoV-2 infection were fever and cough, which is comparable to the nonpregnant adults with COVID-19 infection. Nobody was transferred to intensive care unit (ICU) for treatment and there were no maternal and neonatal deaths. However, there was one case with induced abortions on first-trimester (due to pregnant woman's concerns about COVID-19), one diagnosed with ectopic pregnancy, no intrauterine fetal deaths during the study period. Delivery occurred in 15 patients in the third trimester. Their incidence of preterm birth was 20%. Three of the four preterm births were spontaneous. The average length of stay was 20.77 days. No neonatal SARS-CoV-2 infection was detected. There were two placentas found with acute chorioamnionitis, one showed normal placenta morphology. CONCLUSION: In this case series study, COVID-19 had no short-term adverse effect on pregnant women except premature birth. The vertical transmission of SARS-CoV-2 did not occur in our study.


Asunto(s)
COVID-19/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/virología , Nacimiento Prematuro/epidemiología , Adulto , COVID-19/complicaciones , COVID-19/patología , China/epidemiología , Corioamnionitis/epidemiología , Femenino , Humanos , Recién Nacido , Tiempo de Internación , Masculino , Placenta/patología , Embarazo , Complicaciones Infecciosas del Embarazo/patología , Estudios Retrospectivos , SARS-CoV-2 , Adulto Joven
8.
J Res Med Sci ; 26: 38, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34484370

RESUMEN

BACKGROUND: Preeclampsia (PE) and premature rupture of membrane (PROM) are considered significant risk factors for lower neonatal birth weight and birth length. However, very limited studies have reported the impact of PE and PROM on neonatal birth weight and birth length by gestational week. Therefore, we aimed to determine the effect of PE and PROM on neonatal birth weight and length by gestational age. MATERIALS AND METHODS: A total of 9707 singleton neonates were selected for this study. All the data were collected and documented in the obstetric register by the trained nurses in the Gynecology and Obstetrics Department. RESULTS: The neonatal mean birth weights and birth lengths were statistically significantly (P < 0.05) lowered among preeclamptic mothers compared to mothers without PE throughout the gestational age. Statistically significantly (P < 0.05) lowered mean birth weights and birth lengths were found among neonates born to mothers with PROM than among neonates born to mothers without PROM by all gestational weeks except for 32 weeks and 36 weeks. Moreover, in a multiple linear regression model, PE and PROM were significantly negatively associated with neonatal birth weights and birth lengths by almost all gestational weeks (ß <0, P < 0.05). CONCLUSION: We concluded that after adjustment for covariates and confounding factors, PE and PROM had a significantly negative association with neonatal birth weights and birth lengths by all gestational weeks.

9.
Am J Obstet Gynecol ; 223(1): 111.e1-111.e14, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32335053

RESUMEN

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.


Asunto(s)
Infecciones por Coronavirus/patología , Neumonía Viral/patología , Complicaciones Infecciosas del Embarazo/virología , Aborto Espontáneo/virología , Adulto , Líquido Amniótico/virología , Betacoronavirus , COVID-19 , China , Infecciones por Coronavirus/complicaciones , Femenino , Sangre Fetal/virología , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Pandemias , Neumonía Viral/complicaciones , Embarazo , Complicaciones Infecciosas del Embarazo/patología , Resultado del Embarazo , Nacimiento Prematuro/virología , SARS-CoV-2
10.
Angew Chem Int Ed Engl ; 55(14): 4537-41, 2016 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-26929123

RESUMEN

Stretchable electrochemical sensors are conceivably a powerful technique that provides important chemical information to unravel elastic and curvilinear living body. However, no breakthrough was made in stretchable electrochemical device for biological detection. Herein, we synthesized Au nanotubes (NTs) with large aspect ratio to construct an effective stretchable electrochemical sensor. Interlacing network of Au NTs endows the sensor with desirable stability against mechanical deformation, and Au nanostructure provides excellent electrochemical performance and biocompatibility. This allows for the first time, real-time electrochemical monitoring of mechanically sensitive cells on the sensor both in their stretching-free and stretching states as well as sensing of the inner lining of blood vessels. The results demonstrate the great potential of this sensor in electrochemical detection of living body, opening a new window for stretchable electrochemical sensor in biological exploration.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas/instrumentación , Dimetilpolisiloxanos/química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Microscopía Electrónica de Rastreo
11.
Int J Geriatr Psychiatry ; 30(2): 156-65, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25475551

RESUMEN

OBJECTIVE: The objective of the study was to investigate the association between peripheral levels of C-reactive protein (CRP) and cognitive decline that is defined by 2-5 years of cognitive change in general cognitive function or specific cognitive domain. METHODS: We searched PubMed and Google for prospective/longitudinal studies that report the association between peripheral levels of CRP and risk of cognitive decline in the nondementia population. RESULTS: Out of 479 related articles from PubMed and Google, four studies with a total of 5255 non-demented subjects that report odds ratio (OR)/relative risk/hazard ratio of CRP levels and decline in general cognition met our criteria for meta-analysis. The association between higher levels of CRP and risk of global cognitive decline was weak but significant (OR, 1.27 [95% CI, 1.02 to 1.58]). However, the systematic review from six other articles that were not suitable for meta-analysis revealed a marginal association between CRP and cognitive decline in certain domains. CONCLUSION: Our analysis demonstrated a weak association between peripheral CRP level and global cognitive decline. Because of the small number of included studies and varied methodologies that they applied, caution should be taken when generalizing our finding to the full range of cognitive changes in different cognitive domains observed in non-demented people.


Asunto(s)
Proteína C-Reactiva/metabolismo , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Humanos , Oportunidad Relativa , Escalas de Valoración Psiquiátrica , Factores de Riesgo
12.
J Affect Disord ; 362: 615-622, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39029663

RESUMEN

BACKGROUNDS: Empirical investigations have shown an association between gut microbiota and postpartum depression (PPD); nevertheless, the precise cause-and-effect relationship between these two variables remains ambiguous. This research aimed to examine the possible reciprocal causal relationship between the gut microbiota and PPD. METHODS: In this work, we used Mendelian randomization (MR) to analyze the relationship between the gut microbiota (n = 18,340) and PPD (n = 67,205). We obtained the relevant SNPs from publicly accessible genome-wide association studies (GWAS). The SNP estimations were combined by the inverse-variance weighted (IVW) method, including sensitivity analyses such as weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO). RESULTS: We have identified strong correlations between six bacterial characteristics and the likelihood of developing PPD. Our research revealed that the genus Ruminococcaceae UCG010, the family Veillonellaceae, and the class Clostridia had a beneficial effect on preventing PPD. The class Alphaproteobacteria, genus Slackia, and order NB1n were found to have a significant negative impact on PPD. The sensitivity studies conducted on these bacterial features consistently confirmed these finding. LIMITATIONS: It is crucial to acknowledge that our study was conducted just within a European society, which may restrict its applicability to other groups. CONCLUSIONS: The findings from our MR investigation indicate a potential causal relationship between certain kinds of gut bacteria and PPD. Additional investigation is required to elucidate the influence of gut microbiota on the advancement of PPD.


Asunto(s)
Depresión Posparto , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Microbioma Gastrointestinal/genética , Femenino , Depresión Posparto/genética , Depresión Posparto/microbiología
13.
J Clin Hypertens (Greenwich) ; 26(5): 474-482, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38476059

RESUMEN

Patients with systemic autoimmune diseases, such as systemic lupus erythematosus, were at a higher risk for preeclampsia. The causal relationship between immunological inflammation and preeclampsia (PE) remains uncertain. We aimed to investigate the causal relationship between circulating immune inflammation and PE. Genetically predicted blood immune cells and circulating inflammatory proteins were identified using two genome-wide association studies (GWAS). We used a two-sample Mendelian randomization (MR) method to determine whether circulating immunological inflammation causes PE. Our findings indicated that ten immunophenotypes were identified to be significantly associated with PE risk: CD62L- Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L- myeloid Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell Absolute Count, CD62L- myeloid Dendritic Cell %Dendritic Cell, CD62L- CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L- CD86+ myeloid Dendritic Cell Absolute Count, CD16 on CD14+ CD16+ monocyte, HLA DR+ Natural Killer Absolute Count, and T cell Absolute Count. Ninety-one inflammation-related proteins had no statistically significant effect on PE following false discovery rate (FDR) correction. Certain proteins exhibited unadjusted low p-values that merited mention. These proteins include interleukin-10 (OR = 0.76, 95%CI = 0.63-0.93, p = .006), fibroblast growth factor 21 (OR = 1.23, 95%CI = 1.01-1.47, p = .035), and Caspase 8 (OR = 0.65, 95%CI = 0.50-0.85, p = .001). The ELISA analysis demonstrated elevated levels of FGF-21 and decreased levels of IL-10 and Caspase-8 in the plasma of patients with PE. These findings reveal that immunophenotypes and circulating inflammatory proteins may induce PE, confirming the importance of peripheral Immunity-Inflammation in PE. The discovery has the potential to lead to earlier detection and more effective treatment techniques.


Asunto(s)
Estudio de Asociación del Genoma Completo , Inflamación , Análisis de la Aleatorización Mendeliana , Preeclampsia , Humanos , Femenino , Preeclampsia/inmunología , Preeclampsia/sangre , Preeclampsia/genética , Análisis de la Aleatorización Mendeliana/métodos , Embarazo , Inflamación/inmunología , Inflamación/sangre , Inflamación/genética , Interleucina-10/sangre , Interleucina-10/genética , Células Dendríticas/inmunología , Adulto , Inmunofenotipificación/métodos
14.
J Hazard Mater ; 479: 135594, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39191013

RESUMEN

Benz[a]anthracene (BaA), a hazardous polycyclic aromatic hydrocarbon classified by the EPA, is a probable reproductive toxicant. Epidemiological studies suggest that BaA exposure may be a risk factor for recurrent miscarriage (RM). However, the underlying mechanisms are not well understood. This study identified DEC1 as a key gene through RNA-seq and single-cell RNA sequencing analysis. DEC1 expression was found to be downregulated in villous tissues from women with RM and in primary extravillous trophoblasts (EVTs) exposed to BaA. BaA suppressed DEC1 expression by promoting abnormal methylation patterns. Further analysis revealed that ARHGAP5 is a direct target of DEC1 in EVTs, where DEC1 inhibits trophoblast invasion by directly regulating ARHGAP5 transcription. Additionally, BaA destabilized matrix metalloproteinase 2 (MMP2) by activating the aryl hydrocarbon receptor (AhR) and promoting E3 ubiquitin ligase MID1-mediated degradation. In a mouse model, BaA induced miscarriage by modulating the DEC1/ARHGAP5 and MID1/MMP2 axes. Notably, BaA-induced miscarriage in mice was prevented by DEC1 overexpression or MID1 knockdown. These findings indicate that BaA exposure leads to miscarriage by suppressing the DEC1/ARHGAP5 pathway and enhancing the MID1/MMP2 pathway in human EVTs.

15.
Placenta ; 145: 27-37, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38039841

RESUMEN

Gestational diabetes mellitus (GDM) is a common pregnancy complication with a high incidence in women; however, its pathophysiology remains unknown. Our previous study suggested that the circCHD2/miR-33b-3p/ULK1 axis may be involved in GDM pathogenesis. However, the mechanism through which circCHD2 regulates GDM development requires further investigation. We found that high-glucose (HG, 25 mmol/L) significantly induced the expression of circCHD2, increased autophagy and apoptosis, and decreased cell viability in human placental trophoblast HTR-8/SVneo cells. In contrast, the downregulation of circCHD2 significantly attenuated the effects of HG on HTR-8/SVneo cells. MiR-33b-3p downregulated in the placenta of GDM patients was reduced by HG and detected as a target of circCHD2 using bioinformatics analysis, a dual-luciferase reporter assay, and qRT-PCR assay. Further studies showed that the inhibition of miR-33b-3p significantly blocked the effects of circCHD2 downregulation on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. ULK1 is a target of miR-33b-3p, based on bioinformatics analysis, a dual-luciferase reporter assay, qRT-PCR assay, and Western blot analysis. Compared to miR-33b-3p, ULK1 is upregulated in the placenta of GDM patients. ULK1 overexpression notably blocked the effects of miR-33b-3p mimics on cell viability, apoptosis, and autophagy in HG-treated HTR-8/SVneo cells. These findings suggested that circCHD2 acts as an autophagy promoter via the miR-33b-3p/ULK1 axis to induce apoptosis in HTR-8/SVneo cells, suggesting that circCHD2 is a potential diagnostic and therapeutic target for GDM.


Asunto(s)
Diabetes Gestacional , MicroARNs , ARN Circular , Femenino , Humanos , Embarazo , Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Proliferación Celular/fisiología , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Luciferasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , ARN Circular/genética , ARN Circular/metabolismo
16.
Biomedicines ; 11(8)2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37626824

RESUMEN

Pre-eclampsia (PE) is a gestational hypertensive disorder that is characterized by hypertension and proteinuria, typically occurring after 20 weeks of gestation. Despite its global impact on pregnant women, the precise pathogenic mechanisms of PE remain unclear. Dysregulated lipid metabolism and immune cell infiltration contribute to PE development. Our study aimed to identify lipid-metabolism-related genes (LMRG-PEs) and investigate their association with immune infiltration. We utilized the "Seurat" R package for data quality control, cell clustering, and marker gene identification. The "SingleR" package enabled the matching of marker genes to specific cell types. Pseudotemporal ordering analysis was conducted using the "Monocle" package. Weighted correlation network analysis (WGCNA), gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) approaches were employed to explore lipid-metabolism-related genes, while potential targeted drugs were predicted using the drug-gene interaction database (DGIdb). Hub gene expression was validated through RT-qPCR. By analyzing single-cell RNA sequencing data, we identified and classified 20 cell clusters into 5 distinct types. Differential gene expression analysis revealed 186 DEGs. WGCNA identified 9 critical modules and 265 genes significantly associated with PE diagnosis, emphasizing the importance of the core genes PLA2G7 and PTGS2. RT-qPCR confirmed the significantly decreased expression of PLA2G7 and PTGS2 in PE patient tissues. These findings offer valuable insights into the molecular mechanisms of PE, particularly those involving lipid metabolism and immune infiltration. The identified hub genes have potential as therapeutic targets and biomarkers for future research and clinical applications.

17.
Int J Gynaecol Obstet ; 161(3): 1069-1074, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36572390

RESUMEN

OBJECTIVE: To explore the interactions between cervical length (CL) and placenta accreta spectrum (PAS) on severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: A retrospective case-control study was conducted at four medical centers in China, and 588 patients with placenta previa were included. The logistic regression analysis and restricted cubic splines (RCS) were used to evaluate the association between CL and SPPH. Furthermore, the joint effect of CL and PAS on SPPH was assessed, and the additive and multiplicative interactions were calculated. RESULTS: After adjusting for potential confounders, the negative linear dose-response relationship was confirmed by RCS, and the change of odds ratio (OR) was more significant when CL was 2.5 cm or less. The risk of SPPH was significantly higher when CL of 2.5 cm or less co-existed with placenta increta/percreta than when CL of 2.5 cm less, or placenta increta/percreta existed alone (adjusted OR [aOR]CL ≤2.5cm&placenta accreta/non-PAS 3.40, 95% confidence interval [CI] 1.37-8.45; aORplacenta increta/percreta&CL >2.5cm 4.75, 95% CI 3.03-7.47; aORCL ≤2.5cm&placenta increta/percreta 14.51, 95% CI 6.08-34.64), and there might be additive interaction between CL and placenta increta/percreta on SPPH (attributable proportion due to interaction 50.7%, 95% CI 6.1%-95.3%). CONCLUSION: If CL was routinely performed during PAS evaluation, the increased OR of short CL and PAS could allow better patient preparation through counseling.


Asunto(s)
Placenta Accreta , Placenta Previa , Hemorragia Posparto , Embarazo , Humanos , Femenino , Placenta Accreta/diagnóstico por imagen , Placenta Previa/diagnóstico por imagen , Estudios Retrospectivos , Estudios de Casos y Controles , Hemorragia Posparto/diagnóstico por imagen , Hemorragia Posparto/etiología , Placenta
18.
Malawi Med J ; 34(2): 123-131, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35991813

RESUMEN

Background: Neonatal birth weight and length are important indicators of neonatal survival and morbidity during later life and are influenced by maternal factors and obstetrical complications. Therefore, we aimed to determine the relationship of maternal factors and obstetric complications with term singleton vs term twin neonatal outcomes in Wuhan University Renmin Hospital, Hubei, China. Methods: A total of 10517 neonatal births were recorded in a tertiary-hospital-based retrospective study and term singleton (n=7787) and term twins (n=169) were included for data analysis. Birth weight and birth length were measured immediately after birth. Correlation, independent student t-test, and backward multiple linear regression were used for statistical analysis. Results: Women with singleton gestation have an increased rate of obstetric complications compared to women with twin gestation. However, a higher frequency of cesarean section and breech were found in twin gestation compared to singleton gestation. Weight before pregnancy, gestational weight gain, and gestational diabetes mellitus were significantly positive (p<0.05) associated with singleton neonatal birth length and weight. In contrast, preeclampsia, placenta previa, oligohydramnios, premature rupture of membrane, breech, and multiparity had a significantly negative (p<0.05) association with singleton neonatal birth length and weight. Maternal age was significantly positive (p<0.05) associated with only singleton neonatal birth weight. Moreover, the nuchal cord was significantly positive (p<0.05) associated with singleton neonatal birth length. On the other hand, maternal age and multiparity were significantly positive (p<0.05) associated with twins' neonatal birth length and weight. Furthermore, gestational weight gain was significantly positive (p<0.05) associated with only twins' neonatal birth weight. Conclusion: In term gestation, obstetric complications were significantly associated with singleton birth size rather than twin birth size.


Asunto(s)
Ganancia de Peso Gestacional , Resultado del Embarazo , Peso al Nacer , Cesárea , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Estudios Retrospectivos
19.
Front Oncol ; 12: 977618, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36059660

RESUMEN

Cancer is one of the most harmful diseases, while pregnancy is a common condition of females. Placenta is the most important organ for fetal growth, which has not been fully understand. It's well known that placenta and solid tumor have some similar biological behaviors. What's more, decidua, the microenvironment of placenta, and metabolism all undergo adaptive shift for healthy pregnancy. Interestingly, decidua and the tumor microenvironment (TME); metabolism changes during pregnancy and cancer cachexia all have underlying links. However, whether the close link between pregnancy and cancer can bring some new ideas to treat cancer is still unclear. So, in this review we note that pregnancy may offer clues to treat cancer related to three categories: from cell perspective, through the shared development process of the placenta and cancer; from microenvironment perspective, though the shared features of the decidua and TME; and from metabolism perspective, through shared metabolites changes during pregnancy and cancer cachexia. Firstly, comparing gene mutations of both placenta and cancer, which is the underlying mechanism of many similar biological behaviors, helps us understand the origin of cancer and find the key factors to restore tumorigenesis. Secondly, exploring how decidua affect placenta development and similarities of decidua and TME is helpful to reshape TME, then to inhibit cancer. Thirdly, we also illustrate the possibility that the altered metabolites during pregnancy may reverse cancer cachexia. So, some key molecules changed in circulation of pregnancy may help relieve cachexia and make survival with cancer realized.

20.
Sci Rep ; 12(1): 5048, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35322808

RESUMEN

The universal two-child policy (TCP; 2016) in China has affected many aspects of maternal-neonatal health. A tertiary hospital-based retrospective study (2011-2019) was used to find the association of these policy changes with maternal age and pregnancy outcomes in women with AMA (≥ 35 years) in the Hubei Province, China. The proportion of neonatal births to women with AMA increased by 68.8% from 12.5% in the one-child policy (OCP) period to 21.1% in the universal TCP period [aOR 1.76 (95% CI: 1.60, 1.93)]. In the univariate analysis, the proportion of preterm births (29.4% to 24.1%), low birth weight (LBW) (20.9% to 15.9%), and hypertensive disorders of pregnancy (HDP) (11.5% to 9.2%) significantly (p < 0.05) decreased in women with AMA from the OCP period to universal TCP period. However, the proportion of intrauterine growth restriction (IUGR) (0.2% to 0.7%) and gestational diabetes mellitus (GDM) (1.7% to 15.6%) was significantly (p < 0.05) increased over the policy changes. After adjusting for confounding factors, only the risk of GDM increased [aOR 10.91 (95% CI: 6.05, 19.67)] in women with AMA from the OCP period to the universal TCP period. In conclusion, the risk of GDM increased in women with AMA from the OCP period to the universal TCP period.


Asunto(s)
Diabetes Gestacional , Política de Planificación Familiar , Nacimiento Prematuro , China/epidemiología , Diabetes Gestacional/epidemiología , Femenino , Humanos , Recién Nacido , Edad Materna , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos
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