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International Journal of Molecular... Feb 2024Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps...
Intravenous Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Spinal Cord Injury by Regulating Neutrophil Extracellular Trap Formation through Exosomal miR-125a-3p.
Spinal cord injury (SCI) leads to devastating sequelae, demanding effective treatments. Recent advancements have unveiled the role of neutrophil extracellular traps (NETs) produced by infiltrated neutrophils in exacerbating secondary inflammation after SCI, making it a potential target for treatment intervention. Previous research has established that intravenous administration of stem cell-derived exosomes can mitigate injuries. While stem cell-derived exosomes have demonstrated the ability to modulate microglial reactions and enhance blood-brain barrier integrity, their impact on neutrophil deactivation, especially in the context of NETs, remains poorly understood. This study aims to investigate the effects of intravenous administration of MSC-derived exosomes, with a specific focus on NET formation, and to elucidate the associated molecular mechanisms. Exosomes were isolated from the cell supernatants of amnion-derived mesenchymal stem cells using the ultracentrifugation method. Spinal cord injuries were induced in Sprague-Dawley rats (9 weeks old) using a clip injury model, and 100 μg of exosomes in 1 mL of PBS or PBS alone were intravenously administered 24 h post-injury. Motor function was assessed serially for up to 28 days following the injury. On Day 3 and Day 28, spinal cord specimens were analyzed to evaluate the extent of injury and the formation of NETs. Flow cytometry was employed to examine the formation of circulating neutrophil NETs. Exogenous miRNA was electroporated into neutrophil to evaluate the effect of inflammatory NET formation. Finally, the biodistribution of exosomes was assessed using Cu-labeled exosomes in animal positron emission tomography (PET). Rats treated with exosomes exhibited a substantial improvement in motor function recovery and a reduction in injury size. Notably, there was a significant decrease in neutrophil infiltration and NET formation within the spinal cord, as well as a reduction in neutrophils forming NETs in the circulation. In vitro investigations indicated that exosomes accumulated in the vicinity of the nuclei of activated neutrophils, and neutrophils electroporated with the miR-125a-3p mimic exhibited a significantly diminished NET formation, while miR-125a-3p inhibitor reversed the effect. PET studies revealed that, although the majority of the transplanted exosomes were sequestered in the liver and spleen, a notably high quantity of exosomes was detected in the damaged spinal cord when compared to normal rats. MSC-derived exosomes play a pivotal role in alleviating spinal cord injury, in part through the deactivation of NET formation via miR-125a-3p.
Topics: Rats; Animals; Rats, Sprague-Dawley; Exosomes; Extracellular Traps; Tissue Distribution; Mesenchymal Stem Cells; MicroRNAs; Spinal Cord Injuries; Administration, Intravenous
PubMed: 38397083
DOI: 10.3390/ijms25042406 -
BMJ Medicine 2023To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had...
OBJECTIVE
To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy.
DESIGN
Population based, retrospective cohort study.
SETTING
Ontario, Canada, from 20 December 2021 to 31 August 2022.
PARTICIPANTS
Individuals were included if they were pregnant with an expected date of delivery from 20 December 2021 (start date of third dose eligibility for everyone ≥18 years) to 31 August 2022, who had completed the two doses of primary covid-19 messenger RNA vaccine series before pregnancy, and became eligible for a third dose (≥six months since dose two) before the end of pregnancy.
MAIN OUTCOME MEASURES
Pregnancy outcomes included hypertensive disorders of pregnancy, placental abruption, caesarean delivery, chorioamnionitis, and postpartum hemorrhage. Fetal and neonatal outcomes included stillbirth, preterm birth, admission to neonatal intensive care unit for >24 h, newborn 5 min Apgar score <7, and small-for-gestational age infant (<10th percentile). We estimated hazard ratios and 95% confidence intervals for study outcomes, treating dose three as a time varying exposure and adjusting for confounding using inverse probability weighting.
RESULTS
Among 32 689 births, 18 491 (56.6%) were born to individuals who received a third covid-19 dose during pregnancy. Compared with eligible individuals who did not receive a third dose during pregnancy, no increased risks were associated with receiving a third covid-19 vaccine dose during pregnancy for placental abruption (adjusted hazard ratio 0.84 (95% confidence interval 0.70 to 1.02)), chorioamnionitis (0.67 (0.49 to 0.90)), postpartum haemorrhage (1.01 (0.89 to 1.16)), caesarean delivery (0.90 (0.87 to 0.94)), stillbirth (0.56 (0.39 to 0.81)), preterm birth (0.91 (0.84 to 0.99)), neonatal intensive care unit admission (0.96 (0.90 to 1.03)), 5 min Apgar score<7 (0.96 (0.82 to 1.14)), or small-for-gestational age infant (0.86 (0.79 to 0.93)).
CONCLUSION
Receipt of a third covid-19 vaccine dose during pregnancy was not associated with an increased risk of adverse pregnancy, fetal, or neonatal outcomes. These findings can help to inform evidence based decision making about the risks and benefits of covid-19 booster doses during pregnancy.
PubMed: 37456362
DOI: 10.1136/bmjmed-2023-000632 -
Antibiotics (Basel, Switzerland) Feb 2024Pathogens, such as (. ), have been identified as significant causes of poultry mortality. Poultry can serve as potential sources of . transmission, even when... (Review)
Review
Pathogens, such as (. ), have been identified as significant causes of poultry mortality. Poultry can serve as potential sources of . transmission, even when asymptomatic, posing a substantial threat to food safety and human health. The in ovo administration of antimicrobials is crucial for preventing and/or effectively combating acute and chronic infections caused by poultry pathogens. To achieve this goal, it is critical that antimicrobials are properly injected into embryonic fluids, such as the amnion, to reach target tissues and trigger robust antimicrobial responses. Several protocols based on antimicrobials were evaluated to meet these requirements. This review analyzed the impacts of antimicrobial substances injected in ovo on the control of . in poultry. The reduction in infection rates, resulting from the implementation of in ovo antimicrobials, combined with efforts aimed at hygienic-sanitary action plans in poultry sheds, reinforces confidence that . can be contained before causing large scale damage. For example, antimicrobial peptides and probiotics have shown potential to provide protection to poultry against infections caused by . Issues related to the toxicity and bacterial resistance of many synthetic chemical compounds represent challenges that need to be overcome before the commercial application of in ovo injection protocols focused on microbiological control.
PubMed: 38534640
DOI: 10.3390/antibiotics13030205 -
Reproductive Sciences (Thousand Oaks,... Dec 2023This study compares the effectiveness and safety of oxytocin infusion against oral misoprostol for inducing labour in pregnant women with term prelabor membrane rupture.... (Randomized Controlled Trial)
Randomized Controlled Trial
This study compares the effectiveness and safety of oxytocin infusion against oral misoprostol for inducing labour in pregnant women with term prelabor membrane rupture. We randomized 173 pregnant women presenting with term prelabor rupture of membranes (PROM) at Ain Shams University Maternity Hospital into Group A (underwent induction of labor (IOL) by 25μg misoprostol oral tablet every 4 h, for maximum 5 doses) and an identical Group B: (underwent IOL by oxytocin infusion according to the hospital protocol). Our primary outcome was rate of vaginal delivery within 24 h, while the secondary outcomes included the time till active phase, induction to delivery interval, maternal pyrexia, nausea and vomiting, fetal distress, Apgar score, birth weight, and neonatal intensive care unit admission. Both groups showed high rates of vaginal delivery (82.4% & 87.1% for misoprostol group and oxytocin group respectively) with no significant difference between the two groups (p=0.394). However, patients induced by misoprostol took significantly less time to reach active phase with a shorter induction to delivery interval as compared to patients induced with oxytocin. This difference was clear in multiparous women, but not observed in primiparous women when subgroup analysis was done. No significant difference was found as regards other outcomes. Our study showed that both oral misoprostol and oxytocin are effective and safe for IOL in patients with PROM, with shorter induction-delivery interval in patients induced by oral misoprostol, an effect that is clear in multiparous but not primiparous women. TRIAL REGISTRATION: NCT05215873, on 31/01/2022, "retrospectively registered".
Topics: Infant, Newborn; Female; Pregnancy; Humans; Misoprostol; Oxytocin; Oxytocics; Pregnant Women; Fetal Membranes, Premature Rupture; Labor, Induced
PubMed: 37442883
DOI: 10.1007/s43032-023-01290-0 -
Medicina (Kaunas, Lithuania) Jun 2024The amniotic membrane is widely used in the treatment of chronic wounds, in toxic epidermal necrolysis (TEN), and in the treatment of burns. In our clinical practice,... (Comparative Study)
Comparative Study
The amniotic membrane is widely used in the treatment of chronic wounds, in toxic epidermal necrolysis (TEN), and in the treatment of burns. In our clinical practice, we use amniotic dressings on shallow skin wounds caused by burns. Counteracting infections is an important aspect of working with burn wounds. Therefore, the main goals of this work are to demonstrate the usefulness of amniotic membrane soaked in antiseptics for the prevention of wound infections and to compare the antibacterial efficacy of selected variants of allogeneic and xenogeneic amniotic membrane grafts soaked in specific antiseptic agents. The studied material consisted of human and pig placenta. The human and animal amnions were divided in two parts. The first part consisted of amniotic discs placed on rigid mesh discs and preparing the fresh amnion. The second part of the amnion was frozen at a temperature of -80 °C for 24 h. Then, it was radio-sterilized with a dose of 35 kGy. The amniotic discs were placed on rigid mesh to prepare the radiation-sterilized amnion. The amniotic discs were placed in a 12-well plate and immersed in 3 mL of the appropriate antiseptic solutions: Prontosan, Braunol, Borasol, Microdacyn, Octenilin, Sutrisept, and NaCl as a control. The amniotic discs were incubated in antiseptics for 3 h. The microbiological tests were conducted by placing the antiseptic-infused amniotic discs on microbiological media inoculated with hospital strains. The largest average zone of growth inhibition was observed in dressings soaked with Sutrisept, Braunol, and Prontosan. The greatest inhibition of bacterial growth was achieved for radiation-sterilized porcine amnion impregnated with Braunol and Sutrisept, as well as for radiation-sterilized human amnion impregnated with Braunol. Human and porcine amniotic membrane is effective in carrying antiseptics. Radiation-sterilized amnion seems to inhibit the growth of microorganisms better than fresh amnion.
Topics: Amnion; Humans; Anti-Infective Agents, Local; Burns; Animals; Swine; Female; Transplantation, Homologous; Transplantation, Heterologous
PubMed: 38929632
DOI: 10.3390/medicina60061015 -
International Wound Journal May 2024Allografts derived from live-birth tissue obtained with donor consent have emerged as an important treatment option for wound and soft tissue repairs. Placental membrane...
Allografts derived from live-birth tissue obtained with donor consent have emerged as an important treatment option for wound and soft tissue repairs. Placental membrane derived from the amniotic sac consists of the amnion and chorion, the latter of which contains the trophoblast layer. For ease of cleaning and processing, these layers are often separated with or without re-lamination and the trophoblast layer is typically discarded, both of which can negatively affect the abundance of native biological factors and make the grafts difficult to handle. Thus, a full-thickness placental membrane that includes a fully-intact decellularized trophoblast layer was developed for homologous clinical use as a protective barrier and scaffold in soft tissue repairs. Here, we demonstrate that this full-thickness placental membrane is effectively decellularized while retaining native extracellular matrix (ECM) scaffold and biological factors, including the full trophoblast layer. Following processing, it is porous, biocompatible, supports cell proliferation in vitro, and retains its biomechanical strength and the ability to pass through a cannula without visible evidence of movement or damage. Finally, it was accepted as a natural scaffold in vivo with evidence of host-cell infiltration, angiogenesis, tissue remodelling, and structural layer retention for up to 10 weeks in a murine subcutaneous implant model.
Topics: Humans; Female; Pregnancy; Placenta; Animals; Mice; Tissue Scaffolds; Freeze Drying; Decellularized Extracellular Matrix; Wound Healing
PubMed: 38686514
DOI: 10.1111/iwj.14888 -
BMC Medical Genomics Mar 2024Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not...
BACKGROUND
Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls.
METHODS
Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses.
RESULTS
A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25.
CONCLUSIONS
In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.
Topics: Infant, Newborn; Child; Female; Humans; Child, Preschool; Premature Birth; Extraembryonic Membranes; Obstetric Labor, Premature; Gene Expression Profiling; Transcriptome; Cytokines; Fetal Membranes, Premature Rupture
PubMed: 38443884
DOI: 10.1186/s12920-024-01841-7 -
IScience Nov 2023Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the...
Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as and was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14 AMCs represent activated AMCs at the maternal-fetal interface.
PubMed: 37953944
DOI: 10.1016/j.isci.2023.108118 -
Arquivos Brasileiros de Oftalmologia 2024To evaluate the clinical results of cryopreserved amniotic membrane transplantation as a treatment option for refractory neurotrophic corneal ulcers.
PURPOSE
To evaluate the clinical results of cryopreserved amniotic membrane transplantation as a treatment option for refractory neurotrophic corneal ulcers.
METHODS
This prospective study included 11 eyes of 11 patients who underwent amniotic membrane transplantation for the treatment of refractory neurotrophic corneal ulcers at Hospital de Clínicas da Universidade Federal do Paraná, in the city of Curitiba, from May 2015 to July 2021. Patients underwent different surgical techniques in which the amniotic membrane was applied with the epithelium facing upward to promote corneal re-epithelialization.
RESULTS
The median age of the patients was 60 years (range, 34-82 years), and 64% were men. The predominant etiology of corneal ulcers was herpes zoster (45% of cases). Approximately one-third of the patients (27%) were chronically using hypotensive eye drops, and more than half (54%) had previously undergone penetrating corneal transplantation. At the time of amniotic membrane transplantation, 18% of the eyes had corneal melting, 9% had corneal perforation, and the others had corneal ulceration without other associated complications (73%). The time between clinical diagnosis and surgical treatment ranged from 9 days to 2 years. The corrected visual acuity was worse than 20/400 in 90% of the patients preoperatively, with improvement in 36% after 3 months of the procedure, worsening in 18% and remaining stable in 36%. Of the patients, 81% complained of preoperative pain, and 66% of them reported total symptom relief after the surgical procedure. In one month, 54.6% of the patients presented a closure of epithelial defect, and half of the total group evolved with corneal thinning. The failure rate was 45.5% of the cases.
CONCLUSION
Cryopreserved amniotic membrane transplantation can be considered a good alternative for treating refractory neurotrophic corneal ulcers, as it resulted in significant improvement in pain (66%) and complete epithelial closure (60%) in many patients at 1 month postoperatively. Notably, the high failure rate highlights the need for further studies to identify patientand ulcer-related factors that may influence the outcomes of this procedure.
Topics: Male; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Female; Corneal Ulcer; Ulcer; Amnion; Prospective Studies; Keratitis; Cornea; Pain
PubMed: 38451687
DOI: 10.5935/0004-2749.2023-2022-0341 -
The Journal of Maternal-fetal &... Dec 2023Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical...
BACKGROUND
Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress.
OBJECTIVE
The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful.
METHODS
Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed.
RESULTS
Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B (Patient 15) and (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B from Patient 15. In the gastric fluid sample of Patient 24, were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster ( or ) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (, , and ) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in group than in the other two groups.
CONCLUSION
Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Chorioamnionitis; Ureaplasma; Anti-Bacterial Agents; Infant, Newborn, Diseases; High-Throughput Nucleotide Sequencing; Respiratory Distress Syndrome, Newborn; Amniotic Fluid; Ureaplasma Infections
PubMed: 37150592
DOI: 10.1080/14767058.2023.2207113