Identification of the acrylate porphyrin S-411 from meconium.
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ABSTRACT:
SUBMITTER: French J
PROVIDER: S-EPMC1179610 | biostudies-other | 1970 Nov
REPOSITORIES: biostudies-other
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Project description:OBJECTIVE:This study aims to determine whether fetal meconium passage is associated with autism. STUDY DESIGN:This retrospective birth cohort analysis of 9?945?896 children born in California 1991 to 2008 linked discharge diagnosis and procedure codes for prenatal stressors, meconium-stained amniotic fluid (MSAF) and meconium aspiration syndrome (MAS) with autism diagnoses for 47?277 children through 2012. We assessed the relative risk of autism by meconium status using logistic regression, adjusting for demographic and clinical features. RESULTS:Children exposed to meconium (MSAF and MAS) were more likely to be diagnosed with autism in comparison with unexposed children (0.60% and 0.52%, vs 0.47%, respectively). In adjusted analyses, there was a small increase in autism risk associated with MSAF exposure (adjusted relative risk (aRR) 1.18, 95% confidence interval (CI) 1.12 to 1.25), and a marginal association that failed to achieve significance between MAS and autism (aRR 1.08, 95% CI 0.98 to 1.20). CONCLUSION:Resuscitation of neonates with respiratory compromise from in utero meconium exposure may mitigate long-term neurodevelopmental damage.
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Project description:All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways, to accumulate heme intermediates, i.e., porphyrins. We coined this essential metabolic rewiring ‘porphyrin overdrive’ and determined that it is cancer-essential and cancer-specific. Among the major drivers are genes encoding mid-step enzymes governing the production of heme intermediates. CRISPR/Cas9 editing to engineer leukemia cell lines with impaired heme biosynthetic steps confirmed our whole genomic data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation. While porphyrin overdrive is absent in differentiated cells or somatic stem cells, it is present in patient-derived tumor progenitor cells, demonstrated by single cell RNAseq, and in early embryogenesis. In conclusion, we identified a dependence of cancer cells on non-homeostatic heme metabolism, and we targeted this cancer metabolic vulnerability with a novel “bait-and-kill” strategy to eradicate malignant cells.
2024-04-17 | GSE263829 | GEO
Project description:Viable bacterial colonization is highly limited in the human intestine in utero
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Project description:The purpose of this work was to investigate the effect of multifunctionality on material properties of synthetic polymer aerogels. For this purpose, we present the synthesis and characterization of monolithic dendritic-type urethane-acrylate monomers based on an aliphatic/flexible (Desmodur N3300), or an aromatic/rigid (Desmodur RE) triisocyanate core. The terminal acrylate groups (three at the tip of each of the three branches, nine in total) were polymerized with 2,2'-azobis(isobutyronitrile) (AIBN) via free radical chemistry. The resulting wet-gels were dried with supercritical fluid (SCF) CO?. Aerogels were characterized with ATR-FTIR and solid-state 13C NMR. The porous network was probed with N?-sorption and scanning electron microscopy (SEM). The thermal stability of aerogels was studied with thermogravimetric analysis (TGA). Most aerogels were macroporous materials (porosity > 80%), with high thermal stability (up to 300 °C). Aerogels were softer at low monomer concentrations and more rigid at higher concentrations. The material properties were compared with those of analogous aerogels bearing only one acrylate moiety at the tip of each branch and the same cores, and with those of analogous aerogels bearing norbornene instead of acrylate moieties. The nine-terminal acrylate-based monomers of this study caused rapid decrease of the solubility of the growing polymer and made possible aerogels with much smaller particles and much higher surface areas. For the first time, aliphatic/flexible triisocyanate-based materials could be made with similar properties in terms of particle size and surface areas to their aromatic/rigid analogues. Finally, it was found that with monomers with a high number of crosslinkable groups, material properties are determined by multifunctionality and thus aerogels based on 9-acrylate- and 9-norbornene-terminated monomers were similar. Materials with aromatic cores are carbonizable with satisfactory yields (20?30% w/w) to mostly microporous materials (BET surface areas: 640?740 m² g-1; micropore surface areas: 360?430 m² g-1).
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Project description:Forty two babies with Meconium aspiration syndrome managed in neonatal intensive care unit of a service hospital were analysed. Incidence was 1.7 per cent. Twelve babies were delivered by caserean section and 30 babies by vaginal route. Seventeen deliveries were conducted by team of gynaecologists, pediatrician and nursing staff whereas 25 deliveries were conducted by nursing staff alone. Out of total babies with meconium aspiration syndrome, thin meconium detected in 9 and thick meconium detected in 33 babies during delivery. Five babies were preterm and none were less than 35 weeks of gestation. Pneumonia detected on right side in 24 patients, on left side in 6, and both sides in 12 patients. Twenty seven babies had asphyxia at birth, 13 babies had seizure and 6 babies had air leak syndrome and overall mortality was 13 (31%).
| S-EPMC5531208 | biostudies-other
Project description:BackgroundMeconium-stained amniotic fluid is observed in approximately 10-15% of all deliveries; however, only 5% of neonates with meconium-stained amniotic fluid develop meconium aspiration syndrome (MAS). Although foetal distress and subsequent sympathetic stimulation have been considered as the primary upstream events of MAS, this clinical complication sometimes occurs due to other pathologies, such as intraamniotic inflammation. The aim of this study was to investigate whether the incidence of MAS is associated with the presence of funisitis and chorioamnionitis in term neonates with meconium-stained amniotic fluid.MethodsBetween April 2013 and March 2015, a total of 95 term neonates with meconium-stained amniotic fluid, who were hospitalized at a neonatal intensive care unit, were enrolled in the study. The placenta and umbilical cord were histopathologically examined. Clinical variables and histopathological findings associated with the incidence of MAS were studied.ResultsA total of 36 neonates developed MAS. Univariate logistic regression analysis revealed that a heavier birth weight, male sex, 1-min Apgar score ≤ 7, funisitis (but not chorioamnionitis), and elevated acute-phase inflammatory reaction score were associated with increased incidence of MAS (all p < 0.05). The multivariate model comprised funisitis (OR = 5.03, 95% CI [1.63-15.5], 1-min Apgar score ≤ 7 (OR = 2.74, 95% CI [1.06-7.09], and male sex (OR = 3.4, 95% CI [1.24-9.34].ConclusionIn neonates with meconium-stained amniotic fluid, funisitis, as well as low 1-min Apgar score and male sex, was identified as an independent variable for MAS development. Intraamniotic inflammation might be involved in the pathological mechanisms of MAS.
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Project description:Meconium constitutes infants' first bowel movements postnatally. The consistency and microbial load of meconium are different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with negative health outcomes, but its composition is not well described, especially in preterm infants. Here, we characterized the meconium microbiomes from 330 very preterm infants (gestational ages 28 to 32 weeks) from 15 hospitals in Germany and in fecal samples from a subset of their mothers (N = 217). Microbiome profiles were compiled using 16S rRNA gene sequencing with negative and positive controls. The meconium microbiome was dominated by Bifidobacterium, Staphylococcus, and Enterococcus spp. and was associated with gestational age at birth and age at sample collection. Bifidobacterial abundance was negatively correlated with potentially pathogenic genera. The amount of bacterial DNA in meconium samples varied greatly across samples and was associated with the time since birth but not with gestational age or hospital site. In samples with low bacterial load, human mitochondrial sequences were highly amplified using commonly used, bacterial-targeted 16S rRNA primers. Only half of the meconium samples contained sufficient bacterial material to study the microbiome using a standard approach. To facilitate future meconium studies, we present a five-level scoring system ("MecBac") that predicts the success of 16S rRNA bacterial sequencing for meconium samples. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies. IMPORTANCE Meconium is present in the intestines of infants before and after birth and constitutes their first bowel movements postnatally. The consistency, composition and microbial load of meconium is largely different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with short-term and long-term negative health outcomes, but its composition is not yet well described, especially in preterm infants. We provide a characterization of the microbiome structure and composition of infant meconium and maternal feces from a large study cohort and propose a method to evaluate meconium samples for bacterial sequencing suitability. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies.
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Project description:ObjectiveCancer diagnosis during pregnancy occurs in 1 out of 1000 pregnancies with common malignancies including breast and hematological cancers. Fetal exposure to currently utilized agents is poorly described. We directly assessed fetal exposure by screening meconium from 23 newborns whose mothers had undergone treatment for cancer during pregnancy.Study designMeconium was collected from newborns whose mothers were diagnosed with cancer during pregnancy and underwent chemotherapy in the second or third trimester as part of the Cancer and Pregnancy Registry. We conducted screening of 23 meconium samples for chemotherapeutics and known metabolites of chemotherapeutics by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Putative identification of paclitaxel and/or its metabolites was made in 8 screened samples. In positively screened samples, we quantified paclitaxel, 3'-p-hydroxypaclitaxel, and 6?-hydroxypaclitaxel by stable isotope dilution-LC-HRMS.ResultsMean (standard deviation) levels of paclitaxel in positively screened samples were 399.9 (248.6) pg/mg in meconium samples from newborn born to mothers that underwent chemotherapy during pregnancy. 3'-p-hydroxypaclitaxel and 6?-hydroxypaclitaxel mean levels were 105.2 (54.6) and 113.4 (48.9) pg/mg meconium, respectively.ConclusionIntact paclitaxel, 3'-p-hydroxypaclitaxel, and 6?-hydroxypaclitaxel were detected in meconium, providing unambiguous confirmation of human fetal exposure. Variability in meconium levels between individuals may indicate a potential for reducing fetal exposure based on timing, dosing, and individual characteristics. This preliminary study may provide an approach for examining the effects of cancer diagnosis during pregnancy on other outcomes by providing a measure of direct fetal exposure.
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