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Metabolomics comparison of cord and peripheral blood-derived serum eye drops for the treatment of dry eye disease.
Quartieri, E, Marraccini, C, Merolle, L, Pulcini, S, Buzzi, M, Guardi, M, Schiroli, D, Baricchi, R, Pertinhez, TA
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2021;(4):103155
Abstract
Allogeneic peripheral blood-derived (PBS) serum eye drops have been largely used in the treatment of dry eye disease (DED). Recently, cord blood has emerged as an effective alternative serum source (cord blood serum, CBS), containing a higher amount of growth factors than PBS, it holds the promise of a better capability to stimulate corneal healing. However, the lack of a standardized method for preparation, dispensation, storage and a poor biochemical characterization still hamper the establishment of a clinical consensus. Here the metabolomes of the two different serum eye drop preparations were compared using proton nuclear magnetic resonance spectroscopy. We found that both PBS and CBS contained several organic compounds, the majority of them already detected in human tears and may be thereby considered lacrimal substitutes. Metabolites having in the multivariate statistical analysis Partial least squares discriminant analysis (PLS-DA) a VIP scores > 1.0 were considered to be significantly different. All the metabolites identified were found to have a p < 0.05 in the univariate analysis. CBS, in particular, showed the highest amount of choline, myo-inositol, glutamine, creatine and β-hydroxybutyrate. These evidences constitute relevant advances towards serum eye drops characterization and confirm that cord blood is a valid alternative source of serum eye drops.
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Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial.
Taesuwan, S, McDougall, MQ, Malysheva, OV, Bender, E, Nevins, JEH, Devapatla, S, Vidavalur, R, Caudill, MA, Klatt, KC
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021;(12):e22063
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Abstract
Pregnancy places a unique stress upon choline metabolism, requiring adaptations to support both maternal and fetal requirements. The impact of pregnancy and prenatal choline supplementation on choline and its metabolome in free-living, healthy adults is relatively uncharacterized. This study investigated the effect of prenatal choline supplementation on maternal and fetal biomarkers of choline metabolism among free-living pregnant persons consuming self-selected diets. Participants were randomized to supplemental choline (as choline chloride) intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d methyl-d9-choline; intervention) or 25 mg/d d9-choline (control) from gestational week (GW) 12-16 until Delivery. Fasting blood and 24-h urine samples were obtained at study Visit 1 (GW 12-16), Visit 2 (GW 20-24), and Visit 3 (GW 28-32). At Delivery, maternal and cord blood and placental tissue samples were collected. Participants randomized to 550 (vs. 25) mg supplemental choline/d achieved higher (p < .05) plasma concentrations of free choline, betaine, dimethylglycine, phosphatidylcholine (PC), and sphingomyelin at one or more study timepoint. Betaine was most responsive to prenatal choline supplementation with increases (p ≤ .001) in maternal plasma observed at Visit 2-Delivery (relative to Visit 1 and control), as well as in the placenta and cord plasma. Notably, greater plasma enrichments of d3-PC and LDL-C were observed in the intervention (vs. control) group, indicating enhanced PC synthesis through the de novo phosphatidylethanolamine N-methyltransferase pathway and lipid export. Overall, these data show that prenatal choline supplementation profoundly alters the choline metabolome, supporting pregnancy-related metabolic adaptations and revealing biomarkers for use in nutritional assessment and monitoring during pregnancy.
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Zinc Content in Cord Blood Is Associated with Maternal Age and Parity.
Youssof, AL, Kassim, NL, Rashid, SA, De Ley, M, Rahman, MT
Biological trace element research. 2017;(1):17-26
Abstract
At childbirth (parturition), zinc (Zn) homeostasis in cord blood (CB) can be affected by a number of factors: Zn in maternal blood, parturition related stress as well as metallothionein (MT). Both Zn and stress are known inducers of MT which is primarily involved in Zn homeostasis. This study analyzed Zn concentration [Zn], in CB components and MT-2A transcription in CB mononuclear cells (MNC) in relation to primiparous and multiparous childbirth. [Zn] in CB (n = 47) plasma, erythrocytes, and MNCs were measured by atomic absorption spectrophotometry (λ = 213.9 nm). The MT-2A transcription in CB-MNC was quantified using real-time PCR. Significant correlations (Pearson r) were found between: plasma-[Zn] and erythrocyte-[Zn] (p = 0.002); [Zn] and MT-2A messenger RNA (mRNA) (p = 0.000) in CB-MNC. Student's t tests showed higher levels of MT-2A mRNA and MNC-[Zn] in CB of older (≥25 years) compared to younger mothers (≤24 years) (p = 0.043 and p = 0.016, respectively). Significantly higher [Zn] was found in CB plasma (p = 0.017) and MNC (p = 0.041) of older primiparous compared to the younger primiparous and older multiparous mothers respectively. MT-2A mRNA in CB-MNC was significantly lower in CB of younger primiparous mothers compared to their older counterparts (p = 0.001). Path analysis showed that MNC-[Zn] (β = 0.83; p = 0.000) had a greater influence on MT-2A mRNA expression, compared to parity (β = -0.14; p = 0.033). Higher [Zn] in CB of primiparous mothers could be linked to higher stress during parturition, however, might be beneficial for the growth and development of the child. Together MNC-[Zn] and parity contributed ~70 % of the MT-2A transcription in CB-MNC.
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Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.
Shah, N, Li, L, McCarty, J, Kaur, I, Yvon, E, Shaim, H, Muftuoglu, M, Liu, E, Orlowski, RZ, Cooper, L, et al
British journal of haematology. 2017;(3):457-466
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Abstract
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m2 on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 106 , 1 × 107 , 5 × 107 and 1 × 108 CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D+ /NKp30+ ). These data warrant further development of this novel cellular therapy.
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Supplementation of docosahexaenoic acid (DHA) / Eicosapentaenoic acid (EPA) in a ratio of 1/1.3 during the last trimester of pregnancy results in EPA accumulation in cord blood.
Büyükuslu, N, Ovalı, S, Altuntaş, ŞL, Batırel, S, Yiğit, P, Garipağaoğlu, M
Prostaglandins, leukotrienes, and essential fatty acids. 2017;:32-36
Abstract
Omega-3 fatty acids (n-3 FA), specifically DHA, are associated with fetal growth and development. We aimed to determine the levels of DHA and EPA in cord serum after n-3 FA supplementation during the last trimester of pregnancy. Among 55 women, 23 were administered daily one capsule of n-3 FA supplement, involving DHA/EPA in a ratio of 1/1.3. Twenty nine women were enrolled as control group. Blood samples were collected at 22-24 weeks of gestation and at delivery. Fatty acids were analyzed with the method of GC-MS. Cord DHA level increased and EPA level decreased in both groups between the days of 22-24 and delivery. However, decrease in cord EPA level was significant in control group (p < 0.001) but not in supplement group (p > 0.05). Supplementation of DHA/EPA in a ratio of 1/1.3 during the last trimester of pregnancy caused higher cord EPA level compared to control group indicating an accumulation in umbilical cord.
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Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status.
Jones, AD, Zhao, G, Jiang, YP, Zhou, M, Xu, G, Kaciroti, N, Zhang, Z, Lozoff, B
European journal of clinical nutrition. 2016;(8):918-24
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Abstract
BACKGROUND/OBJECTIVES Obesity among pregnant women may adversely affect both maternal iron status throughout pregnancy and placental transfer of iron. The objective of this study was to determine the association of maternal body mass index (BMI) with (1) maternal iron status and inflammation in mid and late pregnancy, (2) the change in maternal iron status throughout pregnancy and (3) neonatal iron status. SUBJECTS/METHODS We examined longitudinal data from 1613 participants in a pregnancy iron supplementation trial in rural China. Women with uncomplicated singleton pregnancies were enrolled in the early second trimester of pregnancy and followed through parturition. Maternal blood samples obtained at enrollment and in the third trimester and cord blood samples were analyzed for a range of hematological and iron biomarkers. RESULTS There was a negative association between maternal BMI and iron status at enrollment (transferrin receptor (sTfR): r=0.20, P<0.001; body iron (BI): r=-0.05; P=0.03). This association was markedly stronger among obese women. Maternal BMI was positively associated with maternal inflammation (C-reactive protein: r=0.33, P<0.001). In multiple linear regression models, maternal BMI was negatively associated with neonatal iron status (cord serum ferritin: -0.01, P=0.008; BI: -0.06, P=0.006) and associated with a lower decrease in iron status throughout pregnancy (sTfR: -4.6, P<0.001; BI: 1.1, P=0.004). CONCLUSIONS Maternal obesity during pregnancy may adversely affect both maternal and neonatal iron status, potentially through inflammatory pathways.
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The presence of B-cell activating factor (BAFF) in umbilical cord blood in both healthy and pre-eclamptic pregnancies and in human breast milk.
Bienertova-Vasku, J, Zlamal, F, Tomandl, J, Hodicka, Z, Novak, J, Splichal, Z, Ventruba, P, Thon, V, Vasku, A
Journal of reproductive immunology. 2015;:89-93
Abstract
B-cell activating factor (BAFF) is an important immune regulator that was recently reported to be secreted by placenta. The aim of the study was to investigate the presence of BAFF in umbilical cord blood, maternal serum, and breast milk in normal and in pre-eclamptic pregnancies. Pairs of maternal serum/umbilical cord blood were obtained from 12 pre-eclamptic and 34 physiological pregnancies. Another cohort of 10 healthy lactating women was established that was followed up for 6 months following delivery to investigate BAFF levels in breast milk. BAFF levels in maternal peripheral blood were significantly higher in physiological pregnancies than in pre-eclamptic pregnancies (p < 0.03). Furthermore, we observed a consistent presence of BAFF in breast milk during the 6-month post-partum period of breastfeeding. In this study, we demonstrate that BAFF levels are significantly lower in maternal peripheral blood in pre-eclamptic pregnancies. We also report the consistent presence of BAFF in breast milk in healthy women. More research into the role of BAFF in pregnancy, and during breastfeeding, is imperative.
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New evaluation of fetal oxidative stress: measurement of the umbilical cord blood dimethyl sulfate-induced ascorbyl-free radical by an electron spin resonance method.
Nishida, Y, Matsumoto, S, Noguchi, T, Narahara, H
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2014;(15):1550-4
Abstract
OBJECTIVE The aim is to evaluate intrapartum fetal oxidative stress in real-time by umbilical cord blood dimethyl sulfate (DMSO)-induced ascorbyl-free radical (AFR) measured by an electron spin resonance (ESR) method. METHODS Seventy-five mothers delivering at gestational age after 37 weeks were recruited. They were divided into three groups: spontaneous vaginal birth (n = 27), elective cesarean section (CS) (n = 34), and emergency CS due to non-reassuring fetal status (n = 14). Umbilical artery (UA) and venous (UV) cord blood gas analysis was performed. Serum levels of DMSO-induced AFR (AFR/DMSO) that reflect vitamin C concentrations were measured by ESR spectroscopy. RESULTS Blood gas analysis showed no significant differences among the groups. UA-AFR/DMSO level of elective CS group was significantly lower compared with spontaneous delivery group (0.32 ± 0.12 versus 0.46 ± 0.14, p < 0.005). Emergency CS group showed significantly lower levels of UA-AFR/DMSO compared with elective CS group (0.25 ± 0.11 versus 0.32 ± 0.12, p < 0.005). UV-AFR/DMSO levels had no significant difference among the groups. CONCLUSIONS It is suggested that fetal cord blood AFR/DMSO is a sensitive marker to assess fetal oxidative stress during delivery.
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Effects of ethnicity and vitamin D supplementation on vitamin D status and changes in bone mineral content in infants.
Abrams, SA, Hawthorne, KM, Rogers, SP, Hicks, PD, Carpenter, TO
BMC pediatrics. 2012;:6
Abstract
BACKGROUND To evaluate the effects on serum 25(OH)D and bone mineralization of supplementation of breast-fed Hispanic and non-Hispanic Caucasian infants with vitamin D in infants in Houston, Texas. METHODS We measured cord serum 25(OH)D levels, bone mineral content (BMC), bone mineral density (BMD) and their changes over 3 months of life with 400 IU/day of vitamin D3 supplementation. RESULTS Cord serum 25(OH)D was significantly lower in Hispanic than non-Hispanic Caucasian infants (16.4 ± 6.5 ng/mL, n = 27, vs 22.3 ± 9.4 n = 22, p = 0.013). Among 38 infants who completed a 3 month vitamin D supplementation intervention, provision of 400 IU/day of vitamin D increased final 25(OH)D to a higher level in non-Hispanic Caucasian compared to Hispanic infants. There was no significant relationship between cord serum 25(OH)D and BMC or BMD in the first week of life (n = 49) or after 3 months of vitamin D supplementation. CONCLUSION Low cord 25(OH)D levels are seen in Hispanic infants, but their functional significance is uncertain related to bone health in a southern US setting. Daily vitamin D intake of 400 IU during the first months of life appears adequate to increase serum 25(OH)D and support BMC increases despite low initial 25(OH)D levels in some infants. TRIAL REGISTRATION ClincalTrials.gov NCT00697294.
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Biochemical tissue-specific injury markers of the heart and brain in postpartum cord blood.
Kocylowski, RD, Dubiel, M, Gudmundsson, S, Sieg, I, Fritzer, E, Alkasi, O, Breborowicz, GH, von Kaisenberg, CS
American journal of obstetrics and gynecology. 2009;(3):273.e1-273.e25
Abstract
OBJECTIVE We sought to establish references ranges and to test the hypothesis that biochemical tissue-specific markers for the heart in umbilical cord blood of newborns with cardiac defects and intrauterine growth restriction (IUGR) are abnormal. STUDY DESIGN A prospective study was conducted. Serum samples of the umbilical vein (n = 280) and artery (n = 156) from 599 healthy newborns at 37(+0)-42(+0) weeks of gestation were collected. Total creatine kinase (CK), CK-MB heart type (CK-MB), cardiac troponin T (cTnT), myoglobin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and S100 were measured. Reference ranges for each marker were constructed. Concentrations of tissue-specific markers from umbilical cord blood of neonates with cardiac defects (n = 10) and IUGR (n = 41) were plotted against the established reference ranges. RESULTS Reference ranges for each studied marker were established for both umbilical artery and vein. In fetuses with cardiac defects, both NT-proBNP (4/6 [66%] in the artery, 7/10 [70%] in the vein) and cTnT (2/10 [20%] in the vein) were increased. In fetuses with IUGR in the vein, NT-proBNP (10/41 [24%]) and cTnT (5/41 [12%]) were increased, whereas S100 (9/41 [21%]) was decreased. CONCLUSION In a subset of neonates with cardiac defects or growth restriction, irrespective of the pH at birth, tissue-specific injury markers for the heart in umbilical cord blood are abnormal.