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1.
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
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(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
4.
Nutr Metab Cardiovasc Dis ; 31(6): 1791-1797, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023181

RESUMO

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM), hyperglycemia diagnosed during pregnancy, is one of the most common medical complications of pregnancy, treated primarily by diet and pharmacotherapy, if indicated. It is well-established that GDM increases the risk of adverse pregnancy outcomes and long-term complications in mothers and infants. Galectin-3 (Gal-3) is important in processes of cell growth, differentiation, inflammation, and fibrosis. We evaluated Gal-3 expression in pregnancies complicated by GDM as a parameter that might explain how GDM influences early onset of future complications. METHODS AND RESULTS: Forty-four women with GDM and 40 with normal pregnancy (NP) were recruited during delivery admission. Blood samples were obtained from parturients and umbilical cords blood, as well as placental tissue for analysis. Gal-3 mRNA expression was increased in maternal blood samples and placental tissue of women with GDM compared to NP. In GDM, Gal-3 mRNA was decreased in cord blood compared to maternal blood and placental tissue. Gal-3 GDM placental protein expression was increased compared to NP. Immunostaining revealed that Gal-3 is upregulated in GDM placental extravillous trophoblast. ELISA of Gal-3 maternal serum levels between GDM and NP were similar. CONCLUSION: Gal-3 is strongly expressed at molecular levels (mRNA and protein expression) in GDM maternal blood and placental tissue, and decreased in cord blood. These findings highlight the role of the placenta in protecting the fetus from potential Gal-3 damage. Gal-3 expression at mRNA and protein levels might be influenced by diabetes, even if blood glucose is balanced by medication or diet.


Assuntos
Proteínas Sanguíneas/metabolismo , Diabetes Gestacional/metabolismo , Galectinas/metabolismo , Placenta/metabolismo , Adulto , Biomarcadores/metabolismo , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Feminino , Sangue Fetal/metabolismo , Galectinas/sangue , Galectinas/genética , Humanos , Troca Materno-Fetal , Gravidez , Regulação para Cima
5.
Environ Health ; 20(1): 35, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794901

RESUMO

BACKGROUND: Up to now, 3 epidemiological studies have shown clear inverse associations between prenatal acrylamide exposure and birth size. In addition to studying the association between acrylamide and birth size, we investigated the interaction between acrylamide and polymorphisms in acrylamide-metabolising genes, with the aim of probing the causality of the inverse relationship between acrylamide and fetal growth. METHODS: We investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels (AA-Hb and GA-Hb) in cord blood) and birth weight, length and head circumference in 443 newborns of the ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort. In addition, we studied interaction with single nucleotide polymorphisms (SNPs) in CYP2E1, EPHX1 and GSTP1, using multiple linear regression analysis. RESULTS: Among all neonates, the body weight, length and head circumference of neonates in the highest quartile was - 101 g (95% CI: - 208, 7; p for trend = 0.12), - 0.13 cm (95% CI: - 0.62, 0.36; p for trend = 0.69) and - 0.41 cm (- 0.80, - 0.01; p for trend = 0.06) lower, respectively, compared to neonates in the lowest quartile of AA-Hb in cord blood, For GA-Hb, the corresponding effect estimates were - 222 g (95% CI: - 337, - 108; p for trend = 0.001), - 0.85 (95% CI: - 1.38, - 0.33; p for trend = 0.02) and - 0.55 (95% CI: - 0.98, - 0.11; p for trend = 0.01), respectively. The associations for GA-Hb were similar or stronger in newborns of non-smoking mothers. There was no statistically significant interaction between acrylamide exposure and the studied genetic variations but there was a trend of stronger inverse associations with birth weight and head circumference among newborns with homozygous wildtypes alleles for the CYP2E1 SNPS and with variant alleles for a GSTP1 SNP (rs1138272). CONCLUSIONS: Prenatal dietary acrylamide exposure, specifically in the form of its metabolite glycidamide, was inversely associated with birth weight, length and head circumference. The interaction pattern with SNPs in CYP2E1, although not statistically significant, is an indication for the causality of this association. Other studies are needed to corroborate this finding.


Assuntos
Acrilamida/sangue , Peso ao Nascer , Citocromo P-450 CYP2E1/genética , Epóxido Hidrolases/genética , Sangue Fetal/metabolismo , Glutationa S-Transferase pi/genética , Exposição Materna , Troca Materno-Fetal , Acrilamida/metabolismo , Adulto , Compostos de Epóxi/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Recém-Nascido , Masculino , Polimorfismo de Nucleotídeo Único , Gravidez
6.
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
7.
Toxicol Appl Pharmacol ; 422: 115554, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33910022

RESUMO

Clotrimazole is a non-prescription and broad-spectrum antifungal drug sold under brand names such as Canesten® and Lotrimin®. It is used to treat different types of fungal infections, from oral thrush to athlete's foot and vaginal mycosis. The level of exposure to clotrimazole is uncertain, as the exact usage amongst self-medicating patients is unclear. Recent studies have raised potential concern about the unsupervised use of clotrimazole during pregnancy, especially since it is a potent inhibitor of CYP enzymes of the steroidogenesis pathway. To address some of these concerns, we have assessed the effects of intrauterine exposure to clotrimazole on developing rat fetuses. By exposing pregnant rats to clotrimazole 25 or 75 mg/kg bw/day during gestation days 7-21, we obtained internal fetal concentrations close to those observed in humans. These in vivo data are in strong agreement with our physiologically-based pharmacokinetic (PBK)-modelled levels. At these doses, we observed no obvious morphological changes to the reproductive system, nor shorter male anogenital distance; a well-established morphometric marker for anti-androgenic effects in male offspring. However, steroid hormone profiles were significantly affected in both maternal and fetal plasma, in particular pronounced suppression of estrogens was seen. In fetal testes, marked up-concentration of hydroxyprogesterone was observed, which indicates a specific action on steroidogenesis. Since systemic clotrimazole is rapidly metabolized in humans, relevant exposure levels may not in itself cause adverse changes to the reproductive systems. Its capacity to significantly alter steroid hormone concentrations, however, suggests that clotrimazole should be used with caution during pregnancy.


Assuntos
Antifúngicos/toxicidade , Clotrimazol/toxicidade , Disruptores Endócrinos/toxicidade , Feto/efeitos dos fármacos , Hormônios Esteroides Gonadais/sangue , Animais , Antifúngicos/sangue , Antifúngicos/farmacocinética , Biomarcadores/sangue , Clotrimazol/sangue , Clotrimazol/farmacocinética , Disruptores Endócrinos/sangue , Disruptores Endócrinos/farmacocinética , Estrogênios/sangue , Feminino , Sangue Fetal/metabolismo , Feto/metabolismo , Idade Gestacional , Humanos , Hidroxiprogesteronas/sangue , Masculino , Exposição Materna , Gravidez , Ratos Sprague-Dawley , Medição de Risco , Especificidade da Espécie , Toxicocinética
8.
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
9.
Histochem Cell Biol ; 156(1): 59-67, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33725198

RESUMO

The foetal bovine serum (FBS) concentration could influence functional parameters of IPEC-J2 cells. IPEC-J2 is a non-transformed continuous epithelial cell line that represents an established in vitro model to study porcine gut inflammation and alterations of intestinal integrity. This cell line also represents a good translational model thanks to the high similitudes between pig and human gastrointestinal tract. With the aim to assess if the FBS-dependent functional variations are linked to the bioenergetic aspects, the addition of 5% and 10% FBS in the IPEC-J2 culture medium were tested. Doubling time and TEER measurement indicated that cells cultured at higher FBS dose grow faster and as a more compact monolayer. 10% FBS increases ATP production and mitochondrial oxidative phosphorylation (OxPhos) and does not affect glycolysis. Both at 5% and 10% FBS ATP production mainly comes from OxPhos and FBS concentration does not affect the cell respiration bioenergetic parameters. Noteworthy, IPEC-J2 treated with 5% and 10% FBS have a metabolic potential since both OxPhos and glycolysis increase by > 100% and < 50%, respectively in comparison with baseline metabolism. Moreover, glucose, fatty acids and glutamine constitute the preferred metabolic fuel for mitochondrial respiration at both FBS conditions tested. Accordingly, the cells flexibility to oxidize these substrates shows that IPEC-J2 mitochondria cannot maintain the basal ATP production without oxidizing all the substrates available irrespective of FBS concentration. To sum up, in IPEC-J2 cells OxPhos increases with the FBS-stimulated functional physiological parameters to fulfil ATP requirements.


Assuntos
Trifosfato de Adenosina/biossíntese , Sangue Fetal/metabolismo , Trifosfato de Adenosina/sangue , Animais , Bovinos , Células Cultivadas , Suínos
10.
Biomed Res Int ; 2021: 6380141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708990

RESUMO

The aim of this study was to investigate the therapeutic efficacy and safety of transplanting human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the treatment of cartilage injury. First, the articular cartilage defect model in rabbits was constructed. Then, the identified hUCB-MSCs and rabbit bone marrow stem cells (rBM-MSCs) were transplanted into the bone defect, respectively, and the cartilage repair effect was observed by hematoxylin-eosin (HE) staining and immunohistochemistry. Besides, the glycosaminoglycan (GAG) content and biomechanics of the restoration area were also evaluated. In our study, hUCB-MSCs and rBM-MSCs exhibited typical MSC characteristics, with positive expressions of CD73, CD105, and CD90 and negative for CD45, CD34, CD14, and HLA-DR. After the transplantation of hUCB-MSCs and rBM-MSCs, the overall quality of cartilage tissue was significantly improved, and the recipients did not show significant side effects in general. However, the expression of matrix metalloproteinase-13 (MMP-13) in the de novo tissues of the hUCB-MSCs and rBM-MSCs groups was both increased, indicating that the novel tissues may have some potential osteoarthritic changes. In conclusion, our results suggest the therapeutic effect of hUCB-MSCs transplantation in cartilage regeneration, providing a promising future in the clinical treatment of cartilage injury.


Assuntos
Antígenos de Diferenciação/metabolismo , Cartilagem Articular , Sangue Fetal/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Osteoartrite , Animais , Cartilagem Articular/lesões , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Xenoenxertos , Humanos , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/terapia , Coelhos
11.
Biomed Res Int ; 2021: 6685605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708992

RESUMO

Mesenchymal stem cells (MSCs) were shown to have potential therapeutic effects for treatment of liver fibrosis, and dysregulated expression of microRNAs (miRNAs) played a pivotal role in the pathogenesis of liver fibrosis by regulating their downstream target genes. However, the mechanism by which MSCs affect the progression of liver fibrosis by regulating miRNA expression remains unclear. Here, we investigated whether human umbilical cord MSCs (HUC-MSCs) attenuated hepatic fibrosis by regulating miR-455-3p and its target gene. Significantly upregulated miRNA (miR-455-3p) was screened out by GEO datasets analysis and coculture HUC-MSCs with hepatic stellate cell (HSC) LX-2 cells. p21-activated kinase-2 (PAK2) was forecasted to be the target gene of miR-455-3p by bioinformatics analyses and confirmed by luciferase reporter assay. HUC-MSCs were transplanted into mice with carbon tetrachloride- (CCl4-) induced liver fibrosis, the result showed that HUC-MSC transplantation significantly ameliorated the severity of CCl4-induced liver fibrosis, attenuated collagen deposition, improved liver function by reducing the expression of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, upregulated miR-455-3p, and suppressed PAK2 expression of liver tissue in mice. Taken together, our study suggests that HUC-MSCs inhibit the activation of HSCs and mouse CCl4-induced liver fibrosis by upregulation of miR-455-3p through targeting PAK2.


Assuntos
Sangue Fetal/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/biossíntese , Regulação para Cima , Quinases Ativadas por p21/sangue , Animais , Linhagem Celular , Xenoenxertos , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/terapia , Masculino , Camundongos
12.
Artigo em Inglês | MEDLINE | ID: mdl-33669328

RESUMO

Childhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have been previously examined as biomarkers predicting future obesity. We conducted a systematic review looking at the association between cord blood leptin and adiponectin with adiposity up to 5 years of age. A literature review was performed between January 1994 and August 2020 using two bibliographic databases (Medline/Pubmed and EMBASE) and was registered on PROSPERO (CRD42017069024). Studies using skinfold thickness and direct methods of assessing body composition in full term neonates were considered. Partial correlation and multiple regression models were used to present the results. Meta-analysis was performed, were possible, using a random effects model. Cochran's Q test was used to assess heterogeneity and I2 statistics to calculate the percentage of variation across studies. The potential for publication bias was assessed using funnel plots. Data from 22 studies were retrieved and reviewed by two independent reviewers. Cord blood leptin was positively associated with adiposity at birth (r = 0.487; 95% CI: 0.444, 0.531) but was inversely related to adiposity up to 3 years of age. The association was not sustained at 5 years. There was a weak positive association between adiponectin in cord blood and adiposity at birth (r = 0.201; 95% CI: 0.125, 0.277). No correlation was found between cord blood adiponectin in young children, but data were limited. This review supports that cord blood leptin and adiponectin are associated with adiposity at birth. The results of this study provide insight into the role of adipocytokines at birth on future metabolic health and their potential use as risk stratification tools.


Assuntos
Adipocinas , Sangue Fetal , Adipocinas/metabolismo , Adiponectina/metabolismo , Adiposidade , Composição Corporal , Criança , Pré-Escolar , Sangue Fetal/metabolismo , Humanos , Recém-Nascido , Leptina/metabolismo
13.
Methods Mol Biol ; 2269: 107-124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33687675

RESUMO

Umbilical cord blood of neonates is a precious source for many fields of research because of distinct unique features combined with easy accessibility at the time of birth. The number of applications are vast with an emphasis in the field of stem cell therapy and regenerative medicine since cord blood contains relatively large numbers of pluripotent cells. This chapter provides a protocol for developing an autologous co-culture of endothelial-like cells and peripheral blood mononuclear cells from umbilical cord blood of premature born babies and describes an experimental setting to investigate inflammatory processes that are a cornerstone of pathophysiology in the developing organs of preterm born babies.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Sangue Fetal/metabolismo , Leucócitos Mononucleares/metabolismo , Técnicas de Cocultura , Células Progenitoras Endoteliais/patologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Leucócitos Mononucleares/patologia , Masculino
14.
Diabetes Res Clin Pract ; 173: 108702, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33609619

RESUMO

AIMS: This research aimed to investigate the effects of high glucose (HG) on the innate immunity of podocytes and diabetic nephropathy (DN) mice via Toll like receptor (TLR) signaling, and explore the protective effectsof human umbilical cord mesenchymal stem cells (HUC-MSCs) on this process. METHODS: HUC-MSCs obtained from human umbilical cord were cocultured with podocytes and transplanted into DN mice. Flow cytometry, CCK-8assay, ELISA, western blot analysis, periodicacid-schiff, masson, immunohistochemistry and immunofluorescence staining was used to detect the inflammation, TLR signaling, physical, biochemical and morphological parameters in podocytes and DN mice. RESULTS: HG reduced the viability of podocytes, activated TLR2 and TLR4 signaling pathway and increased the expression of inflammatory cytokines such as IL-6, IL-1ß, TNF-α, and MCP-1 in podocytes and DN mice. However, HUC-MSCs decreased the inflammation and restrained the TLR signaling pathway caused by HG in vitro and in vivo. Furthermore the rhHGF decreased the expression of TLR2 and TLR4 while the blockade of HGF increased the expression of TLR2 and TLR4 in podocytes. CONCLUSIONS: HUC-MSCs have benefits to the podocytes under HG and the progression of DN by inhibiting TLR signaling pathway and depressing the inflammation. HUC-MSCs may be a therapeutic strategy for treating patients with DN.


Assuntos
Sangue Fetal/metabolismo , Glucose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Podócitos/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Transdução de Sinais
15.
Transfusion ; 61(4): 1080-1092, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33629748

RESUMO

BACKGROUND: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. STUDY DESIGN AND METHODS: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. RESULTS: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). CONCLUSION: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.


Assuntos
Teste de Coombs/estatística & dados numéricos , Eritroblastose Fetal/imunologia , Recém-Nascido/imunologia , Medicina Transfusional/normas , Sistema ABO de Grupos Sanguíneos/imunologia , Anticorpos Anti-Idiotípicos/análise , Bilirrubina/análise , Canadá/epidemiologia , Teste de Coombs/normas , Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/epidemiologia , Eritrócitos/imunologia , Sangue Fetal/imunologia , Sangue Fetal/metabolismo , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/diagnóstico , Lactente , Recém-Nascido/sangue , Guias de Prática Clínica como Assunto/normas , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia
16.
Diabetes Res Clin Pract ; 174: 108690, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33549677

RESUMO

BACKGROUND: Fetal exposure to maternal GDM increases offspring risk for adult-onset metabolic syndromes. Epigenetic modifications such as DNA methylation are modulators for fetal metabolic programming and susceptibility to adult-onset disease. This study investigates genome-wide DNA methylation in GDM exposed cord blood and placenta. METHODS: Oral glucose tolerance testing between 24 and 28 weeks of pregnancy was used to determine severity of glucose intolerance. We measured DNA methylation (DNAm) using the Illumina Infinium 450 K array in 42 fetal cord blood and 36 placenta samples. RESULTS: We identified 662 and 99 CpG sites in GDM placenta and cord blood, respectively at p-value <0.01 and a methylation difference >5% after adjustment for confounders. Annotated sites for AHRR and PTPRN2 were common to cord blood and placenta. Adding published GDM cord blood DNAm data we segregated patients based on treatment (Diet Only vs. +Insulin) and identified altered CpG sites to be unique to each GDM treatment group. CONCLUSION: Consistency in findings with other studies provides evidence for the role of DNAm in placental and fetal responses to hyperglycemia. However, segregating DNAm analysis of GDM samples based on treatment may help delineate whether observed DNAm alterations are reflective of adaptive responses or treatment effects in utero.


Assuntos
Metilação de DNA/genética , Diabetes Gestacional/sangue , Sangue Fetal/metabolismo , Placenta/metabolismo , Adulto , Diabetes Gestacional/genética , Feminino , Humanos , Gravidez
17.
Diabetes ; 70(4): 854-866, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33431374

RESUMO

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.


Assuntos
Metilação de DNA/fisiologia , Sangue Fetal/metabolismo , Obesidade/genética , Peso ao Nascer/fisiologia , Composição Corporal/genética , Composição Corporal/fisiologia , Índice de Massa Corporal , Metilação de DNA/genética , Exercício Físico/fisiologia , Feminino , Humanos , Estilo de Vida , Gravidez , Gestantes
18.
Blood Cells Mol Dis ; 88: 102536, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33450539

RESUMO

In a two-part process, we assessed elements of the principal hormonal pathway regulating iron homeostasis in human neonates. Part 1: Quantifying erythropoietin (Epo), erythroferrone (ERFE), hepcidin, and relevant serum and erythrocytic iron-related metrics in umbilical cord blood from term (n = 13) and preterm (n = 10) neonates, and from neonates born to mothers with diabetes and obesity (n = 13); Part 2: Quantifying serum Epo, ERFE, and hepcidin before and following darbepoetin administration. Part 1: We measured Epo, ERFE and hepcidin in all cord blood samples. Epo and ERFE levels did not differ between the three groups. Preterm neonates had the lowest hepcidin levels, while neonates born to diabetic women with a very high BMI had the lowest ferritin and RET-He levels. Part 2: Following darbepoetin dosing, ERFE levels generally increased (p < 0.05) and hepcidin levels generally fell (p < 0.05). Our observations suggest that the Epo/ERFE/hepcidin axis is intact in the newborn period.


Assuntos
Eritropoetina/sangue , Hepcidinas/sangue , Hormônios Peptídicos/sangue , Transdução de Sinais , Eritropoetina/metabolismo , Feminino , Sangue Fetal/metabolismo , Hepcidinas/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Obesidade/sangue , Obesidade/metabolismo , Hormônios Peptídicos/metabolismo , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/metabolismo , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/metabolismo , Nascimento Prematuro/sangue , Nascimento Prematuro/metabolismo
19.
PLoS One ; 16(1): e0242978, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33493154

RESUMO

Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid-histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.


Assuntos
Ordem de Nascimento , Parto Obstétrico , Sangue Fetal/metabolismo , Hipersensibilidade/epidemiologia , Fenômenos Fisiológicos da Nutrição Materna , Metaboloma , População Rural , Caracteres Sexuais , Adulto , Criança , Pré-Escolar , Dieta , Fazendas , Feminino , Humanos , Hipersensibilidade/diagnóstico , Recém-Nascido , Masculino , Gravidez , Suécia/epidemiologia
20.
Environ Res ; 195: 110767, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33515580

RESUMO

BACKGROUND: Prenatal lead exposure has been reported to affect infant growth and nervous system development, as well as to influence DNA methylation. We conducted an epigenome-wide association study to identify associations between prenatal lead exposure and cord blood DNA methylation in Korean infants. METHODS: Cord blood samples were assayed with the Illumina HumanMethylationEPIC BeadChip kits, and maternal blood lead levels during early and late pregnancy, as well as cord blood lead level, were measured. The association between CpG methylation and lead level was analyzed using the limma package, with adjusting for infant sex, maternal pre-pregnancy body mass index, and estimated leukocyte composition. RESULTS: Among 364 blood samples (182 males and 182 females), those for which maternal and cord blood lead concentrations during early and later pregnancy was known were used for analysis. Maternal lead concentration in blood during early pregnancy was significantly associated with the methylation status of specific positions. After data stratification by infant sex, we found that, in males, the level of maternal blood lead was associated with 18 CpG sites during early pregnancy, and with one CpG site near the NBAS gene, during late pregnancy. In female samples, there was no significant association between DNA methylation and lead concentrations. CONCLUSIONS: Prenatal lead exposure was associated with altered, gender-specific patterns of DNA methylation in Korean infants.


Assuntos
Expossoma , Efeitos Tardios da Exposição Pré-Natal , Ilhas de CpG , Metilação de DNA , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Chumbo/metabolismo , Chumbo/toxicidade , Masculino , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , República da Coreia
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