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1.
Biomolecules ; 12(4)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35454129

RESUMO

Physiological low oxygen (O2) concentration (<5%) favors erythroid development ex vivo. It is known that low O2 concentration, via the stabilization of hypoxia-induced transcription factors (HIFs), intervenes with Notch signaling in the control of cell fate. In addition, Notch activation is implicated in the regulation of erythroid differentiation. We test here if the favorable effects of a physiological O2 concentration (3%) on the amplification of erythroid progenitors implies a cooperation between HIFs and the Notch pathway. To this end, we utilized a model of early erythropoiesis ex vivo generated from cord blood CD34+ cells transduced with shHIF1α and shHIF2α at 3% O2 and 20% O2 in the presence or absence of the Notch pathway inhibitor. We observed that Notch signalization was activated by Notch2R-Jagged1 ligand interaction among progenitors. The inhibition of the Notch pathway provoked a modest reduction in erythroid cell expansion and promoted erythroid differentiation. ShHIF1α and particularly shHIF2α strongly impaired erythroid progenitors' amplification and differentiation. Additionally, HIF/NOTCH signaling intersects at the level of multipotent progenitor erythroid commitment and amplification of BFU-E. In that, both HIFs contribute to the expression of Notch2R and Notch target gene HES1. Our study shows that HIF, particularly HIF2, has a determining role in the early erythroid development program, which includes Notch signaling.


Assuntos
Células Precursoras Eritroides , Eritropoese , Diferenciação Celular , Células Cultivadas , Células Precursoras Eritroides/metabolismo , Eritropoese/genética , Sangue Fetal , Oxigênio/metabolismo
2.
Biochem Biophys Res Commun ; 608: 14-22, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35381424

RESUMO

The characteristics of neonatal immune cells display intrinsic differences compared with adult immune cells. Therefore, a comprehensive analysis of key gene expression regulation is required to understand the response of the human fetal immune system to infections. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) to systematically profile umbilical cord blood (UCB) nucleated cells and peripheral blood mononuclear cells (PBMCs) to identify their composition and differentially expressed genes. The immune cells in neonatal UCB demonstrated the expression of key genes, such as HBG2, NFKBIA, JUN, FOS, and TNFAIP3. In contrast, natural killer and T cells, which are constituents of adult PBMCs, exhibited high cytotoxic gene expression. Furthermore, we obtained similar results from the data of scATAC-seq by identifying the status of chromatin accessibility of key genes. Therefore, scRNA-seq and scATAC-seq of neonatal UCB nucleated cells and adult PBMCs could serve as an invaluable resource for elucidating the regulatory mechanisms of responses of distinct immune cell types and further identifying the differences between neonatal and adult immune responses to predict the potential underlying mechanism for neonatal immune tolerance.


Assuntos
Sangue Fetal , Análise de Célula Única , Adulto , Cromatina/metabolismo , Humanos , Tolerância Imunológica/genética , Recém-Nascido , Leucócitos Mononucleares/metabolismo , Análise de Célula Única/métodos , Transposases/genética
3.
Sci Rep ; 12(1): 5894, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393444

RESUMO

Motor neuron diseases such as spinal cord injuries and amyotrophic lateral sclerosis are known as the most common disorders worldwide. Using stem cells (e.g., human umbilical cord blood mesenchymal stem cells) is currently a potent medical approach for modulating the impact of neural damages and regeneration of spinal cord injuries. MicroRNAs (miRNA) are taken into account as principal regulators during differentiation. The miRNAs play a significant role in stem cell self-renewal and fate determination. There are few studies on how miRNAs regulate neural differentiation in stem cells. The purpose of this study is to explore miRNA profiles of CB-MSCs during differentiation into motor neuron-like cells. Human CB-MSCs were isolated and characterized using flow cytometry. Cell differentiation has been induced by combining retinoic acid (RA) and sonic hedgehog (Shh) in a two-step protocol for 14 days. Then, cell differentiation was confirmed by immunocytochemistry and flow cytometry. The miRNA was analyzed using Illumina/Solexa sequencing platform. In this regard, three libraries were prepared to investigate the effect of these two biological morphogens on the miRNA profile of the differentiating cells. These libraries were Control (non-treated CB-MSCs), Test 1 (RA + /Shh +), and Test 2 (RA-/Shh-). Quantitative RT-PCR was employed to verify miRNA expression. CB-MSCs were spindle-shaped in morphology, and they did not express hematopoietic markers. After differentiation, the cells expressed motor neuron markers (i.e., Islet-1, SMI-32, and ChAT) at the protein level after 14 days. The analysis of miRNA sequencing demonstrated a significant up-regulation of miR-9-5p and miR-324-5p in Test 1 (RA + /Shh +). Also, there is a considerable down-regulation of mir-137 and let-7b in Test 2 (RA-/Shh-). These results have been obtained by comparing them with the Control library. Indeed, they were responsible for neuron and motor neuron differentiation and suppression of proliferation in neural progenitor cells. Furthermore, significant up-regulation was detected in some novel microRNAs involved in cholinergic, JAK-STAT, and Hedgehog and MAPK signaling pathways. CB-MSCs are potent to express motor neuron markers. This procedure has been performed by developing a two-week protocol and employing Shh and RA. The miRNA profile analysis showed a significant up-regulation in the expression of some miRs involved in neuron differentiation and motor neuron maturation. MiR-9-5p and miR-324-5p were up-regulated at the early stage of differentiation. Also, miR-137 and miR-let-7b were downregulated in the absence of RA and Shh. Furthermore, several novel miRNAs involved in cholinergic, Hedgehog, MAPK, and JAK-STAT signaling pathways have been detected. However, further studies are still necessary to validate their functions during motor neuron generation and maturation.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Traumatismos da Medula Espinal , Diferenciação Celular , Colinérgicos/metabolismo , Sangue Fetal/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , MicroRNAs/metabolismo , Neurônios Motores/metabolismo , Traumatismos da Medula Espinal/metabolismo , Tretinoína/metabolismo , Tretinoína/farmacologia
4.
Hematology ; 27(1): 476-487, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35413231

RESUMO

OBJECTIVE: The interplay between intrinsic and extrinsic elements involved in the physiology of hematopoietic cells is not completely understood. In the present study, we analyzed the transcriptional profiles of human cord blood-derived hematopoietic stem cells (HSCs), as well as myeloid (MPCs) and erythroid (EPCs) progenitors, and assessed their proliferation and expansion kinetics in vitro. METHODS: All cell populations were obtained by cell-sorting, and were cultured in liquid cultures supplemented with different cytokine combinations. Their gene expression profiles were determined by RNA microarrays right after cell-sorting, before culture. RESULTS: HSCs showed the highest proliferation and expansion capacities in culture, and were found to be more closely related, in transcriptional terms, to MPCs than to EPCs. This correlated with the fact that after 30 days, only cultures initiated with HSCs and MPCs were sustained. Expression of cell cycle and cell division-related genes was enriched in EPCs. Such cells showed significantly higher proliferation than MPCs, however, their expansion potential was reduced, so that cultures initiated with EPCs declined after 15 days and became exhausted by day 30. Proliferation and expansion of HSCs and EPCs were higher in the presence of a cytokine combination that favors erythropoiesis, whereas the growth of MPCs was higher under a cytokine combination that favors myelopoiesis. CONCLUSION: This study shows a correlation between the transcriptional profiles of HSCs, MPCs, and EPCs, and their respective in vitro growth under particular culture conditions. These results may be relevant in the development of ex vivo systems for the expansion of hematopoietic cells for clinical application.


Assuntos
Citocinas , Células-Tronco Hematopoéticas , Antígenos CD34/metabolismo , Proliferação de Células , Células Cultivadas , Citocinas/genética , Sangue Fetal/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/fisiologia , Humanos , Transcriptoma
5.
Cell Transplant ; 31: 9636897221090257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35438589

RESUMO

Sepsis is associated with acute peritonitis, which can be induced by lipopolysaccharide exposure and feces. Generally, lipopolysaccharide induces mono-microbial peritonitis, whereas feces cause poly-microbial peritonitis; the latter is a more complicated and closer to the clinical diseases. Although several reports have discussed the mechanism of immune response in peritonitis-induced sepsis, however, the role of natural killer (NK) cells in sepsis, especially the relationship between NK cells and stabilization of the vascular endothelial barrier, is still unclear. Accordingly, in this study, we assessed the roles of NK cells in an acute sepsis model in mice. NK cells were injected via the tail vein into mice with acute sepsis, and nitric oxide (NO), anti-inflammatory cytokine, and angiogenic factors were tested to explore the effects of NK cells on sepsis. The survival rate of septic model mice infused with NK cells was significantly improved compared with the control group. Interestingly, the levels of NO, interleukin-10, and vascular endothelial growth factor (VEGF) decreased in NK cells therapy group. After the injection of NK cells, CD31 positive endothelial cells significantly increased in the kidneys and liver, although the expression of VEGF, ANGPT-1, and ET-1 was downregulated. Consistent with our hypothesis, the transfusion of NK cells into mice with sepsis blocked inflammation and increased endothelium integrity. Overall, these findings suggest that NK cells may block sepsis by modulating the VEGF pathway.


Assuntos
Peritonite , Sepse , Animais , Células Endoteliais , Endotélio , Fezes , Sangue Fetal , Células Matadoras Naturais , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Peritonite/induzido quimicamente , Peritonite/metabolismo , Sepse/terapia , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Environ Int ; 163: 107215, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35378444

RESUMO

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been shown to affect offspring behaviors in laboratory animals. Several epidemiological studies investigated associations between prenatal PFAS exposure and child neurodevelopment, but results were inconclusive. We examined associations between cord blood concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and cognitive development in children from 4 to 40 months of age. METHODS: This study included 598 mother-child pairs who participated in the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study), a prospective birth cohort study in Japan. PFOA and PFOS were quantified in cord blood. The Mullen Scales of Early Learning (MSEL) was used to assess child cognitive function at 4, 6, 10, 14, 18, 24, 32, and 40 months of age. For each of log 2-transformed PFOA and PFOS concentrations, we examined: 1) associations with the scores of MSEL Early Learning Composite (Composite) and four subscales (Fine Motor, Visual Reception, Receptive Language, Expressive Language) at each assessment time point; and 2) associations with longitudinal changes in the Composite and subscale scores. RESULTS: MSEL Composite scores were inversely associated with PFOA at 18 months of age (per 2-fold increase in concentration: ß = -2.23, 95% CI: -3.91, -0.56), but not at other ages. When accounting for changes in scores from 4 to 40 months of age, PFOA and PFOS were positively associated with Composite as well as Receptive and Expressive Language scores. Child's sex modified associations between PFOA and Composite scores at 14, 18, and 40 months and those between PFOS and Composite scores at 14 months, showing negative associations among females. CONCLUSIONS: In this study, cord blood PFOA and PFOS concentrations showed mixed associations with child cognitive functions at specific age but had positive associations with longitudinal changes in cognitive development from 4 to 40 months of age.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Efeitos Tardios da Exposição Pré-Natal , Caprilatos , Cognição , Estudos de Coortes , Feminino , Sangue Fetal , Humanos , Masculino , Mães , Gravidez , Estudos Prospectivos
7.
Bioengineered ; 13(4): 9564-9574, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35387551

RESUMO

Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) have been reported to possess cardioprotective effects in diseases. However, its effects on cardiomyopathy remain unclear. This study aimed to the therapeutic effects of UCBMSC transplantation on adriamycin (ADR)-induced cardiomyopathy. UCBMSCs isolated from human UCB were identified by detecting surface markers (CD29, CD90, CD34, and CD45) using flow cytometry. The effect of UCBMSCs on left ventricular end-diastolic dimension (LVEDD), left ventricular systolic end-diastolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fraction shortening (LVFS) were determined by echocardiography. Histological changes were observed by HE and Masson staining. The serum levels of collagen-I (Col-I), brain natriuretic peptide (BNP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured by corresponding kits. The protein levels of IL-6, IL-10, and TNF-α were measured by Western blotting. The isolated UCBMSCs manifested the positive expression of CD29 and CD90, and the negative expression of CD34 and CD45. UCBMSC transplantation significantly reduced LVEDD and LVESD, and increased LVEF and LVFS in ADR-induced cardiomyopathy model rats. Cardiac injury and high collagen deposition in model rats were alleviated by UCBMSC treatment. Moreover, UCBMSCs decreased the serum levels of Col-I, BNP, AST, LDH, CK, CK-MB, IL-6, IL-10, and TNF-α in model rats. Overall, UCBMSCs exert the therapeutic effects on ADR-induced cardiomyopathy through recovering the myocadiac function and alleviating the inflammatory response.


Assuntos
Cardiomiopatias , Células-Tronco Mesenquimais , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/terapia , Colágeno , Doxorrubicina/toxicidade , Sangue Fetal , Interleucina-10 , Interleucina-6 , Ratos , Volume Sistólico , Fator de Necrose Tumoral alfa , Função Ventricular Esquerda/fisiologia
8.
J Exp Med ; 219(5)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35416936

RESUMO

The paradox of fetomaternal tolerance has puzzled immunologists and reproductive biologists alike for almost 70 yr. Even the idea that the conceptus evokes a uniformly tolerogenic immune response in the mother is contradicted by the long-appreciated ability of pregnant women to mount robust antibody responses to paternal HLA molecules and RBC alloantigens such as Rh(D). Synthesizing these older observations with more recent work in mice, we discuss how the decision between tolerance or immunity to a given fetoplacental antigen appears to be a function of whether the antigen is trophoblast derived-and thus decorated with immunosuppressive glycans-or fetal blood cell derived.


Assuntos
Sangue Fetal , Trofoblastos , Animais , Feminino , Feto , Antígenos HLA , Humanos , Tolerância Imunológica , Isoantígenos , Camundongos , Gravidez
9.
BMC Genomics ; 23(1): 221, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305575

RESUMO

BACKGROUND: Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance. METHODS: We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data. RESULTS: We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts. CONCLUSIONS: Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants' methylome.


Assuntos
Metilação de DNA , Sangue Fetal , Canadá , Epigenoma , Feminino , Sangue Fetal/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Gravidez
10.
BMC Pregnancy Childbirth ; 22(1): 216, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35300620

RESUMO

BACKGROUND: To evaluate the impact of interval between induction of spinal anesthesia to delivery of the fetus by elective cesarean section on umbilical arterial pH and neonatal outcome. PATIENTS AND METHODS: Two hundred and twenty pregnant women who were planned for elective cesarean section at term under spinal anesthesia were recruited. Minimum systolic, diastolic and mean arterial blood pressures (SBP, DBP, MAP) and largest pressure decrease (SBP, DBP, MPA) were also recorded. Induction of spinal anesthesia to delivery interval was measured. Following delivery, umbilical arterial cord analysis for pH and base deficit were done. Apgar scores at 1 min and at 5 min, neonatal intensive care unit (NICU) admission, need for mechanical ventilation and incidence of hypoxemic-ischemic encephalopathy were recorded. RESULTS: Induction of spinal anesthesia to delivery interval was 25.7 ± 5.6 min. Lowest SBP and MAP reached during cesarean delivery were 88.9 ± 7.3 mmHg and 60.4 ± 5.6 mmHg, respectively. MAP < 65 mmHg was reached in 136 (62%) patients with a decrease of MAP of > 20% in 149 (68%) patients. Duration of the longest hypotension episode was 3.3 ± 2.2 min. All patients required ephedrine administration for hypotensive episodes with an average dosage of 11.4 ± 3.2 mg. Umbilical pH of 7.3 ± 0.1 and base deficit of 8.3 ± 4.4 mmol/l were recorded. Apgar scores at 5 min were 8.5 ± 1.2. Eight (3.6%) neonates were admitted in the NICU. One neonate needed mechanical ventilation. There were no cases of hypoxemic-ischemic encephalopathy. There were inverse correlations between induction of spinal anesthesia to delivery interval, body mass index (BMI) and duration of longest hypotension episode in relation to umbilical pH (r = -0.817, -0.395 and -0.268, respectively). Cut off value for induction of spinal anesthesia to delivery interval greater than 27 min predicted an umbilical pH of < 7.2. Cut off value for the duration of the longest hypotension episode greater than 5 min predicted an umbilical pH of < 7.2. Cut off value for BMI greater than 35 kg/m2 predicted an umbilical pH of < 7.2. CONCLUSION: Prolonged interval between induction of spinal anesthesia to delivery could be associated with neonatal acidosis. This could be aggravated by maternal obesity and prolonged duration of hypotension episodes during cesarean delivery.


Assuntos
Raquianestesia , Cesárea , Sangue Fetal/química , Cordão Umbilical/química , Acidose/epidemiologia , Índice de Apgar , Pressão Sanguínea , Feminino , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Gravidez , Fatores de Tempo
11.
BMC Neurol ; 22(1): 123, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351020

RESUMO

INTRODUCTION: The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. METHODS: Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. RESULTS: There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (ß: 7.10; 95%CI: 2.08, 12.76; Cohen's d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (ß: -0.58; 95%CI: -1.18, -0.11; Cohen's d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. CONCLUSIONS: This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).


Assuntos
Paralisia Cerebral , Adolescente , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Método Duplo-Cego , Feminino , Sangue Fetal , Humanos , Masculino , Qualidade de Vida
12.
J Cell Mol Med ; 26(8): 2404-2416, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35249258

RESUMO

Red blood cells (RBCs) generated ex vivo have the potential to be used for transfusion. Human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) possess unlimited self-renewal capacity and are the preferred cell sources to be used for ex vivo RBC generation. However, their applications are hindered by the facts that the expansion of ES/iPS-derived erythroid cells is limited and the enucleation of ES/iPS-derived erythroblasts is low compared to that derived from cord blood (CB) or peripheral blood (PB). To address this, we sought to investigate the underlying mechanisms by comparing the in vitro erythropoiesis profiles of CB CD34+ and ES CD34+ cells. We found that the limited expansion of ES CD34+ cell-derived erythroid cells was associated with defective cell cycle of erythroid progenitors. In exploring the cellular and molecular mechanisms for the impaired enucleation of ES CD34+ cell-derived orthochromatic erythroblasts (ES-ortho), we found the chromatin of ES-ortho was less condensed than that of CB CD34+ cell-derived orthochromatic erythroblasts (CB-ortho). At the molecular level, both RNA-seq and ATAC-seq analyses revealed that pathways involved in chromatin modification were down-regulated in ES-ortho. Additionally, the expression levels of molecules known to play important role in chromatin condensation or/and enucleation were significantly lower in ES-ortho compared to that in CB-ortho. Together, our findings have uncovered mechanisms for the limited expansion and impaired enucleation of ES CD34+ cell-derived erythroid cells and may help to improve ex vivo RBC production from stem cells.


Assuntos
Eritropoese , Sangue Fetal , Antígenos CD34/metabolismo , Diferenciação Celular , Cromatina/metabolismo , Células-Tronco Embrionárias/metabolismo , Células Eritroides , Humanos
14.
Artigo em Inglês | MEDLINE | ID: mdl-35328979

RESUMO

Particulate matter with a diameter of ≤10 µm (PM10) and nitrogen dioxide (NO2) affect the DNA methylation in the fetus, but epigenetic studies regarding prenatal exposure to air pollution in Asia are lacking. Therefore, this study aimed to assess whether there is any association between the ambient concentrations of PM10 and NO2 and CpG methylation in the cord blood DNA by using a Korean birth cohort. The concentrations of the air pollutants were incorporated into the final LUR model by using the maternal address data. The methylation level was determined using HumanMethylationEPIC BeadChip and a linear regression analysis model. A multipollutant model including both PM10 and NO2 and models with single pollutants were used for each trimester exposure. The number of differentially methylated positions was the largest for midpregnancy exposure in both the single pollutant models and the multipollutant regression analysis. Additionally, gene-set analysis regarding midpregnancy exposure revealed four gene ontology terms (cellular response to staurosporine, positive regulation of cytoskeleton organization, neurotransmitter transport, and execution phase of apoptosis). In conclusion, these findings show an association between prenatal PM10 and NO2 exposure and DNA methylation in several CpG sites in cord blood cells, especially for midpregnancy exposure.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Células Sanguíneas , Metilação de DNA , Feminino , Sangue Fetal/química , Humanos , Exposição Materna/estatística & dados numéricos , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética
15.
Biomed Res Int ; 2022: 6496773, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342750

RESUMO

Objective: To investigate synergic therapeutic effects of combined injection of intralesional mesenchymal stem cells derived from human umbilical cord blood (UCB-MSCs) and polydeoxyribonucleotide (PDRN) combined with microcurrent therapy (MIC) on full thickness rotator cuff tendon tear (FTRCTT) in rabbit models. Methods: Thirty-two rabbit models were assigned to 4 different groups. FTRCTT in the supraspinatus tendon was created. After 6 weeks, 4 types of procedures (0.2 mL normal saline injection, group 1 (G1-NS); 0.2 mL SC injection, group 2 (G2-MSC); 0.2 mL SC and weekly four injections of 0.2 mL PDRN with sham MIC, group 3 (G3-MSC+PDRN+sham MIC); and 0.2 mL SC and weekly four injections of 0.2 mL PDRN with MIC for four weeks, group 4 (G4-MSC+PDRN+MIC)) were performed in FTRCTT. Gross morphologic and histological changes of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (PECAM-1) and motion analysis were performed. Results: There was a significant difference in gross morphologic changes between baseline and week 4 posttreatment in group 4 compared to the other three groups (p = 0.01). In groups 3 and 4, all parameters of histochemical and motion analysis have been found to be significantly greater than the ones in groups 1 and 2 (p < 0.05). In group 4, PCNA-, VEGF-, and PECAM-1-stained cells, as well as walking distance, were significantly greater than the ones in group 3 (p < 0.05). Conclusion: The treatment with UCB-MSCs and PDRN combined with MIC might be the most effective in rabbit models' traumatic FRTCTT.


Assuntos
Células-Tronco Mesenquimais , Lesões do Manguito Rotador , Animais , Sangue Fetal , Humanos , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Polidesoxirribonucleotídeos/farmacologia , Antígeno Nuclear de Célula em Proliferação , Coelhos , Regeneração , Fator A de Crescimento do Endotélio Vascular
16.
BMC Pediatr ; 22(1): 111, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232426

RESUMO

OBJECTIVE: To evaluate the effect of later cord clamping (LCC) on umbilical arterial blood gas in neonates of diabetic mothers. METHODS: This prospective study included a group of 160 diabetic mothers (DM) whose neonates were randomized to immediate cord clamping (ICC) (≤ 15 s after birth) or LCC (≥ 30 s after birth), and a group of 208 non-diabetic mothers (NDM) whose neonates were randomized to ICC or LCC as a reference. Cord arterial pH, base excess (BE), bicarbonate (HCO3-), partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), lactate, hemoglobin, hematocrit and glucose were compared among groups. RESULTS: In neonates of DM, there was no significant difference in cord arterial pH between the ICC and LCC group. LCC of ≥ 30 s decreased umbilical arterial HCO3- and BE and increased lactate (ICC versus LCC, HCO3-: 24.3 (22.7, 25.8) versus 23.7 (22.3, 24.7) mmol/L, P = 0.01; BE: -2.70 (-4.80, -1.50) versus - 3.72 (-5.66, -2.36) mmol/L, P = 0.006; lactate: 2.1 (1.6, 3.7) versus 2.7 (2.1, 4.3) mmol/L, P = 0.005), without the alterations of pCO2, pO2, hemoglobin, hematocrit and glucose. Similar results were found in neonates of NDM (ICC versus LCC, HCO3-: 24.3 (23.1, 25.7) versus 23.5 (22.3, 24.8) mmol/L, P = 0.01; BE: -2.39 (-3.73, -1.51) versus - 3.40 (-4.73, -1.91) mmol/L, P = 0.001; lactate: 2.2 (1.9, 3.3) versus 2.5 (2.0, 4.3) mmol/L, P = 0.01), except for the higher level of hemoglobin in the LCC group. The majority of diabetic mothers (ICC: 92.0%; LCC: 91.8%) had good blood glucose control. No differences were observed in acid-base status and glucose between neonates of DM and neonates of NDM in both ICC and LCC, but hemoglobin and hematocrit were elevated after ICC in neonates of DM compared to neonates of NDM. CONCLUSIONS: Later cord clamping of ≥ 30 s resulted in a tendency towards metabolic acidosis of umbilical arterial blood in neonates of DM and NDM. Umbilical arterial blood gas parameters at birth were similar in neonates of DM and NDM. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04369313 ; date of registration: 30/04/2020 (retrospectively registered).


Assuntos
Diabetes Mellitus , Sangue Fetal , Constrição , Feminino , Sangue Fetal/metabolismo , Glucose/metabolismo , Hemoglobinas/metabolismo , Humanos , Recém-Nascido , Ácido Láctico/metabolismo , Mães , Estudos Prospectivos , Cordão Umbilical
17.
PLoS One ; 17(3): e0265186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35271679

RESUMO

OBJECTIVE: An increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF). METHODS: In this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay. RESULTS: In 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01). CONCLUSION: Our study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.


Assuntos
Líquido Amniótico , Fator Neurotrófico Derivado do Encéfalo , Índice de Massa Corporal , Estudos Transversais , Feminino , Sangue Fetal , Humanos , Limite de Detecção , Mães , Placenta , Gravidez , Estudos Prospectivos
18.
Stem Cell Res ; 61: 102752, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35313264

RESUMO

Hematopoietic stem and progenitor cells (HSPC) from umbilical cord blood (UCB) are used for transplantation to treat blood disorders. Methods to estimate the HSPC count in umbilical cord blood, and thereby identify high-value blood units, are time-consuming and costly. Recent studies indicate that the UCB plasma protein composition relates to the HSPC count. We compared the plasma proteome of UCB with high vs low HSPC cell count (>115 × 106 vs < 51 × 106 CD34+ cells l-1) by using a combination of global untargeted MS quantitative proteomics and targeted proximity extension assay (PEA) proteomics. For the MS platform, 96 proteins differed significantly between the CD34+ groups, and out of these, 44 proteins showed more than a two-fold difference. Seven pathways were enriched in high CD34+ samples, including pathways relating to platelets, coagulation, and lipid transport. For the PEA platform, 61 proteins were differentially abundant, and among these 7 proteins showed more than a two-fold difference between groups. In the PEA data, a high CD34+ cell count was associated with a protein hub with functions in platelet degranulation. We conclude that the HSPC count is related to the UCB plasma proteome, but that further studies are needed to discern if these findings reflect causal relationships.


Assuntos
Sangue Fetal , Transplante de Células-Tronco Hematopoéticas , Antígenos CD34/metabolismo , Moléculas de Adesão Celular/metabolismo , Contagem de Células , Sangue Fetal/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Plasma/metabolismo , Proteoma/metabolismo
19.
Transfusion ; 62(4): 871-886, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35322408

RESUMO

BACKGROUND: Following delivery, blood tests are performed on umbilical cord blood (CB) to avoid neonatal venipuncture. Despite widespread and longstanding CB testing, no guidelines exist to suggest which immunohematology tests should be performed on CB. STUDY DESIGN AND METHODS: We performed a scoping review, surveyed national practice, and developed guidance statements concerning CB testing. Database searches identified relevant articles. A survey was sent to all Canadian hospitals and transfusion laboratories that perform perinatal testing. A national panel of experts was convened to develop guidance statements. RESULTS: A total of 116 articles met the inclusion criteria and were summarized. Literature on CB testing is limited; few studies have investigated laboratory testing methodologies or validated CB test results with peripheral samples. The survey was completed by 580/597 institutions (97%); 85% were community hospitals and 16% had a neonatal intensive care unit. There is diversity in the types of CB tests performed and variability in practice. While most centers order appropriately, some laboratories routinely perform CB tests that are not clinically indicated (e.g., direct antiglobulin testing for all neonates) and other do not perform CB tests when results would be beneficial (e.g., phenotype on CB when mother has a clinically significant antibody). Fifteen guidance statements were developed. DISCUSSION: This study highlights variability in CB testing, likely reflecting evidence gaps, methodology differences between studies, and lack of guidelines. CB tests should only be performed when indicated and validated on this sample type. The presented guidance statements aim to standardize practice and encourage judicious CB sampling.


Assuntos
Transfusão de Sangue , Sangue Fetal , Canadá , Feminino , Humanos , Gravidez , Inquéritos e Questionários
20.
Int J Mol Sci ; 23(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35269664

RESUMO

Chronic kidney disease (CKD) is characterized by structural abnormalities and the progressive loss of kidney function. Extracellular vesicles (EVs) from human umbilical cord tissue (hUCT)-derived mesenchymal stem cells (MSCs) and expanded human umbilical cord blood (hUCB)-derived CD133+ cells (eCD133+) maintain the characteristics of the parent cells, providing a new form of cell-free treatment. We evaluated the effects of EVs from hUCT-derived MSCs and hUCB-derived CD133+ cells on rats with CDK induced by an adenine-enriched diet. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and electron microscopy. The animals were randomized and divided into the MSC-EV group, eEPC-EV group and control group. Infusions occurred on the seventh and 14th days after CKD induction. Evaluations of kidney function were carried out by biochemical and histological analyses. Intense labeling of the α-SMA protein was observed when comparing the control with MSC-EVs. In both groups treated with EVs, a significant increase in serum albumin was observed, and the increase in cystatin C was inhibited. The results indicated improvements in renal function in CKD, demonstrating the therapeutic potential of EVs derived from MSCs and eCD133+ cells and suggesting the possibility that in the future, more than one type of EV will be used concurrently.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Insuficiência Renal Crônica , Animais , Células Cultivadas , Vesículas Extracelulares/metabolismo , Sangue Fetal , Células-Tronco Mesenquimais/metabolismo , Ratos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia
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