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Placenta Feb 2024Ensuring adequate fetal oxygenation is an essential aim of fetal monitoring. The purpose of this study was to establish a basic technique for real-time measurement of...
INTRODUCTION
Ensuring adequate fetal oxygenation is an essential aim of fetal monitoring. The purpose of this study was to establish a basic technique for real-time measurement of blood oxygen saturation of the placenta by photoacoustic (PA) technique as a new fetal monitoring method.
METHODS
The hypoxia model established in our previous study was applied to 7 pregnant rabbits. Three phases were induced: normal phase, hypoxia phase, and recovery phase. Three methods were simultaneously used for real-time fetal monitoring: fetal heat rate (FHR) monitoring, oxygen saturation (SO) measurement by near-infrared spectroscopy (SO), and placenta SO measured by PA technique (SO). The maternal hypoxia was assessed by skin SO measured by PA technique (SsO), and arterial blood SO by blood gas analysis (SaO).
RESULTS
The average of SO in normal phase was 52.6 ± 13.9 %. The averages of SO, SO, and SO in the seven rabbits changed in parallel from the normal phase to hypoxia phase. In the recovery phase, the SO rose in parallel with recovery of SaO. There was lag in increase of the FHR compared to the change in the other values. In the detailed analysis of PA signals from the labyrinth and decidua, a unique change in oxygen saturation was seen in one case.
DISCUSSION
Results of this study showed that sensitivity of our novel PA technique in detecting tissue hypoxia was similar to near-infrared spectroscopy (NIRS). As an advantage, unlike NIRS, monitoring with PA technique was unaffected by ischemia and surface changes in oxygen saturation because of its higher spatial resolution. We conclude that PA technique provides more accurate information about fetal blood placenta than NIRS. Ultrasound imaging, combined with oxygen saturation monitoring by PA technique, would improve fetal monitoring and fetal diagnosis in the future.
Topics: Animals; Rabbits; Female; Pregnancy; Oxygen; Placenta; Oxygen Saturation; Hypoxia; Fetal Monitoring
PubMed: 38241840
DOI: 10.1016/j.placenta.2024.01.005 -
Frontiers in Cellular and Infection... 2023Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate...
BACKGROUND
Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B (GBS, ) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints.
METHODS
Twelve nonhuman primates (pigtail macaques, ) received a choriodecidual inoculation of either: 1) 1-5 X 10 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔ, N=4); 2) an isogenic/nonpigmented strain (GBS ΔΔ, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests.
RESULTS
Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1β, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05).
CONCLUSION
Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.
Topics: Infant, Newborn; Animals; Humans; Pregnancy; Female; Streptococcus agalactiae; Placenta; Immune Checkpoint Proteins; Up-Regulation; Premature Birth; Cesarean Section; Streptococcal Infections; Primates
PubMed: 38239507
DOI: 10.3389/fcimb.2023.1299644 -
Scientific Reports Jan 2024The elimination of hazardous industrial pollutants from aqueous solutions is an emerging area of scientific research and a worldwide problem. An efficient catalyst,...
The elimination of hazardous industrial pollutants from aqueous solutions is an emerging area of scientific research and a worldwide problem. An efficient catalyst, Ag-CuO was synthesized for the degradation of methylene blue, the chemical sensing of ammonia. A simple novel synthetic method was reported in which new plant material Capparis decidua was used for the reduction and stabilization of the synthesized nanocatalyst. A Varying amount of Ag was doped into CuO to optimize the best catalyst that met the required objectives. Through this, the Ag-CuO nanocomposite was characterized by XRD, SEM, HR-TEM, EDX, and FTIR techniques. The mechanism of increased catalytic activity with Ag doping involves the formation of charge sink and suppression of drop back probability of charge from conduction to valance band. Herein, 2.7 mol % Ag-CuO exhibited better catalytic activities and it was used through subsequent catalytic experiments. The experimental conditions such as pH, catalyst dose, analyte initial concentration, and contact time were optimized. The as-synthesized nanocomposite demonstrates an excellent degradation efficacy of MB which is 97% at pH 9. More interestingly, the as-synthesized catalyst was successfully applied for the chemical sensing of ammonia even at very low concentrations. The lower limit of detection (LLOD) also called analytic sensitivity was calculated for ammonia sensing and found to be 1.37 ppm.
PubMed: 38238395
DOI: 10.1038/s41598-024-51391-2 -
Cell Stem Cell Feb 2024In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is...
In humans, balanced invasion of trophoblast cells into the uterine mucosa, the decidua, is critical for successful pregnancy. Evidence suggests that this process is regulated by uterine natural killer (uNK) cells, but how they influence reproductive outcomes is unclear. Here, we used our trophoblast organoids and primary tissue samples to determine how uNK cells affect placentation. By locating potential interaction axes between trophoblast and uNK cells using single-cell transcriptomics and in vitro modeling of these interactions in organoids, we identify a uNK cell-derived cytokine signal that promotes trophoblast differentiation at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in regulating blood flow, nutrients, and inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings suggest mechanisms on how optimal immunological interactions between uNK cells and trophoblast enhance reproductive success.
Topics: Pregnancy; Female; Humans; Extravillous Trophoblasts; Uterus; Placentation; Trophoblasts; Killer Cells, Natural
PubMed: 38237587
DOI: 10.1016/j.stem.2023.12.013 -
Pediatric and Developmental Pathology :... 2024A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging...
A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging (MRI) revealed bilateral multicystic uterine adnexa. Exploratory laparotomy was performed at 17 weeks of gestation and bilateral serous ovarian adenocarcinoma FIGO stage IIIC was diagnosed. Complete cytoreductive surgery (CRS) was not feasible at that moment. Nine days after the exploratory laparotomy, immature rupture of membranes and contractions occurred and she delivered a premature boy after 19 weeks of gestation. Pathological examination of the placenta revealed that her ovarian cancer metastasized to the membranes. We describe the first case of ovarian cancer metastasized to the decidua of the placental membranes with histological, immunohistochemical, and molecular confirmation. This case highlights the importance of conscientious evaluation of placenta and membranes in pregnant women with ovarian cancer.
Topics: Humans; Female; Ovarian Neoplasms; Pregnancy; Adult; Pregnancy Complications, Neoplastic; Decidua; Cystadenocarcinoma, Serous; Placenta; Biomarkers, Tumor
PubMed: 38221679
DOI: 10.1177/10935266231222180 -
PLoS Pathogens Jan 2024Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in...
Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in better placentation and fetus-growth, hence termed pregnancy trained dNKs (PTdNKs). Here we show that PTdNKs provide increased protection of the fetus from Fusobacterium nucleatum (FN) infection. We demonstrate that PTdNKs secrete elevated amounts of the bacteriocidal protein granulysin (GNLY) upon incubation with FN compared to dNKs derived from first pregnancies, which leads to increased killing of FN. Furthermore, we showed mechanistically that the GNLY secretion is mediated through the interaction of the FN's Fap2 protein with Gal-GalNAc present on PTdNKs. Finally, we show in vivo, using GNLY-tg mice that enhanced protection of the fetuses from FN infection is observed, as compared to wild type and that this enhance protection is NK cell dependent. Altogether, we show a new function for PTdNKs as protectors of the fetus from bacterial infection.
Topics: Pregnancy; Female; Mice; Animals; Decidua; Fusobacterium nucleatum; Killer Cells, Natural
PubMed: 38215172
DOI: 10.1371/journal.ppat.1011923 -
BMC Plant Biology Jan 2024The species composition of tree stands plays an important role in shaping the properties of forest soils. The aim of our research was to determine the influence on soil...
BACKGROUND
The species composition of tree stands plays an important role in shaping the properties of forest soils. The aim of our research was to determine the influence on soil properties of the root systems of six species of trees which form forest stands in the temperate climatic zone. The research covered areas including six tree species - Scots pine (Pinus sylvestris L.), European larch (Larix deciduas Mill.), English oak (Quercus robur L.), English ash (Fraxinus excelsior L.), European beech (Fagus sylvatica L.) and European hornbeam (Carpinus betulus L.). In our study, we determined the characteristics of the roots and the amount of carbon excreted alongside their exudates. Enzymatic activity, and the composition and diversity of the fungi and bacteria, were also determined in addition to the basic physicochemical properties of the soil samples.
RESULTS
A strong relationship between the root characteristics and soil properties, including the pH, basic cation content and phosphorus content, was confirmed. In addition, the enzymatic activity of phosphatase, β-glucosidase, N-acetyl-β-D-glucosaminidase and β-D-cellobiosidase were positively correlated with the root characteristics. The study on soil bacteria across different tree species revealed Proteobacteria and Actinobacteriota to be the most abundant phylum. Fungal analysis showed Basidiomycota and Ascomycota as the dominant phyla. Ascomycota dominated in hornbeam and oak soils. Mortierellomycota was remarkably more present in pine soil.
CONCLUSIONS
This analysis of root systems and soil properties confirmed the distinctness of ash stands, which were also more abundant in various microorganisms. It was also found that soils affected by different tree species were characterised by varied fungal and bacterial composition. The ash had particularly beneficial impact on soil microbiota.
Topics: Ecosystem; Trees; Soil; Forests; Pinus sylvestris; Ascomycota; Fagus; Quercus; Exudates and Transudates; Soil Microbiology
PubMed: 38212695
DOI: 10.1186/s12870-024-04724-2 -
Stem Cells (Dayton, Ohio) Apr 2024Acute graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication following allogeneic hematopoietic cell transplantation (HCT)....
Acute graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication following allogeneic hematopoietic cell transplantation (HCT). Mesenchymal stromal cells (MSCs), rare precursors found in all body tissues, possess immunosuppressive properties and can inhibit alloreactivity both in vitro and in vivo. Two decades ago, we introduced bone marrow-derived (BM) MSCs as a novel therapy for acute GVHD. While some patients responded to BM-MSCs, the response was not universal. Commercially available BM-MSCs are now used for acute GVHD treatment in Canada, Japan, and New Zealand. The fetus is protected from the mother's immune system by the placenta, and our research found that placenta-derived decidua stromal cells (DSCs) offer a stronger immunosuppressive effect than other sources of stromal cells. Safety studies in rabbits, rats, mice, and humans have shown negligible or no side effects from BM-MSCs or DSCs. In a phase I/II trial for severe acute GVHD, we treated 21 patients (median age, 49 years; range 1.6-72 years) with severe biopsy-proven gastrointestinal acute GVHD. The median cell dose of DSCs was 1.2 × 106 (range 0.9-2.9) cells/kg body weight, with a median of 2 (range 1-6) infusions given 1 week apart. The cell viability of DSCs was 93% (range, 69%-100%), and the median cell passage number was 4 (range, 2-4). All patients responded, with a complete response of acute GVHD in 11 patients and partial response in 10 and 1-year survival of 81%. Randomized trials are needed to prove the superiority of DSCs compared to ruxolitinib and/or other novel immunosuppressive therapies.
Topics: Animals; Female; Humans; Mice; Middle Aged; Rabbits; Rats; Acute Disease; Decidua; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Immunosuppressive Agents; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Stromal Cells; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Aged; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic
PubMed: 38204331
DOI: 10.1093/stmcls/sxae003 -
Journal of Neuroinflammation Jan 2024Preterm birth is often associated with chorioamnionitis and leads to increased risk of neurodevelopmental disorders, such as autism. Preterm birth can lead to cerebellar...
BACKGROUND
Preterm birth is often associated with chorioamnionitis and leads to increased risk of neurodevelopmental disorders, such as autism. Preterm birth can lead to cerebellar underdevelopment, but the mechanisms of disrupted cerebellar development in preterm infants are not well understood. The cerebellum is consistently affected in people with autism spectrum disorders, showing reduction of Purkinje cells, decreased cerebellar grey matter, and altered connectivity.
METHODS
Preterm rhesus macaque fetuses were exposed to intra-amniotic LPS (1 mg, E. coli O55:B5) at 127 days (80%) gestation and delivered by c-section 5 days after injections. Maternal and fetal plasma were sampled for cytokine measurements. Chorio-decidua was analyzed for immune cell populations by flow cytometry. Fetal cerebellum was sampled for histology and molecular analysis by single-nuclei RNA-sequencing (snRNA-seq) on a 10× chromium platform. snRNA-seq data were analyzed for differences in cell populations, cell-type specific gene expression, and inferred cellular communications.
RESULTS
We leveraged snRNA-seq of the cerebellum in a clinically relevant rhesus macaque model of chorioamnionitis and preterm birth, to show that chorioamnionitis leads to Purkinje cell loss and disrupted maturation of granule cells and oligodendrocytes in the fetal cerebellum at late gestation. Purkinje cell loss is accompanied by decreased sonic hedgehog signaling from Purkinje cells to granule cells, which show an accelerated maturation, and to oligodendrocytes, which show accelerated maturation from pre-oligodendrocytes into myelinating oligodendrocytes.
CONCLUSION
These findings suggest a role of chorioamnionitis on disrupted cerebellar maturation associated with preterm birth and on the pathogenesis of neurodevelopmental disorders among preterm infants.
Topics: Infant, Newborn; Female; Infant; Animals; Humans; Pregnancy; Hedgehog Proteins; Macaca mulatta; Chorioamnionitis; Premature Birth; Escherichia coli; Infant, Premature; Cerebellum; RNA, Small Nuclear
PubMed: 38200558
DOI: 10.1186/s12974-024-03012-y -
Scientific Reports Jan 2024Villitis of unknown etiology (VUE) is a prevalent inflammatory pathology of the placenta characterized by infiltration of maternal T cells and accumulation of fetal...
Villitis of unknown etiology (VUE) is a prevalent inflammatory pathology of the placenta characterized by infiltration of maternal T cells and accumulation of fetal macrophages into chorionic villi. VUE is associated with a variety of adverse clinical outcomes, including fetal growth restriction and fetal demise. Evaluation of the phenotypic and functional differences between two immune cell types associated with this pathology, namely T cells and macrophages, was completed to gain a deeper understanding of the immuno-pathogenesis of VUE. GeoMx Digital Spatial Profiling was performed on placental tissue from 4 high grade VUE cases and 4 controls with no underlying pathology. Placental tissues were fluorescently labeled with CD3 and CD68 antibodies and oligo-conjugated antibodies against 48 protein targets. Overall, T cells in VUE exhibited upregulated markers of activation, memory, and antigen experience compared to controls and were altered based on placental location (villi vs. decidua). Additionally, villous macrophages in VUE upregulated costimulatory and major histocompatibility complex class I and II molecules compared to controls and macrophage subtypes in the decidua. Data herein provides new mechanistic insights into T cell and macrophage biology in VUE which contribute to this abnormal immune response to pregnancy.
Topics: Pregnancy; Female; Humans; Placenta; Proteomics; T-Lymphocytes; Chorioamnionitis; Macrophages
PubMed: 38195710
DOI: 10.1038/s41598-024-51545-2