Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain

Ozen, Maide; Kitase, Yuma; Vasan, Vikram; Burkhardt, Christopher; Ramachandra, Sindhu; Robinson, Shenandoah; Jantzie, Lauren L.

doi:10.3390/ijms22115773

Cited by 5 publications

(2 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be mentioned that, after HMOX1 induction, iron is also released [93]. Especially in the brain, excessive iron levels can be toxic due to its pro-oxidant capacity (as example [5,6,44,[94][95][96]). On the contrary, HMOX1, iron, cellular redox status, and inflammation regulate the increased vulnerability to ferroptosis in glioblastoma, the most recurrent brain tumor [97][98][99][100][101][102][103].…”

Section: Gsk3bmentioning

confidence: 99%

Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases

Jayanti,

Vitek,

Verde

et al. 2024

Biomolecules

View full text Add to dashboard Cite

The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the “yellow players—YP”) are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.

show abstract

Section: Gsk3bmentioning

confidence: 99%

Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases

Jayanti,

Vitek,

Verde

et al. 2024

Biomolecules

View full text Add to dashboard Cite

show abstract

“…It is well recognized that significant inflammatory, infectious, or physiologically stressful events during late gestation or the perinatal period are contributing factors in the genesis of CP [9] [10]. Acute inflammation, pre-term birth, and maternal infection are also associated with alterations to the methylome [11], and it has been proposed that the onset of CP may be associated with alterations in DNA methylation patterns [8].…”

Section: Introductionmentioning

confidence: 99%

Novel Machine Learning Analysis Algorithm ofDNA Methylation Patterns Identifies CerebralPalsy with Concurrent Epilepsy

Hicks,

Robinson,

Lee

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Spastic cerebral palsy, the most common pediatric-onset disabling condition with an estimated prevalence of 0.2% in children, is a complex condition characterized by stiff movement, muscle contractures, and abnormal gait that can diminish quality of life. Spastic CP accounts for approximately 83% of all CP cases and frequently co-occurs with other complex conditions, like epilepsy. An estimated 42% of spastic CP cases have co-occurring epilepsy. Unfortunately, CP is often difficult to diagnose. Although most children with CP are born with it or acquire it immediately after birth, many are not identified until after 19 months of age with CP diagnosis often not confirmed until 5 years of age. New bioinformatic approaches to identify CP earlier are needed. Recent studies indicate that altered DNA methylation patterns associated with CP may have diagnostic value. The potential confounding effects of co-occurrent epilepsy on these patterns are not known. We evaluated machine learning classification of CP patients with or without co-occurring epilepsy. Results Whole blood samples were collected from 30 study participants diagnosed with epilepsy (n=4), spastic CP (n=10), both (n=8), or neither (n=8). A novel Support-Vector-Machine learning algorithm was developed to identify methylation loci that have ability to classify CP from controls in the presence or absence of epilepsy. This algorithm was also employed to measure classification ability of identified methylation loci. After preprocessing of data, isolation of important methylation loci was performed in a binary comparison between CP and controls, as well as in a 4-way scheme, encapsulating epilepsy diagnoses. The classification ability was similarly assessed. CP Classification performance wasevaluated with and without inclusion of epilepsy as a feature. Median F1 scoreswere 0.67 in 4-class comparison, and 1.0 in the binary classification, outperforming Linear-Discriminant-Analysis (0.57 and 0.86, respectively). Conclusion This novel algorithm was able to classify study participants with spastic CPand/or epilepsy from controls with significant performance. The algorithm shows promise for rapid identification in methylation data of diagnostic methylation loci. In this model, Support Vector Machines outperformed Linear Discriminant Analysis in classification. In the evaluation of epigenetics-based diagnostics for CP, epilepsy may not be a significant confounding factor.

show abstract

Blocking P2RX7 Attenuates Ferroptosis in Endothelium and Reduces HG-induced Hemorrhagic Transformation After MCAO by Inhibiting ERK1/2 and P53 Signaling Pathways

et al. 2022

View full text Add to dashboard Cite

BackgroundHyperglycemia is a risk factor for poor prognosis after acute ischemic stroke and promote the occurrence of hemorrhagic transformation (HT). The activation of P2RX7 play an important role in endotheliocyte damage and BBB disruption. Ferroptosis is a novel pattern of programmed cell death caused by the accumulation of intracellular iron and lipid peroxidation, resulting in ROS production and cell death. This study is to explore the mechanism of P2RX7 could reduce HT pathogenesis after acute ischemic stroke through regulating endotheliocyte ferroptosis. MethodsMale SD rats were performed to establish middle cerebral artery occlusion (MCAO) model injected with 50% high glucose (HG) and HUVECs were subjected to OGD/R treated with high glucose (30mM) for establishing HT model in vivo and in vitro. P2RX7 inhibitor (BBG) and P2RX7 small interfering RNAs (siRNA) were used to investigate the role of P2RX7 in BBB after MCAO in vivo and OGD/R in vitro, respectively. The neurological de cits, infarct volume, degree of intracranial hemorrhage, integrity of the BBB, immunoblotting and immuno uorescence were evaluated both 24 h after MCAO. ResultsOur study found that the level of P2RX7 was gradually increased after MCAO and/or treated with HG. Our results showed that treatment with HG after MCAO can aggravate neurological de cits, infarct volume, oxidative stress, iron accumulation and integrity of the BBB in HT model, and HG-induced HUVECs damage. The inhibition of P2RX7 reversed the damage effect of HG, signi cantly downregulated the expression level of P53, HO-1 and p-ERK1/2 and upregulated the level of SLC7A11 and GPX4, which implicated that P2RX7 inhibition attenuated oxidative stress and ferroptosis of endothelium in vivo and in vitro. ConclusionOur data provide evidence that the P2RX7 play an important role in HG-associated oxidative stress, endothelial damage and BBB disruption, which regulates HG-induced HT by ERK1/2 and P53 signaling pathways after MCAO.

show abstract

Chorioamnionitis Precipitates Perinatal Alterations of Heme-Oxygenase-1 (HO-1) Homeostasis in the Developing Rat Brain

Cited by 5 publications

References 46 publications

Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases

Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases

Novel Machine Learning Analysis Algorithm ofDNA Methylation Patterns Identifies CerebralPalsy with Concurrent Epilepsy

Blocking P2RX7 Attenuates Ferroptosis in Endothelium and Reduces HG-induced Hemorrhagic Transformation After MCAO by Inhibiting ERK1/2 and P53 Signaling Pathways

Contact Info

Product

Resources

About