Cord Blood Research Articles

The Relationship between the Improvement Level in Blood Gas Parameters in Time and Brain MRI Findings in Newborns with the Diagnosis of Hypoxic Ischemic Encephalopathy.

In this study, we aimed to evaluate the relationship between the level of improvement in blood gas parameters in the first hours of age and normal and diffusion-restriction brain magnetic resonance imaging (MRI). The study is a retrospective cohort study. Cases of the diagnosis of hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia in our unit between January 2022 and January 2024 were included in the study. Clinical findings, blood gas values (first, cord; second, first hours of age; third, 24th hour of age), and MRI results were recorded from the case files and compared between normal and diffusion-restricted brain MRI groups. Diffusion-restricted brain MRI was detected in 10 out of a total of 19 cases. The 5-minute Apgar score was lower (p=0.038) and mechanical ventilator support was higher (P=.003) in the diffusion-restricted MRI group than in the normal MRI group. The relationship was shown between high base excess (P=.022) in cord blood gas, low HCO₃ (p=0.025) in the 24th hour blood gas, and convulsion (P=.033) in the diffusion-restricted MRI group. Additionally, it was found that only the improvement level of the pH value in the first hour of age was significant (P=.025) in the diffusion-restricted brain MRI group than in the normal MRI group. We showed that there was a relationship between diffusion-restricted brain MRI and the improvement level in the pH value in the first hours of age of patients diagnosed with HIE who received treatment for therapeutic hypothermia.

Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.

This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features. We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight. QEEG features included statistical moments, spectral power, and recurrence quantification analysis (RQA) features. We trained and evaluated Neo-GB on a University of California, San Francisco (UCSF) neonatal HIE dataset, augmenting training with publicly available neonatal electroencephalogram (EEG) datasets from Cork University and Helsinki University Hospitals. We assessed the performance of Neo-GB at providing dynamic and static forecasts with diagnostic performance metrics and incident/dynamic area under the receiver operating characteristic curve (iAUC) analyses. Model explanations were performed to assess contributions of QEEG features and channels to model predictions. The UCSF dataset included 60 neonates with HIE (30 with seizures). In subject-level static forecasting at 30 min after EEG initiation, baseline Neo-GB without time-dependent features had an area under the receiver operating characteristic curve (AUROC) of .76 and Neo-GB with time-dependent features had an AUROC of .89. In time-dependent evaluation of the initial seizure onset within a 24-h seizure occurrence period, dynamic forecast with Neo-GB demonstrated median iAUC = .79 (interquartile range [IQR] .75-.82) and concordance index (C-index) = .82, whereas baseline static forecast at 30 min demonstrated median iAUC = .75 (IQR .72-.76) and C-index = .69. Model explanation analysis revealed that spectral power, PMA, RQA, and cord blood gas values made the strongest contributions in driving Neo-GB predictions. Within the most influential EEG channels, as the preictal period advanced toward eventual seizure, there was an upward trend in broadband spectral power. This study demonstrates an ML model that combines QEEG with clinical features to forecast time-dependent risk of initial seizure onset in neonatal HIE. Spectral power evolution is an early EEG marker of seizure risk in neonatal HIE.

Studies of Lipid Profiles Among Infants with Respiratory Distress Syndrome

Background: Respiratory distress syndrome (RDS) is known as hyaline membrane disease (HMD). It is the major cause of neonatal respiratory distress, especially in preterm infants Infants with RDS present with tachapnea, cyanosis, grunting, subcostal and intercostal retractions and nasal flaring. Oliguria with mild generalized edema may be present. Oxygen requirement may increase rapidly and is typically higher than that seen in infant with transient tachapnea of the newborn (TTN). Objective: to evaluate the relationship between the maternal and cord blood lipid profiles in preterm babies with respiratory distress syndrome. Methods: This is a case control study which was conducted on 50 preterm neonates admitted to the neonatal intensive care unit of Shebin El-Kom teaching hospital between January 2020 and October 2021. Results: the mean of total cholesterol was significantly higher in infants whose mothers had received antenatal steroid for lung maturity than those whose mothers had not (P<0.05). But there was no significant difference in the mean of levels of TG, HDL-cholesterol, LDL-cholesterol and VLDL cholesterol between both groups. Also, There is a positive correlation between weight gain during pregnancy and neonatal cord blood levels of (Total cholesterol, TG, HDL-C, LDL-C and VLDL-C), There is a positive correlation between maternal blood levels of (total cholesterol, TG, LDL-C and VLDL-C) and their neonatal cord blood levels of (total cholesterol, TG, HDL-C, LDL-C and VLDL-C), There is a positive correlation between the maternal blood level of HDL-C and their neonatal cord blood levels of (total cholesterol and HDL-C).also, the cutoff values of cord blood (total Cholesterol, HDL-C, and LDL-C) below which RDS can be predicted are 80, 45.5 and 23.2 mg/dl respectively with a sensitivity of 83.3%, 86.7% and86.7% and with specificity of 95%, 80% and 70% respectively. Conclusion: RDS is accompanied with lipid alteration in the infants and their mothers. The results of this study point to the importance of measuring maternal serum and cord blood lipid profile as a predictor for the occurrence of RDS.

Maternal and Cord Blood Levels of Metals and Fetal Liver Function

Exposure to metals during pregnancy has been associated with adverse birth outcomes, but its impact on fetal liver function remains poorly understood. This study for the first time aimed to investigate the association between maternal and umbilical cord blood Metals levels and umbilical liver enzymes. A comprehensive analysis was conducted on 450 mother-newborn pairs in 2022, measuring 13 Metals in serum samples from pregnant women during the third trimester and umbilical cord blood samples. Regression analyses were utilized to examine the relationship between levels of maternal and umbilical cord blood Metals and the levels of gamma-glutamyl transferase (GGT), umbilical alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). G-comp analyses evaluated the combined effect of metals exposure on umbilical liver enzymes. Elevated levels of certain Metals in cord blood and maternal samples were positively linked with increased umbilical GGT, ALP, ALT, and AST levels. Notably, zinc (Zn) levels in cord blood exhibited an inverse correlation with umbilical liver enzyme levels. Furthermore, g-comp analyses revealed significant positive associations between exposure to metals mixtures and umbilical liver enzyme levels. An increase of one quartile in the mixture of maternal and umbilical Metals was linked with 99.45 U/L (95% CI:37.72, 161.19, p < 0.01), 2.79 (95% CI: 0.92, 4.65, p < 0.01), and 87.17 (95% CI: 53.96, 120.38, p < 0.01) increase in ALP, ALT and GGT levels. Further examination of the weight of Metals revealed As, Cd, Ni, Pb, Hg and Cr with the highest positive effects and Zn with the highest negative effect in the mixture effect on the umbilical liver enzyme. In summary, our results underscore the potential influence of prenatal heavy metal exposure on fetal liver function.

Omidubicel for Hematopoietic Cell Transplants: Considerations for Patients and Treatment Outcomes.

For patients with hematologic malignancies requiring allogeneic stem cell transplantation, alternative donor sources are needed when lacking access to a matched related or unrelated donor. Umbilical cord blood (UCB) has been an important alternative allograft donor source for these patients; however, several limitations exist. Omidubicel is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from UCB. Omidubicel was approved in May 2023 by the United States Food and Drug Administration based on the results of a Phase III trial comparing it to UCB transplantation in patients with high-risk hematologic malignancies. Median time to neutrophil engraftment was faster with omidubicel compared to UCB transplantation (12 days vs 22 days; p<0.001). There was also a lower incidence of grade 2/3 bacterial or invasive fungal infections with omidubicel compared to UCB transplantation (37% vs 57%; p=0.027). From a safety perspective, omidubicel has a boxed warning due to the risk of life-threatening infusion reactions, graft-versus-host disease, graft failure, and engraftment syndrome. Omidubicel represents an important advancement in developing novel alternative allograft donor sources. This also has important implications in ensuring access to alternative donor sources for ethnic and minority populations.

Using Lipid Parameters in Predicting Preterm Infants with Respiratory Distress Syndrome

Background: Respiratory distress syndrome is a clinical diagnosis which is warranted in a preterm newborn with respiratory difficulty, including tachypnea (&gt;60 breaths/min), chest retractions, and cyanosis in room air that persist or progress over the first 48-96 hr of life, and a characteristic chest radiographic appearance. Objective: to assess the cord blood lipid profile for predicting of preterm infants with respiratory distress syndrome. Methods: This is a case control study which was conducted on 50 preterm neonates admitted to the neonatal intensive care unit of Shebin El-Kom teaching hospital between January 2011 and October 2011. Results: the mean of weight gain during pregnancy in mothers of preterm with RDS was lower than the control group and the difference was statistically highly significant (P&lt;0.01). Also, there was significant difference (P&lt;0.05) regarding mode of delivery and antenatal steroid, however; no statistical significant difference was detected regarding maternal age, maternal weight, maternal BMI, pre-gravid height, the ruptured membrane &gt; 24 hr and parity between both groups. the mean of total cholesterol, HDL-cholesterol and LDL-cholesterol in the cord blood was lower in group A than in group B and the difference was statistically highly significant (P &lt;0.01), but there was no significant difference regarding the mean of both triglycerides and VLDL-cholesterol in both groups (P&gt;0.05).the mean of total cholesterol, HDL-cholesterol and LDL-cholesterol was lower in mothers of preterm infants with RDS than in control group and the difference was statistically highly significant (P &lt;0.01), but there was no significant difference was detected regarding the mean of levels triglycerides and VLDL-cholesterol in both groups (P &gt;0.05).the cutoff values of cord blood (total Cholesterol, HDL-C, and LDL-C) below which RDS can be predicted are 80, 45.5 and 23.2 mg/dl respectively with a sensitivity of 83.3%, 86.7% and 86.7% and with specificity of 95%, 80% and 70% respectively. Conclusion: We conclude that RDS is accompanied with lipid alteration in the infants and their mothers. The results of this study point to the importance of measuring of maternal serum and cord blood lipid profile as a predictor for the occurrence of RDS.

CAR-NK cells derived from cord blood originate mainly from CD56-CD7+CD34-HLA-DR-Lin- NK progenitor cells

Cord blood (CB)–derived chimeric antigen receptor (CAR)–natural killer (NK) cells targeting CD19 have been shown to be effective against B-cell malignancies. While human CD56+ NK cells can be expanded in vitro, NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB. Here we determined that CAR-NK cells were predominantly derived from CD56- NK progenitor cells. We first found that substantial numbers of CD19 CAR-NK cells were produced from CD56- CB mononuclear cells after in vitro culture for 2 weeks. Single-cell RNA sequencing analysis of CD56-CD3-CD14-CD19- CB mononuclear cells revealed that these cells could be subdivided into three subpopulations based on the expression of CD34 and HLA-DR. NK cells originated primarily from CD34-HLA-DR- cells. In addition, among the CD34-HLA-DR- cells, only CD7+ cells could differentiate into NK cells. These results indicate that CD56-CD7+CD34- HLA-DR- lineage marker (Lin)- cells are the major origin of human CB-derived CAR-NK cells, indicating the importance of developing methods to enhance the quality and quantity of NK cells produced from these NK progenitor cells.

Analysis of the relationship between neonatal birth weight and meconium metabolites based on birth cohort metabolomics

Neonatal birth weight is a crucial indicator of intrauterine growth and development with important implications for child development and adult health. The birth weight of a newborn is closely linked to the nutrition and health of the mother during pregnancy as well as genetic factors. Therefore, assessing the metabolic status of the fetus in utero is greatly significant for understanding the mechanisms responsible for abnormal birth weight. While previous studies often analyzed the impact of maternal metabolism on fetal development using umbilical cord blood from pregnant women, such blood may not accurately reflect the actual intrauterine environment owing to the barrier function of the placenta; moreover, obtaining biological samples during the fetal period is challenging. Meconium, the first feces excreted by a newborn, provides ideal biological material for studying maternal and infant health. Metabolomics can reveal metabolic changes in living organisms by analyzing small molecules in biological samples; hence studying meconium samples using metabolomics technology is expected to reveal fetal metabolic changes during pregnancy, thereby providing new insights into fetal nutritional intake, growth, and development, as well as metabolic pathways related to birth weight. To gain a deeper understanding of the metabolic changes associated with birth weight, this study collected metabolomic data from the meconium of 484 newborns in the established Xiaogan birth cohort using an untargeted metabolomics technique based on liquid chromatography-high resolution mass spectrometry (LC-HRMS) and analyzed the association between meconium metabolites and birth weight. This cohort exhibited incidence rates of low birth weight (<2500 g) and macrosomia (>4000 g) of 3.3% and 7.2%, respectively, which were roughly equivalent to the national average. Orthogonal partial least squares discriminant analysis revealed significant differences between the meconium metabolomes of the low birth weight and macrosomic groups when compared to the normal weight group. We discovered significant distinctions between the differential metabolites of newborns of low birth weight and those of normal weight, as well as between macrosomic and normal weight newborns that point to disparate biological pathways. Newborns with low birth weight exhibited significantly lower levels of critical amino acids, such as glutamate and proline, compared to the normal weight group, which may be associated with placental dysfunction and maternal nutritional deficiencies. Conversely, the meconium of macrosomic newborns contained significantly elevated levels of hormone metabolites such as estrone that reflected the pathophysiological state associated with maternal metabolic diseases or excessive placental hormone levels. Our study suggests that the metabolomic profile of the meconium reflects the metabolic pathways and regulatory mechanisms at play during fetal growth and development, and offers potential metabolic biomarkers and directions for future in-depth research into diseases related to fetal development. However, this study was based solely on the Xiaogan birth cohort, which was limited to specific regions and populations. A multicenter, multiethnic, and multiregional study is expected to help validate the universality of our research findings.

Orthobiologic Products: Preservation Options for Orthopedic Research and Clinical Applications.

The biological products used in orthopedics include musculoskeletal allografts-such as bones, tendons, ligaments, and cartilage-as well as biological therapies. Musculoskeletal allografts support the body's healing process by utilizing preserved and sterilized donor tissue. These allografts are becoming increasingly common in surgical practice, allowing patients to avoid more invasive procedures and the risks associated with donor site morbidity. Bone grafting is one of the most frequently used procedures in orthopedics and traumatology. Biologic approaches aim to improve clinical outcomes by enhancing the body's natural healing capacity and reducing inflammation. They serve as an alternative to surgical interventions. While preliminary results from animal studies and small-scale clinical trials have been promising, the field of biologics still lacks robust clinical evidence supporting their efficacy. Biological therapies include PRP (platelet-rich plasma), mesenchymal stem cells (MSCs)/stromal cells/progenitor cells, bone marrow stem/stromal cells (BMSCs), adipose stem/stromal cells/progenitor cells (ASCs), cord blood (CB), and extracellular vesicles (EVs), including exosomes. The proper preservation and storage of these cellular therapies are essential for future use. Preservation techniques include cryopreservation, vitrification, lyophilization, and the use of cryoprotective agents (CPAs). The most commonly used CPA is DMSO (dimethyl sulfoxide). The highest success rates and post-thaw viability have been achieved by preserving PRP with a rate-controlled freezer using 6% DMSO and storing other cellular treatments using a rate-controlled freezer with 5% or 10% DMSO as the CPA. Extracellular vesicles (EVs) have shown the best results when lyophilized with 50 mM or 4% trehalose to prevent aggregation and stored at room temperature.

Development of an enzyme-linked immunosorbent assay for newborns dried blood spot thyroglobulin.

Thyroglobulin (Tg) is a biomarker of iodine status. Newborn Tg is a more sensitive marker than neonatal TSH in detecting variations in iodine intake. This study aims to validate a Tg enzyme-linked immunosorbent assay (ELISA) for Tg determination on dried blood spots (DBS) in newborns. This study also set out to assess the stability of Tg and the influence of newborns' hematocrit on Tg determination. A commercially available ELISA Tg assay was adapted for use on DBS. DBS-Tg in cord blood were measured in 209 newborns delivered from healthy euthyroid pregnant women. Sensitivity, linearity, repeatability, and intermediate fidelity were determined using the appropriate standards and quality control materials. The limit of detection (LoD) of the DBS-Tg assay was 2.4 µg/L, and the limit of quantification (LoQ) was 5.8 µg/L. Repeatability and intermediate fidelity were 7.7-8.3% and 11.0-11.2%, respectively. The median cord plasma Tg and DBS-Tg values in newborns were not significantly different, 30.2 (21.3-44.4) µg/L and 31.6 (19.3-48.7) µg/L (p=0.48) with the ELISA respectively, and 76.5 (40.0-101.5) µg/L with the Elecsys assay with an R=0.88. DBS-Tg concentrations decrease with increasing hematocrit values (p<0.05). DBS-Tg values were stable at a concentration of 25 µg/L for 12 months at -20ºC and 4ºC. This DBS-Tg assay demonstrated good analytical performances over a wide range of Tg concentrations, suggesting it is well suited to detecting variations in Tg concentrations. Studies comparing populations with different prevalence of anemia should consider the effect of hematocrit on DBS-Tg determination. The availability of a DBS-Tg assay for newborns makes it possible to integrate iodine status monitoring with newborn screening for inherited metabolic diseases.

MicroRNAs in Congenital Diaphragmatic Hernia: Insights into Prenatal and Perinatal Biomarkers and Altered Molecular Pathways: microRNAs in Congenital Diaphragmatic Hernia for Pathway Analysis and Prognostic Biomarkers

Congenital diaphragmatic hernia (CDH) is characterized by a diaphragmatic defect, leading to herniation of abdominal organs into the chest, lung compression, and impaired lung development, often resulting in pulmonary hypertension and lung hypoplasia. Prenatal imaging techniques like ultrasound and MRI provide anatomical predictors of outcomes, but their limitations necessitate novel biomarkers for better prognostic accuracy. This study aims to identify unique circulating maternal, fetal, and neonatal microRNAs (miRNAs) that can distinguish CDH pregnancies from healthy controls and assess their potential as markers of disease severity. We conducted a prospective study involving third-trimester maternal blood, amniotic fluid, cord blood, and neonatal blood samples from pregnancies complicated by CDH and healthy controls. miRNA expression was analyzed using RNA-sequencing, and random forest analysis identified miRNAs distinguishing CDH survivors from non-survivors. Pathway enrichment analyses were performed to explore the biological relevance of differentially expressed miRNAs. Significant miRNA expression differences were observed between CDH and control samples across all sample types. In infant blood, 148 miRNAs were up-regulated, and 36 were down-regulated in CDH cases. Pathway analysis revealed that dysregulated miRNAs in CDH targeted pathways related to protein binding, transcription regulation, and signaling pathways implicated in pulmonary hypertension and lung hypoplasia. Random forest analysis identified miRNAs in maternal blood (miR-7850-5p_L-1R+2, miR-942-3p, and miR-197-3p) that distinguished CDH survivors from non-survivors, with an ROC area under the curve of 1.0. Circulating miRNAs in maternal blood offer promising biomarkers for predicting CDH outcomes. miRNAs from infant blood provide mechanistic insights and potential targets for therapeutic intervention in critical pathways of pulmonary hypertension and lung hypoplasia. Further studies with larger cohorts are needed to validate these findings and explore the clinical application of miRNA biomarkers in CDH management.

Hairy Cell Leukemia Following Acute Myeloid Leukemia, Concomitant or Secondary?

A 62-year-old man diagnosed with acute myeloid leukemia (AML) showed limited responses to two courses of azacitidine (AZA)+Venetoclax (VEN) therapy. Twenty days after being transferred to our hospital, flow cytometry with broad antigen coverage and mutation analysis confirmed the presence of a second malignancy, hairy cell leukemia (HCL). Following haploidentical combined umbilical cord blood transplantation, the patient achieved complete remission (CR) for both AML and HCL. This CR has been maintained for the past 14 months. Patients with dual hematologic malignancies may not respond well to conventional therapy regimens. Early initiation of hematopoietic stem cell transplantation is beneficial for improving prognosis and extending overall survival.

Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.

Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM. An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies. NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice. NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.

The Frequency of Intraventricular Hemorrhage and its Risk Factors.

Intraventricular hemorrhage (IVH) (is the most prevalent type of cerebrovascular accident in premature infants, which can result in lasting neurological complications. The aim of this study was to ascertain the frequency of IVH and its associated risk factors within our particular context. This cross-sectional study was carried out in a tertiary neonatal intensive care unit of a maternal and neonatal hospital from September 2018 to August 2019. Premature infants under 34 weeks of age and with birth weight < 1500 grams who did not have significant congenital anomalies participated in the study. A brain ultrasound was performed by a sonologist during the first week. The infants were subsequently categorized into two groups: those with and without IVH. A comparative analysis was conducted using the chi-square test and logistic regression. A significance level of p<0.05 was considered statistically significant. Of the 205 premature infants who completed the study, IVH was reported in 107 cases (52.1%), of which 97.3% of ventricular hemorrhages were grade I and II and 2.7% accounted for severe bleeding (grade III and IV). Gestational age less than 28 weeks, weight less than 1000 g, vaginal delivery, asphyxia and resuscitation, history of intubation and mechanical ventilation, cord blood acidity, dopamine infusion, and history of fever and chorioamnionitis in the mother have been found to be significantly associated with increased risk of IVH (p<0.001). Antenatal corticosteroids decreased the risk (OR=10.63). In this study, IVH has been found to be common in infants under 1500 g of weight, but the severe form was low in frequency and was observed significantly in high-risk pregnancies.

Specific antibody responses to Qβ-displayed Plasmodium falciparum-derived UB05 and MSP3 proteins in mother-neonate couples.

Malaria blood-stage parasite is a critical pathogenic stage responsible for serious adverse outcomes in pregnant women and their neonates. Immunoglobulin G (IgG) antibody responses specific to various asexual blood-stage antigens were well reported in non-pregnant individuals. However, little is still known during placental malaria. To assess the antibody responses specific to Plasmodium falciparum-derived MSP3 and UB05 malaria vaccine candidates in mother-neonate couples, mother's peripheral blood and neonate's cord blood samples were collected at delivery. After malaria diagnostic, plasma levels of IgG and IgG subclass responses specific to UB05, MSP3 and UB05-MSP3 were determined using ELISA. As outcomes, both mothers and neonates had significantly higher IgG responses to UB05 and UB05-MSP3 compared to anti-MSP3 IgG (p < 0.05), irrespective of malaria status. Significant negative correlations were observed between IgG levels specific to the three antigens and parasitaemia (p < 0.01). Anti-UB05 and anti-UB05-MSP3 IgG levels in neonates showed a significant positive correlation with the corresponding mothers' antibodies (rs = 0.25 with p = 0.04; rs = 0.31 with p = 0.01, respectively). UB05MSP3-specific IgG3 and IgG1 subclass responses were significantly higher than the IgG4 subclass (p < 0.01). The neonates IgG1 and IgG3 levels positively correlated with the corresponding antibody subclasses of mothers. These findings suggest an association between UB05 and UB05-MSP3-specific antibody responses and malaria control during pregnancy. Maternal-foetal transfer of MSP3 and UB05-specific IgG occurs during pregnancy, suggesting the interest in the future malaria vaccination strategies in pregnant women to generate early protective immunity in baby against malaria.

Association of 25(OH)-Vitamin D3 Serum Concentrations and Vitamin D Receptor Gene Variants with the Risk of Idiopathic Spontaneous Preterm Birth in the Croatian Population.

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls (p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed.

Identification of CD141+vasculogenic precursor cells from human bone marrow and their endothelial engagement in the arteriogenesis by co-transplantation with mesenchymal stem cells

BackgroundCritical limb ischemia (CLI) is a condition characterized by insufficient blood flow to the lower limbs, resulting in severe ischemia and potentially leading to amputation. This study aims to identify novel vasculogenic precursor cells (VPCs) in human bone marrow and evaluate their efficacy in combination with bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of CLI.MethodsEx vivo cultured VPCs and BM-MSCs from bone marrow were characterized and their effects on neovascularization and long-term tissue regeneration were tested in a mouse CLI model.ResultsVPCs, expressing high levels of hepatocyte growth factor and c-MET, were identified from human bone marrow aspirates. These cells exhibited strong vasculogenic capacity in vitro but possessed a cellular phenotype distinct from those of previously reported endothelial precursor cells in circulation or cord blood. They also expressed most surface markers of BM-MSCs and demonstrated multipotent differentiation ability. Screening of 376 surface markers revealed that VPCs uniquely display CD141 (thrombomodulin). CD141+VPCs are present in BM aspirates as a rare population and can be expanded ex vivo with a population doubling time of approximately 20 h, generating an elaborate vascular network even under angiogenic factor-deficient conditions and recruiting BM-MSCs to the network as pericyte-like cells. Intramuscular transplantation of a combination of human CD141+VPCs and BM-MSCs at a ratio of 2:1 resulted in limb salvage, blood flow recovery, and regeneration of large vessels in the femoral artery-removed CLI model, with an efficacy superior to that of singular transplantation. Importantly, large arteries and arterioles in dual cell transplantation expressed human CD31 in the intima and human α-smooth muscle actin in media layer at 4 and 12 weeks, likely indicating their lineage commitment to endothelial cells and vascular smooth muscle, respectively, in vivo.ConclusionDual-cell therapy using BM-derived CD141+ VPCs and BM-MSCs holds potential for further development in clinical trials to treat peripheral artery disease and diabetic ulcers.

The levels of oxidative stress markers in maternal and umbilical cord blood of pregnant women with diabetes mellitus in terms of blood flow redistribution in the fetal venous system

The levels of oxidative stress markers in maternal and umbilical cord blood of pregnant women with diabetes mellitus in terms of blood flow redistribution in the fetal venous system

Development and validation of an UPLC-ESI-MS/MS method for simultaneous quantification of antineoplastic agents and their metabolites in human plasma after unintentional exposure.

Cyclophosphamide, daunorubicin, epirubicin, doxorubicin and paclitaxel are commonly used drugs in cancer treatment. However, there are no methods available enabling simultaneous measurement of these compounds and their metabolites in human plasma. Our aim was to develop and validate a sensitive method for simultaneous quantification of multiple antineoplastic drugs and their major metabolites in plasma. Solid phase extraction with Oasis PRiME HLB cartridges was used for sample clean-up. The samples were separated on an Acquity UPLC BEH C18 column, ionised by electrospray ionisation and detected with tandem mass spectrometry. The method was validated based on selectivity, extraction efficiency, matrix effect, process efficiency, linearity, sensitivity, precision and accuracy. The established LLOQs were 0.05ng/mL (cyclophosphamide), 30ng/mL (4-oxo-cyclophosphamide), 0.3ng/mL (doxorubicin, daunorubicinol), 0.7ng/mL (epirubicin, epirubicinol, doxorubicinol), 1ng/mL (daunorubicin and paclitaxel) and 5ng/mL (6-alpha-hydroxypaclitaxel). Afterwards, the method was tested in a real-life, unintentional exposure setting. Twenty-two plasma samples of matched maternal and cord blood pairs from pregnant cancer patients treated with chemotherapy were analysed. This resulted in two positive samples, with cyclophosphamide concentrations up to 0.37ng/mL. The validated method is now ready to be applied in the field.

Association between maternal vitamin D status during late pregnancy and acute lower respiratory tract infections and acute diarrheal disease during infancy – A cohort study

BackgroundAcute lower respiratory tract infection (ALRI) and acute diarrheal disease (ADD) are the leading causes of mortality in children globally. There is emerging evidence of an association between maternal hypovitaminosis D and ALRI/ADD during infancy. ObjectiveTo determine whether maternal hypovitaminosis D (25(OH)D [< 20 ng/ml] during late pregnancy is associated with increased risk of ALRI/ADD in their offspring during infancy. MethodsThis South Indian hospital-based, ambispective cohort study included 140 mother-baby dyads with known maternal vitamin D status before delivery in late third trimester (72 mothers with hypovitaminosis D and 68 mothers with adequate vitamin D level). Babies with cord blood vitamin D deficiency were treated as per consensus guidelines and those with adequate levels were supplemented with 400 IU vitamin D daily for 1 year. All infants were followed up at 6,10,14 weeks and 6, 9, 12 months for the occurrence, frequency, and severity of ALRI (pneumonia, bronchiolitis, viral induced wheezing) and ADD. ResultsOverall incidence of ALRI was 0.23 per child year during infancy. Incidence of ALRI was 0.12 per child year in adequate maternal vitamin D group versus 0.32 per child year in maternal hypovitaminosis D group (p value=0.024) and that of bronchiolitis/viral wheeze was 0.07 per child year in adequate maternal vitamin D group versus 0.21 per child year in maternal hypovitaminosis D group (p value=0.047). Cox regression analysis with maternal hypovitaminosis D level as predictor variable, adjusted for gestational age at birth and other covariates, revealed a hazard ratio of 3.18 (95% CI: 1.17 – 8.65, p = 0.023) and 3.63 (95% CI 1.36-9.65, p=0.010) for ALRI and ADD respectively. No increased risk for occurrence of pneumonia was observed and none had severe pneumonia. ConclusionMaternal hypovitaminosis D is associated with increased risk of ALRI and ADD in their babies during infancy. Routine screening of pregnant women at risk for hypovitaminosis D and supplementation based on 25(OH)D level may decrease the burden of ALRI, for which further studies are needed.