Viable bacterial colonization is highly limited in the human intestine in utero

Nature Medicine, Год журнала: 2020, Номер 26(4), С. 599 - 607

Опубликована: Фев. 24, 2020

Язык: Английский

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Epigenetic responses and the developmental origins of health and disease

Journal of Endocrinology, Год журнала: 2019, Номер 242(1), С. T105 - T119

Опубликована: Май 29, 2019

Maternal and paternal factors influence offspring development program its genome for successful postnatal life. Based on the stressors during gestation, pregnant female prepares fetus outside environment. This preparation is achieved by changing epigenome of referred to as 'developmental programming'. For instance, nutritional insufficiency in utero will lead programming events that prepare cope up with nutrient scarcity following birth; however, may not face birth. discrepancy between predicted exposed environments are perceived 'stress' result cardiovascular metabolic disorders. Thus, this developmental be both beneficial well harmful depending prenatal vs Over past three decades, accumulating evidence supports hypothesis Developmental Origin Health Disease (DOHaD) fetal phenotype without altering genotype per se. These heritable modifications gene expression occur through DNA methylation, histone modification noncoding RNA-associated activation or silencing, all defined epigenetic modifications. In present review, we summarize supporting regulation a significant component DOHaD.

Язык: Английский

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HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury

Cellular & Molecular Biology Letters, Год журнала: 2021, Номер 26(1)

Опубликована: Сен. 3, 2021

Abstract Background Endothelial cell (EC) injury accelerates the progression of diabetic macrovascular complications. Hypoxia is an important cause EC injury. Hypoxia-inducible factor-1 alpha (HIF-1α) hypoxia regulatory protein. Our previous studies showed that high-glucose and hypoxic conditions could upregulate HIF-1α expression enhance inflammatory injury, independently nuclear factor kappa-B (NF-κB) pathway. However, it not clear whether plays a role in vascular disease through epigenetic-related mechanisms. Methods We conducted gene analysis molecular mechanistic human umbilical vein endothelial cells (HUVECs) induced by hyperglycemia using RNA sequencing (RNA-seq) small interfering (si-HIF-1α). determined Jumonji domain-containing protein 1 A (JMJD1A) quantitative reverse transcription-polymerase chain reaction (qRT-PCR) Western blot, analyzed secretion supernatant enzymelinked immunosorbent assay (ELISA), assessed interaction between JMJD1A chromatin immunoprecipitation (Ch-IP). used Cell Counting Kit8 (CCK-8) to analyze viability, oxidative stress indicators detection kit flow cytometry. Results High glucose up-regulated expression, down-regulated decreased level inflammation HUVECs. To determine downstream pathways, we observed histone demethylases genes related pathway RNA-sEq. Among these, was most upregulated demethylases. Moreover, bound promoter JMJD1A, ameliorative effects si-HIF-1α on cytokines hypoxia-induced HUVECs were reversed overexpression. Furthermore, knockdown JMJD1A-related factors, JMJD1A-knockdown downregulation enriched FOS FOSB might be protective transcription factors. Conclusions These findings provide novel evidence HIF-1α/JMJD1A signaling involved high hypoxia. Also, this act as regulator inflammatory-related events response thus contribute pathological diabetes disease.

Язык: Английский

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“The First Thousand Days” Define a Fetal/Neonatal Neurology Program

Frontiers in Pediatrics, Год журнала: 2021, Номер 9

Опубликована: Авг. 2, 2021

Gene–environment interactions begin at conception to influence maternal/placental/fetal triads, neonates, and children with short- long-term effects on brain development. Life-long developmental neuroplasticity more likely results during critical/sensitive periods of maturation over these first 1,000 days. A fetal/neonatal program (FNNP) applying this perspective better identifies trimester-specific mechanisms affecting the (MPF) triad, expressed as malformations destructive lesions. Maladaptive MPF triad impair progenitor neuronal/glial populations within transient embryonic/fetal structures by processes such maternal immune activation. Destructive fetal lesions later in pregnancy result from ischemic placental syndromes associated great obstetrical syndromes. Trimester-specific diseases may negatively impact labor delivery outcomes. Neonatal neurocritical care addresses symptomatic minority who express neonatal neurological syndromes: encephalopathy, seizures, stroke, encephalopathy prematurity. The asymptomatic majority present neurologic disorders before 2 years age without prior detection. principle ontogenetic adaptation helps guide diagnostic process days identify phenotypes using systems-biology analyses. This strategy will foster innovative interdisciplinary diagnostic/therapeutic pathways, educational curricula, research agenda among multiple FNNP. Effective early-life programs help reduce disease burden across lifespan successive generations.

Язык: Английский

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Pathophysiology of Perinatal Asphyxia in Humans and Animal Models

Biomedicines, Год журнала: 2022, Номер 10(2), С. 347 - 347

Опубликована: Фев. 1, 2022

Perinatal asphyxia is caused by lack of oxygen delivery (hypoxia) to end organs due an hypoxemic or ischemic insult occurring in temporal proximity labor (peripartum) (intrapartum). Hypoxic-ischemic encephalopathy the clinical manifestation hypoxic injury brain and usually graded as mild, moderate, severe. The search for useful biomarkers precisely predict severity lesions perinatal hypoxic-ischemic (HIE) a field increasing interest. As pathophysiology not fully comprehended, gold standard treatment remains active area research. Hypothermia has proven be effective neuroprotective strategy been implemented routine. Current studies are exploring various add-on therapies, including erythropoietin, xenon, topiramate, melatonin, stem cells. This review aims perform updated integration pathophysiological processes after humans animal models allow us answer some questions provide interim update on progress this field.

Язык: Английский

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A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 10, 2024

Abstract High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues well phenotypic 20 bio-indicators. characterize transcriptional changes of all genes each tissue, examine multi-tissue temporal dynamics interactions among genes. Particularly, identify critical functional regulating short response to tissue (e.g., PARG cerebellum HMOX1 colon). further TAD-constrained cis -regulatory elements, which suppress activity most under hypoxia. Phenotypic evidence indicate that antenatal could improve tolerance offspring. Furthermore, provide time-series expression candidate associated with human mountain sickness BMPR2 ) high-altitude adaptation HIF1A ). Our study provides valuable resources insights future hypoxia-related studies mammals.

Язык: Английский

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Effects of hypoxia on the heart of the juvenile four-finger threadfin (Eleutheronema tetradactylum) based on physiological indicators and transcriptome analysis

Frontiers in Marine Science, Год журнала: 2025, Номер 12

Опубликована: Фев. 5, 2025

This study evaluated the effects of hypoxia on heart juvenile four-finger threadfin ( Eleutheronema tetradactylum ) through physiological and transcriptome analysis. Juveniles with an average weight 122.82 g length 24.60 cm were used. Hypoxia significantly increased serum myocardial enzyme activities, including creatine kinase (CK), kinase-MB isoenzyme, lactate dehydrogenase (LDH), α-hydroxybutyrate (HDBH). These indicators initially rose then declined, reflecting cardiac stress suggesting their potential as early biomarkers for real-time aquaculture monitoring. Histological analysis revealed structural damage in fibers under hypoxia, increasing severity over time. underscores need to minimize oxygen fluctuations prevent tissue degeneration. Transcriptome identified upregulated genes involved cell communication, immune responses, intracellular signaling, offering targets breeding hypoxia-tolerant species. Kyoto Encyclopedia Genes Genomes pathway enrichment highlighted key pathways such mitogen-activated protein (MAPK), hypoxia-inducible factor-1 (HIF-1), endocytosis, phagosome formation. The MAPK plays a critical role cellular survival, proliferation, apoptosis. Hypoxia-induced activation MAPKs like ERK, JNK, p38 regulates stress-responsive genes. HIF-1 signaling homeostasis, HIF-1α stabilizing hypoxia-responsive VEGFA, which promotes vascular remodeling enhances delivery. findings collectively offer practical applications enhancing management, monitoring biochemical markers, adopting breeding, adjusting environmental conditions mitigate stress, ensuring better productivity sustainability. research provides foundation further studies molecular mechanisms

Язык: Английский

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Intervention against hypertension in the next generation programmed by developmental hypoxia

PLoS Biology, Год журнала: 2019, Номер 17(1), С. e2006552 - e2006552

Опубликована: Янв. 22, 2019

Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy increased cardiovascular disease in the adult offspring. However, translational isolating mechanisms to design intervention are lacking. Sheep humans share similar precocial developmental milestones anatomy physiology. We tested hypothesis sheep that maternal treatment with antioxidants protects against fetal growth restriction programmed hypertension adulthood gestation complicated by chronic hypoxia, most common consequence pregnancy. Using bespoke isobaric chambers, chronically catheterized carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C (maternal 200 mg.kg−1 IV daily) for last third of gestation. In one cohort, arterial blood gas status, value at which 50% hemoglobin is saturated (P50), nitric oxide (NO) bioavailability, oxidative stress, antioxidant capacity were determined. another, naturally delivered offspring raised under until early (9 months). Lambs instrumented function vivo. Following euthanasia, femoral segments isolated endothelial determined wire myography. Hypoxic induced stress. At adulthood, it enhancing vasoconstrictor reactivity impairing NO-independent function. Maternal hypoxic improved transplacental oxygenation enhanced while increasing NO offsetting constrictor hyper-reactivity replenishing These discoveries provide novel insight into interventions adult-onset an model species temporal humans.

Язык: Английский

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Evidence for altered energy metabolism, increased lactate, and decreased pH in schizophrenia brain: A focused review and meta-analysis of human postmortem and magnetic resonance spectroscopy studies

Schizophrenia Research, Год журнала: 2020, Номер 223, С. 29 - 42

Опубликована: Сен. 1, 2020

Язык: Английский

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Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System

Frontiers in Pediatrics, Год журнала: 2020, Номер 8

Опубликована: Фев. 26, 2020

Perinatal asphyxia (PA) is a burdening pathology with high short-term mortality and severe long-term consequences. Its incidence, reaching as 10 cases per 1000 live births in the less developed countries, prompts need for better awareness prevention of at risk, together management by easily applicable protocols. PA acts first foremost on nervous tissue, but also heart, hypoxia subsequent ischemia-reperfusion injury. Myocardial development birth still incomplete cannot adequately respond to this aggression. Cardiac dysfunction, including low ventricular output, bradycardia, pulmonary hypertension, complicates already compromised circulatory status newborn PA. Multiorgan especially cardiovascular failure seem play crucial role secondary phase hypoxic-ischemic encephalopathy (HIE) its rate. Hypothermia an acceptable solution HIE, there fragile equilibrium between therapeutic gain instability. A profound understanding underlying mechanisms systems close collaboration bench bedside specialists these domains compulsory. More resources be directed toward consecutive decrease dysfunction. Not much can done case unexpected acute event that produces PA, where recognition prompt delivery are key factors positive clinical result. However, situation different high-risk pregnancies or circumstances make fetus more vulnerable asphyxia. Improving outcome possible through careful monitoring, identifying pregnancies, implementation novel prenatal strategies. Also, apart from supporting heart episode, protocols follow-up. This will increase our any lasting myocardial damage enhance perspective real impact The goal article review data consequences context immature system, discuss potential contribution impairment short outcomes, propose further directions research field.

Язык: Английский

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