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1.
J Pak Med Assoc ; 71(4): 1081-1088, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34125747

RESUMO

OBJECTIVE: This study aimed to isolate human umbilical cord blood derived endothelial colony forming cells (ECFCs) followed by their integration free reprogramming towards induced pluripotent stem cells (iPSCs) and molecular characterization of both cell types using multicolour flowcytometery and immunofluorescence respectively. METHODS: The cord blood was collected from 37-39 weeks of gestational ages after C-section ex-utero from Dow University Hospital. The ECFCs isolated after ficoll based separation of cord blood mononuclear cells (CBMNCs) which on emergence characterized through flow cytometry and reprogrammed towards induced pluripotent stem cells (iPSCs) using episomal vectors, the iPSCs were characterized using immunofluorescence. The study was conducted at Stem Cells and Regenerative lab, Dow Research Institute of Biotechnology and Biomedical Sciences, Dow University of health sciences OJHA campus. The study time duration was about one year (October 2017-October 2018); study design was in vitro experimental. The sample size of the study was n=3. RESULTS: The isolated ECFCs were evaluated using flowcytometery which showed positive expression for CD31, CD34, CD146 cell surface markers and negative for CD90. The successful reprogramming of ECFCs towards iPSCs was confirmed by immunofluorescence using OCT-4 which is considered to be a master regulator of pluripotency. CONCLUSIONS: To the best of our knowledge this study was the first attempt to integration free reprogramming of cord blood derived endothelial colony forming cells towards induced pluripotent stem using episomal plasmids. Cells that have been isolated from cord blood and those that have been reprogrammed both have potential therapeutic applications in regenerative medicine.


Assuntos
Células-Tronco Pluripotentes Induzidas , Reprogramação Celular , Sangue Fetal , Humanos , Leucócitos Mononucleares , Plasmídeos/genética
2.
Int J Mol Sci ; 22(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064452

RESUMO

Polycystic Kidney Disease (PKD) is a disorder that affects the kidneys and other organs, and its major forms are encoded by polycystin-1 (PC1) and polycystin-2 (PC2), as PKD1 and PKD2. It is located sandwiched inside and outside cell membranes and interacts with other cells. This protein is most active in kidney cells before birth, and PC1 and PC2 work together to help regulate cell proliferation, cell migration, and interactions with other cells. The molecular relationship and the function between PKD1 and cancer is well known, such as increased or decreased cell proliferation and promoting or suppressing cell migration depending on the cancer cell type specifically. However, its function in stem cells has not been revealed. Therefore, in this study, we investigated the biological function of PC1 and umbilical cord blood-derived mesenchymal stem cell (UCB-MSC). Furthermore, we assessed how it affects cell migration, proliferation, and the viability of cells when expressed in the PKD1 gene. In addition, we confirmed in an ex vivo artificial tooth model generated by the three-dimension printing technique that the ability to differentiate into osteocytes improved according to the expression level of the stemness markers when PKD1 was expressed. This study is the first report to examine the biological function of PKD1 in UCB-MSC. This gene may be capable of enhancing differentiation ability and maintaining long-term stemness for the therapeutic use of stem cells.


Assuntos
Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismo , Osteócitos/metabolismo , Canais de Cátion TRPP/genética , Células A549 , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Linhagem Celular , Movimento Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos/métodos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Expressão Gênica , Células HEK293 , Humanos , Células MCF-7 , Células-Tronco Mesenquimais/citologia , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Osteócitos/citologia , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Canais de Cátion TRPP/metabolismo , Transfecção , Transgenes
3.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070163

RESUMO

Preeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children's health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, although causative factors for the latter have remained elusive. MicroRNA (miRNA) modifications are a potential mechanism through which exposure to an altered environment translates into the development of chronic disease. In this study, we examined whether development of preeclampsia corresponds to alterations of miRNAs in maternal- and cord-blood-derived EPC. To test this end, we analyzed maternal and neonatal miRNAs via RNA sequencing from endothelial cells of preeclamptic and healthy controls in different cell culture passages. We were able to demonstrate differentially represented miRNAs in all groups. Hsa-miR-1270 showed significantly different levels in cord blood EPC from preeclampsia versus control and was negatively correlated with mRNA levels of its predicted targets ANGPTL7 and TFRC. Transfection with an hsa-miR-1270 inhibitor decreased the tube formation capacity and chemotactic motility but did not change proliferation in vitro. Target predictions and gene set enrichment analyses identified alternative splicing as a significantly enriched pathway for hsa-miR-1270. The top miRNAs in three other groups were predicted to target transcriptional and developmental pathways. Here, we showed for the first time significantly different levels of miRNAs and differently represented mRNA levels of predicted target genes in EPC derived from preeclampsia. Understanding the effects of preeclampsia on the epigenetic mechanisms of EPC will be crucial and may provide initial insights for further evaluation of the benefits of therapies targeting this cell population.


Assuntos
Células Progenitoras Endoteliais/metabolismo , MicroRNAs/genética , Pré-Eclâmpsia/genética , Adulto , Proteínas Semelhantes a Angiopoietina/genética , Antígenos CD/genética , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Quimiotaxia , Feminino , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Perfilação da Expressão Gênica , Humanos , Recém-Nascido , Masculino , MicroRNAs/sangue , MicroRNAs/metabolismo , Neovascularização Patológica/genética , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Gravidez , RNA Mensageiro/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Transferrina/genética , Adulto Jovem
4.
Int J Mol Sci ; 22(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067339

RESUMO

Dephosphorylation inhibitor calyculin A (cal A) has been reported to inhibit the disappearance of radiation-induced γH2AX DNA repair foci in human lymphocytes. However, other studies reported no change in the kinetics of γH2AX focus induction and loss in irradiated cells. While apoptosis might interplay with the kinetics of focus formation, it was not followed in irradiated cells along with DNA repair foci. Thus, to validate plausible explanations for significant variability in outputs of these studies, we evaluated the effect of cal A (1 and 10 nM) on γH2AX/53BP1 DNA repair foci and apoptosis in irradiated (1, 5, 10, and 100 cGy) human umbilical cord blood lymphocytes (UCBL) using automated fluorescence microscopy and annexin V-FITC/propidium iodide assay/γH2AX pan-staining, respectively. No effect of cal A on γH2AX and colocalized γH2AX/53BP1 foci induced by low doses (≤10 cGy) of γ-rays was observed. Moreover, 10 nM cal A treatment decreased the number of all types of DNA repair foci induced by 100 cGy irradiation. 10 nM cal A treatment induced apoptosis already at 2 h of treatment, independently from the delivered dose. Apoptosis was also detected in UCBL treated with lower cal A concentration, 1 nM, at longer cell incubation, 20 and 44 h. Our data suggest that apoptosis triggered by cal A in UCBL may underlie the failure of cal A to maintain radiation-induced γH2AX foci. All DSB molecular markers used in this study responded linearly to low-dose irradiation. Therefore, their combination may represent a strong biodosimetry tool for estimation of radiation response to low doses. Assessment of colocalized γH2AX/53BP1 improved the threshold of low dose detection.


Assuntos
Apoptose/efeitos dos fármacos , Sangue Fetal/efeitos dos fármacos , Histonas/metabolismo , Linfócitos/efeitos dos fármacos , Toxinas Marinhas/farmacologia , Oxazóis/farmacologia , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Sangue Fetal/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfócitos/metabolismo , Microscopia de Fluorescência/métodos , Fosforilação/efeitos dos fármacos
5.
Sci Total Environ ; 787: 147621, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34000534

RESUMO

BACKGROUND: Pregnant women and their fetuses are exposed to multiple toxic metals that together with variations in essential element levels may alter epigenetic regulation, such as DNA methylation. OBJECTIVES: The aim of the study was to investigate the associations between gestational levels of toxic metals and essential elements and mixtures thereof, with global DNA methylation levels in pregnant women and their newborn children. METHODS: Using 631 mother-child pairs from a prospective birth cohort (The Norwegian Mother, Father and Child Cohort Study), we measured maternal blood concentration (gestation week ~18) of five toxic metals and seven essential elements. We investigated associations as individual exposures and two-way interactions, using elastic net regression, and total mixture, using quantile g-computation, with blood levels of 5-methylcytocine (5mC) and 5-hydroxymethylcytosine (5hmC) in mothers during pregnancy and their newborn children (cord blood). Multiple testing was adjusted for using the Benjamini and Hochberg false discovery rate (FDR) approach. RESULTS: The most sensitive marker of DNA methylation appeared to be 5mC levels. In pregnant mothers, elastic net regression indicated associations between 5mC and selenium and lead (non-linear), while in newborns results indicated relationships between maternal selenium, cobalt (non-linear) and mercury and 5mC, as well as copper (non-linear) and 5hmC levels. Several possible two-way interactions were identified (e.g. arsenic and mercury, and selenium and maternal smoking in newborns). None of these findings met the FDR threshold for multiple testing. No net effect was observed in the joint (mixture) exposure-approach using quantile g-computation. CONCLUSION: We identified few associations between gestational levels of several toxic metals and essential elements and global DNA methylation in pregnant mothers and their newborn children. As DNA methylation dysregulation might be a key mechanism in disease development and thus of high importance for public health, our results should be considered as important candidates to investigate in future studies.


Assuntos
Metilação de DNA , Gestantes , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Humanos , Lactente , Recém-Nascido , Exposição Materna/efeitos adversos , Noruega , Gravidez , Estudos Prospectivos
6.
Eur J Obstet Gynecol Reprod Biol ; 261: 139-143, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33934025

RESUMO

AIM: To evaluate the association between lactate concentrations in fetal blood samples and the different advanced labour stages. METHODS: Eighteen-month prospective population-based clinical study of 187 singleton pregnant women in labour who were monitored by fetal blood sampling (FBS) because of non-reassuring intrapartum CTG results at Kuopio University Hospital, Finland. Peripheral lactate concentration and pH were analysed at different stages of labour and in umbilical arterial samples immediately after delivery. RESULTS: FBS samples (N = 350) were obtained from 5.4 % of all women in labour during the study period, and 48 % had spontaneous delivery, 27 % had vacuum-assisted vaginal delivery, and 25 % had nonelective Caesarean delivery. FBS lactate levels increased 4-11% with every 1-2 cm of cervical dilation and 18 % from early labour to fully dilated cervix. In 42 women with at least two FBSs, lactate levels increased significantly from the early I stage of labour and up to a fully dilated cervix. Lactate values were significantly higher in umbilical arterial samples compared to FBSs. Sensitivity of the highest FBS lactate values for the detection of birth asphyxia were considerably low varying between 42.9-57.1%. CONCLUSION: FBS lactate levels were related to the stage of labour during vaginal delivery attempt. Wide range of lactate levels during labour complicates its use as a predictor of birth asphyxia.


Assuntos
Trabalho de Parto , Cesárea , Parto Obstétrico , Feminino , Sangue Fetal , Finlândia , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos
7.
Ceska Gynekol ; 86(2): 80-85, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34020553

RESUMO

OBJECTIVE: Fetal Inflammatory Response Syndrome (FIRS) is a serious complication accompanied by increased neonatal mortality and morbidity. Early dia-gnosis of FIRS is essential to detect high risk infants. The aim of the study was to evaluate the correlation between interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) in cord blood and histologically proven funisitis;chorioamnionitis in high-risk infants after preterm birth. METHODS: Blood sampling for the measurement of inflammatory bio-markers was performed immediately after placental delivery and umbilical cutting. Umbilical and placental inflammatory changes were assessed using a recently released scoring system (Amsterdam Placental Workshop Group Consensus). RESULTS: One hundred preterm infants (30.5 ± 2.5 gestational week, birth weight 1,443 ± 566 grams) and 21 health term infants were analyzed. Histologic chorioamnionitis was confirmed in 19% cases and chorioamnionitis with funisitis in 7% cases. Thirty-three infants (33%) fulfilled criteria of FIRS (funistis and/ or umbilical IL-6 > 11 ng/ L). The presence of FIRS correlated significantly with maternal leukocytosis (P < 0.001), preterm premature rupture of membrane (P < 0.001) and preterm uterine contraction (P < 0.0001). In comparison to preterm and healthy term infants we found statistically significant higher levels of umbilical inflammatory bio­markers (IL-6, PCT, CRP) in FIRS group (P < 0.0001). Composite mortality and morbidity (bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia) was higher in FIRS group (28.1 vs 22.4% in preterm group). However, the difference was not statistically significant (P = 0.53). CONCLUSION: Our study confirmed the correlation of umbilical inflammatory bio­markers levels (IL-6, PCT, CRP) and the presence of FIRS. We did not find significant adverse impact of FIRS on neonatal mortality and morbidity. Nevertheless, our results could be influenced by the size of study group and strict inclusion criteria (only cases after C-section were analyzed).


Assuntos
Corioamnionite , Nascimento Prematuro , Proteína C-Reativa , Corioamnionite/diagnóstico , Feminino , Sangue Fetal , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Interleucina-6 , Gravidez , Pró-Calcitonina
8.
Environ Health Prev Med ; 26(1): 59, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022817

RESUMO

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.


Assuntos
Saúde da Criança , Poluentes Ambientais/efeitos adversos , Hipersensibilidade/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Saúde Ambiental , Feminino , Sangue Fetal/química , Seguimentos , Crescimento/efeitos dos fármacos , Humanos , Hipersensibilidade/etiologia , Lactente , Japão/epidemiologia , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Prevalência
9.
Nutrients ; 13(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806689

RESUMO

Maternal supplementation of docosahexaenoic acid (DHA) during pregnancy has been recommended due to its role in infant development, but its effect on materno-fetal DHA status is not well established. We evaluated the associations between DHA supplementation in pregnant women with obesity or gestational diabetes mellitus (GDM) and maternal and neonatal DHA status. Serum fatty acids (FA) were analyzed in 641 pregnant women (24 weeks of gestation) and in 345 venous and 166 arterial cord blood samples of participants of the NELA cohort. Obese women (n = 47) presented lower DHA in serum than those lean (n = 397) or overweight (n = 116) before pregnancy. Linoleic acid in arterial cord was elevated in obese women, which indicates lower fetal retention. Maternal DHA supplementation (200 mg/d) during pregnancy was associated with enhanced maternal and fetal DHA levels regardless of pre-pregnancy body mass index (BMI), although higher arterial DHA in overweight women indicated an attenuated response. Maternal DHA supplementation was not associated with cord venous DHA in neonates of mothers with GDM. The cord arteriovenous difference was similar for DHA between GDM and controls. In conclusion, maternal DHA supplementation during pregnancy enhanced fetal DHA status regardless of the pre-pregnancy BMI while GDM may reduce the effect of DHA supplementation in newborns.


Assuntos
Diabetes Gestacional/sangue , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/análise , Ácidos Graxos/sangue , Obesidade/sangue , Complicações na Gravidez/sangue , Adulto , Índice de Massa Corporal , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Estudos Prospectivos
10.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915948

RESUMO

Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting need for ex vivo HSPC expansion. To establish a more efficient method to expand UCB HSPCs, we developed the bioactive peptide named SL-13R and cultured UCB HSPCs (CD34+ cells) with SL-13R in animal component-free medium containing a cytokine cocktail. Following 9 days of culture with SL-13R, the numbers of total cells, CD34+, CD38- cells, and hematopoietic stem cell (HSC)-enriched cells were significantly increased relative to control. Transplantation of cells cultured with SL-13R into immunodeficient NOD/Shi-scid/IL-2Rγ knockout mice confirmed that they possess long-term reconstitution and self-renewal ability. AHNAK, ANXA2, and PLEC all interact with SL-13R. Knockdown of these genes in UCB CD34+ cells resulted in reduced numbers of hematopoietic colonies relative to SL-13R-treated and non-knockdown controls. In summary, we have identified a novel bioactive peptide SL-13R promoting expansion of UCB CD34+ cells with long-term reconstitution and self-renewal ability, suggesting its clinical use in the future.


Assuntos
Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Peptídeos/farmacologia , Animais , Antígenos CD34/metabolismo , Biomarcadores , Proteínas de Transporte , Técnicas de Cultura de Células , Diferenciação Celular , Autorrenovação Celular , Células Cultivadas , Imunofluorescência , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunofenotipagem , Camundongos , Ligação Proteica
11.
Int J Mol Sci ; 22(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918699

RESUMO

Renal fibrosis is a complex disorder characterized by the destruction of kidney parenchyma. There is currently no cure for this devastating condition. Extracellular vesicles (EVs) are membranous vesicles released from cells in both physiological and diseased states. Given their fundamental role in transferring biomolecules to recipient cells and their ability to cross biological barriers, EVs have been widely investigated as potential cell-free therapeutic agents. In this review, we provide an overview of EVs, focusing on their functional role in renal fibrosis and signaling messengers responsible for EV-mediated crosstalk between various renal compartments. We explore recent findings regarding the renoprotective effect of EVs and their use as therapeutic agents in renal fibrosis. We also highlight advantages and future perspectives of the therapeutic applications of EVs in renal diseases.


Assuntos
Vesículas Extracelulares/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Animais , Micropartículas Derivadas de Células/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Exossomos/metabolismo , Sangue Fetal/citologia , Fibroblastos/metabolismo , Fibrose , Humanos , Nefropatias/etiologia , Células-Tronco Mesenquimais/metabolismo
12.
Nutrients ; 13(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808763

RESUMO

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC-FID). Intrauterine transfer percentages for each fatty acid were calculated as follows: ((cord blood fatty acid level/maternal blood fatty acid level) × 100). Kruskal-Wallis tests were used to compare transfer percentages between maternal fatty acid tertile groups. A p-value < 0.05 was considered significant. There were statistically significant differences in intrauterine transfer percentages of arachidonic acid (AA) (64% vs. 65% vs. 45%, p = 0.02), eicosapentaenoic acid (EPA) (41% vs. 19% vs. 17%, p = 0.03), and total fatty acids (TFA) (27% vs. 26% vs. 20%, p = 0.05) between maternal plasma fatty acid tertiles. Intrauterine transfer percentages of AA, EPA, and TFA were highest in the lowest tertile of respective maternal fatty acid concentration. These findings may indicate that fatty acid transfer to the fetus is prioritized during gestation even during periods of maternal nutritional inadequacy.


Assuntos
Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/metabolismo , Sangue Fetal/metabolismo , Desenvolvimento Fetal , Ácido Araquidônico/sangue , Ácido Araquidônico/metabolismo , Estudos Transversais , Ácido Eicosapentaenoico/análogos & derivados , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3 , Feminino , Feto , Humanos , Lactente , Ácido Linoleico , Masculino , Placenta/metabolismo , Gravidez
13.
Sci Total Environ ; 783: 147035, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-33872906

RESUMO

Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood. The genes annotated to the CpGs positively associated with MEHP levels were enriched for pathways related to metabolism, the endocrine system, and signal transduction. Among them, methylation levels of CpGs involved in metabolism were inversely associated with the offspring's ponderal index (PI). Further, clustering and mediation analyses suggested that multiple increased methylation changes may jointly mediate the association of DEHP exposure in utero with the offspring's PI at birth. Although further studies are required to assess the impact of these changes, this study suggests that differential DNA methylation may link phthalate exposure in utero to fetal growth and further imply that DNA methylation has predictive value for the offspring's obesity.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Criança , Saúde da Criança , Metilação de DNA , Dietilexilftalato/toxicidade , Epigenoma , Feminino , Sangue Fetal , Desenvolvimento Fetal , Humanos , Recém-Nascido , Ácidos Ftálicos/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética
14.
Int J Mol Sci ; 22(5)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801461

RESUMO

Osteoarthritis (OA) is a significant cause of pain in both humans and horses with a high socio-economic impact. The horse is recognized as a pertinent model for human OA. In both species, regenerative therapy with allogeneic mesenchymal stem cells (MSCs) appears to be a promising treatment but, to date, no in vivo studies have attempted to compare the effects of different cell sources on the same individuals. The objective of this study is to evaluate the ability of a single blinded intra-articular injection of allogeneic bone-marrow (BM) derived MSCs and umbilical cord blood (UCB) derived MSC to limit the development of OA-associated pathological changes compared to placebo in a post-traumatic OA model applied to all four fetlock joints of eight horses. The effect of the tissue source (BM vs. UCB) is also assessed on the same individuals. Observations were carried out using clinical, radiographic, ultrasonographic, and magnetic resonance imaging methods as well as biochemical analysis of synovial fluid and postmortem microscopic and macroscopic evaluations of the joints until Week 12. A significant reduction in the progression of OA-associated changes measured with imaging techniques, especially radiography, was observed after injection of bone-marrow derived mesenchymal stem cells (BM-MSCs) compared to contralateral placebo injections. These results indicate that allogeneic BM-MSCs are a promising treatment for OA in horses and reinforce the importance of continuing research to validate these results and find innovative strategies that will optimize the therapeutic potential of these cells. However, they should be considered with caution given the low number of units per group.


Assuntos
Artrite Experimental/prevenção & controle , Medula Óssea/crescimento & desenvolvimento , Sangue Fetal/citologia , Células-Tronco Mesenquimais/citologia , Osteoartrite/prevenção & controle , Líquido Sinovial/citologia , Animais , Artrite Experimental/etiologia , Artrite Experimental/patologia , Feminino , Cavalos , Injeções Intra-Articulares , Masculino , Transplante de Células-Tronco Mesenquimais , Osteoartrite/etiologia , Osteoartrite/patologia
15.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807258

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells.


Assuntos
Células Eritroides/classificação , Células Eritroides/metabolismo , MicroRNAs/genética , Adulto , Fatores Etários , Diferenciação Celular/genética , Linhagem Celular , Eritropoese/genética , Sangue Fetal/citologia , Hemoglobina Fetal/genética , Feto/metabolismo , Humanos , RNA Mensageiro/genética , Fatores de Transcrição , gama-Globinas/genética
16.
Nutrients ; 13(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33808021

RESUMO

Zinc and iron deficiencies among infants aged under 6 months may be related with nutrient store at birth. This study aimed to investigate the association between zinc and iron stores at birth with maternal nutritional status and intakes during pregnancy. 117 pregnant women were enrolled at the end of second trimester and followed until delivery. Clinical data during pregnancy, including pre-pregnancy body mass index (BMI) and at parturition were collected from medical record. Zinc and iron intakes were estimated from a food frequency questionnaire. Serum zinc and ferritin were determined in maternal blood at enrollment and cord blood. Mean cord blood zinc and ferritin were 10.8 ± 2.6 µmol/L and 176 ± 75.6 µg/L, respectively. Cord blood zinc was associated with pre-pregnancy BMI (adj. ß 0.150; p = 0.023) and serum zinc (adj. ß 0.115; p = 0.023). Cord blood ferritin was associated with pre-pregnancy BMI (adj. ß -5.231; p = 0.009). Cord blood zinc and ferritin were significantly higher among those having vaginal delivery compared to cesarean delivery (adj. ß 1.376; p = 0.007 and 32.959; p = 0.028, respectively). Maternal nutritional status and mode of delivery were significantly associated with zinc and iron stores at birth. Nutrition during preconception and pregnancy should be ensured to build adequate stores of nutrients for infants.


Assuntos
Parto Obstétrico/estatística & dados numéricos , Ferro/sangue , Estado Nutricional , Parto/sangue , Zinco/sangue , Adulto , Índice de Massa Corporal , Parto Obstétrico/métodos , Inquéritos sobre Dietas , Feminino , Ferritinas/sangue , Sangue Fetal/química , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Segundo Trimestre da Gravidez/sangue
17.
BMC Pregnancy Childbirth ; 21(1): 279, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832462

RESUMO

BACKGROUND: Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth. METHODS: A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. RESULTS: The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency. CONCLUSIONS: Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.


Assuntos
Sangue Fetal/química , Recém-Nascido/sangue , Gravidez de Gêmeos/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Adulto , China/epidemiologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Projetos Piloto , Gravidez , Estudos Prospectivos , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Adulto Jovem
18.
BMC Pregnancy Childbirth ; 21(1): 283, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836691

RESUMO

BACKGROUND: Telomere length (TL) is variable at birth and is inversely associated with body mass index (BMI) in adulthood. A growing number of evidences suggested that a higher maternal pre-pregnancy BMI results in adverse offspring health outcomes, especially shorter newborn TL. However, a newborn's genetic endowment is equally derived from both parents, the association between parental pre-pregnancy BMI and newborn TL has been rarely discussed. We aimed to determine the association between parental pre-pregnancy BMI and newborn TL. METHODS: A total of 1082 parent-newborn pairs were recruited from the Guangxi Zhuang Birth Cohort (GZBC). TL in cord blood was measured using quantitative real-time polymerase chain reaction (qPCR) and expressed as the ratio of telomere copy number to single-copy gene number (T/S). A series of linear regressions were performed to assess the associations between parental pre-pregnancy BMI and newborn TL. RESULTS: Mothers who were overweight before pregnancy had significantly shorter cord blood telomere length in their newborns than those who were normal weight before pregnancy [percentage change: - 7.96% (95% CI: - 14.49 to - 0.69%; P = 0.032)]. Further analysis of the combined effects of parental weight status on newborn TL showed that TL was significantly shortened among newborns whose mothers were overweight and fathers were of healthy weight when compared with those whose mothers and fathers were both of normal weight [percentage change: - 8.38% (95% CI: - 15.47 to - 0.92%; P = 0.028)]. Subgroup analysis indicated these effects were more pronounced among male newborns and those whose paternal age < 31 years or maternal age ≥ 28 years at delivery. CONCLUSIONS: Maternal pre-pregnancy overweight, but not paternal pre-pregnancy overweight is associated with shorter newborn TL. Weight control in reproductive women and effective healthy weight management before pregnancy may be of particular benefit for improving longevity and life quality of offspring.


Assuntos
Herança Materna , Sobrepeso/epidemiologia , Telômero/genética , Adulto , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Pai/estatística & dados numéricos , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Sobrepeso/diagnóstico , Sobrepeso/genética , Herança Paterna , Gravidez , Fatores de Risco , Homeostase do Telômero/genética , Adulto Jovem
19.
BMC Pregnancy Childbirth ; 21(1): 303, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858365

RESUMO

BACKGROUND: Exosomal circular RNAs (circRNAs) are emerging as important regulators of physiological development and disease pathogenesis. However, the roles of exosomal circRNAs from umbilical cord blood in preeclampsia (PE) occurrence remains poorly understood. METHODS: We used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. Bioinformatics analysis was conducted to further predict the potential effects of the differentially expressed circRNAs and their interactions with miRNAs. RESULTS: According to the microarray data, we identified 143 significantly up-regulated circRNAs and 161 significantly down-regulated circRNAs in umbilical cord blood exosomes of PE patients compared with controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses showed that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which play important roles in PE development. Moreover, pathway network was constructed to reveal the key pathways in PE, such as PI3K-Akt signaling pathway. Further circRNA/miRNA interactions analysis demonstrated that most exosomal circRNAs had miRNA binding sites, and some miRNAs were associated with PE. CONCLUSIONS: Our results highlight the importance of exosomal circRNAs in the pathogenesis of PE and lay a foundation for extensive studies on the role of exosomal circRNAs in PE development.


Assuntos
Exossomos/metabolismo , Sangue Fetal/metabolismo , Pré-Eclâmpsia/metabolismo , RNA Circular/metabolismo , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez , Regulação para Cima
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