Methyl Donors, Epigenetic Alterations, and Brain Health: Understanding the Connection

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2346 - 2346

Опубликована: Янв. 25, 2023

Methyl donors such as choline, betaine, folic acid, methionine, and vitamins B6 B12 are critical players in the one-carbon metabolism have neuroprotective functions. The comprises a series of interconnected chemical pathways that important for normal cellular Among these those methionine folate cycles, which contribute to formation S-adenosylmethionine (SAM). SAM is universal methyl donor methylation reactions histone DNA methylation, two epigenetic mechanisms regulate gene expression play roles human health disease. Epigenetic been considered bridge between effects environmental factors, nutrition, phenotype. Studies animal models indicated importance optimal levels on brain behavior across lifespan. Imbalances micronutrients during periods development linked alterations genes function. We present studies support link imbalances donors, alterations, stress-related disorders. Appropriate should then be monitored at all stages healthier brain.

Язык: Английский

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LncRNA‐MEG3 Mediated Diabetic Cerebral Ischemia–Reperfusion Injury‐Induced Apoptosis via Modulating Interaction Between Annexin A2 and Akt in Mitochondria

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background In clinical domains, encompassing neurosurgery and macrovascular cardiac procedures, certain interventions result in cerebral ischemia‐ reperfusion injury (CIRI). Diabetes mellitus (DM) increases the risk of CIRI worsens severity neurological impairment. It was documented that lncRNA‐MEG3 contributed to pathogenesis CIRI. However, pivotal significance diabetic has never been studied. Aims This study's aims were two‐fold, (1) figure out influence on dysfunction subsequent ischemic injury, (2) elucidate its potential role mitochondria‐related apoptosis via modulating Anxa2 signaling pathway. Materials Methods We mainly collected plasma from patients measure expression lncRNA‐MEG3, explored molecular mechanism combined with DM by immunofluorescence, western blot, co‐ip other biology experiments rat MACO+DM model cellular OGD/R+HG model. Results LncRNA‐MEG3 DM+AIS cases remarkably higher than AIS healthy controls. Moreover, strongly linked National Institutes Health Stroke Scale (NIHSS) score. Additionally, findings unveiled depletion alleviated impairments following rats, death resulted Oxygen‐glucose deprivation (OGD) plus hyperglycemic brain microvascular endothelial cells (RBMVECs) concomitant increased phosphorylation Annexin A2 (Anxa2) at Tyr23. Meanwhile, over Anxa2, identified as a lncRNA‐MEG3‐associated mitochondrial protein, suppressed mitochondria‐derived apoptosis. Importantly, knockdown enhanced translocation promoting Tyr23 OGD+HG‐treated RBMVECs. Furthermore, Akt Ser473 bound mitochondria, which involved depletion‐induced neuroprotection. mobilized mitochondria Plectin‐dependent manner subsequently impeded interaction between p‐Anxa2 p‐Akt. Discussion Conclusion The outcomes provided evidence appeared an unfavorable prognostic factor for revealed could be protective against CIRI‐induced through binding mitochondria.

Язык: Английский

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Transcriptome Analysis of Non-coding RNAs and mRNAs in the Dorsal Root Ganglion of Peripheral Nerve Injury-Induced Neuropathic Pain

Biochemical Genetics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Язык: Английский

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Functional Interactions Between lncRNAs/circRNAs and miRNAs: Insights Into Rheumatoid Arthritis

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Фев. 7, 2022

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that affect synovitis, bone, cartilage, and joint. RA leads to bone cartilage damage extra-articular disorders. However, pathogenesis still unclear, lack effective early diagnosis treatment causes severe disability, ultimately, death. Accumulating evidence revealed regulatory network includes long non-coding RNAs (lncRNAs)/circular (circRNAs), micro (miRNAs), messenger (mRNA) plays important roles in regulating pathological physiological processes RA. lncRNAs/circRNAs act as miRNA sponge competitively bind regulate expression mRNA synovial tissue, FLS, PBMC, participate regulation proliferation, apoptosis, invasion, inflammatory response. Thereby providing new strategies for its treatment. In this review, we comprehensively summarized mechanisms lncRNA/circRNA-miRNA-mRNA potential biomarkers therapeutic targets

Язык: Английский

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The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

Biomolecules, Год журнала: 2023, Номер 13(3), С. 571 - 571

Опубликована: Март 21, 2023

Stroke causes varying degrees of neurological deficits, leading to corresponding dysfunctions. There are different therapeutic principles for each stage pathological development. Neuroprotection is the main treatment in acute phase, and functional recovery becomes primary subacute chronic phases. Neuroplasticity considered basis restoration rehabilitation after stroke, including remodeling dendrites dendritic spines, axonal sprouting, myelin regeneration, synapse shaping, neurogenesis. Spatiotemporal development affects spontaneous rewiring neural circuits brain networks. Microglia resident immune cells that contribute homeostasis under physiological conditions. activated immediately phenotypic polarization changes phagocytic function crucial regulating focal global inflammation recovery. We have previously shown neuroplasticity spatiotemporally consistent with microglial activation, suggesting microglia may a profound impact on stroke be key target post-stroke rehabilitation. In this review, we explore as well functions mechanisms polarization, phagocytosis. This followed by summary microglia-targeted rehabilitative interventions influence promote

Язык: Английский

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CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability

Molecular Therapy — Nucleic Acids, Год журнала: 2022, Номер 31, С. 57 - 67

Опубликована: Дек. 5, 2022

Transient focal ischemia decreased microRNA-7 (miR-7) levels, leading to derepression of its major target α-synuclein (α-Syn) that promotes secondary brain damage. Circular RNA CDR1as is known regulate miR-7 abundance and function. Hence, we currently evaluated functional significance after ischemia. middle cerebral artery occlusion (MCAO) in adult mice significantly downregulated both levels the peri-infarct cortex between 3 72 h reperfusion. Interestingly, neither pri-miR-7a nor 7b was altered ischemic brain. Intracerebral injection an AAV9 vector containing a gene increased by 21 days persisted up 4 months without inducing any observable toxicity sham MCAO groups. Following transient MCAO, there significant increase binding Ago2/miR-7 AAV9-CDR1as cohort compared with AAV9-Control at 1 day overexpression suppressed post-stroke α-Syn protein induction, promoted motor function recovery, infarct size, curtailed markers apoptosis, autophagy mitochondrial fragmentation, inflammation AAV9-Control-treated cohort. Overall, our findings imply reconstitution neuroprotective stroke, probably protecting preventing α-Syn-mediated neuronal death.

Язык: Английский

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Novel long non-coding RNAs associated with inflammation and macrophage activation in human

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Март 10, 2023

Abstract Inflammation plays a central role in immune response and macrophage activation. Emerging studies demonstrate that along with proteins genomic factors, noncoding RNA are potentially involved regulation of inflammation. Our recent study demonstrated lncRNA HOTAIR key roles cytokine expression inflammation macrophages. The primary goal this is to discover novel lncRNAs crucial players inflammation, activation, humans. Towards this, we have stimulated THP1-derived macrophages (THP1-MΦ) lipopolysaccharides (LPS) performed the whole transcriptome RNA-seq analysis. Based on analysis, discovered well-known marker for (such as cytokines), series long RNAs (lncRNAs) were highly induced upon LPS-stimulation macrophages, suggesting their potential We termed these family Long-noncoding Associated (LinfRNA). Dose time dependent analysis many human LinfRNA (hLinfRNAs) expressions follow similar patterns expressions. Inhibition NF-κB suppressed most hLinfRNAs via activation during Antisense-mediated knockdown hLinfRNA1 LPS-induced cytokines pro-inflammatory genes such IL6, IL1β, TNFα expression, functionality Overall, regulators may be linked inflammatory metabolic diseases.

Язык: Английский

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Bipolar disorder-iPSC derived neural progenitor cells exhibit dysregulation of store-operated Ca2+ entry and accelerated differentiation

Molecular Psychiatry, Год журнала: 2023, Номер 28(12), С. 5237 - 5250

Опубликована: Июль 4, 2023

Abstract While most of the efforts to uncover mechanisms contributing bipolar disorder (BD) focused on phenotypes at mature neuron stage, little research has considered events that may occur during earlier timepoints neurodevelopment. Further, although aberrant calcium (Ca 2+ ) signaling been implicated in etiology this condition, possible contribution store-operated Ca entry (SOCE) is not well understood. Here, we report and developmental dysregulations related SOCE BD patient induced pluripotent stem cell (iPSC)-derived neural progenitor cells (BD-NPCs) cortical-like glutamatergic neurons. First, using a re-addition assay found BD-NPCs neurons had attenuated SOCE. Intrigued by finding, then performed RNA-sequencing uncovered unique transcriptome profile suggesting accelerated neurodifferentiation. Consistent with these results, measured slower rate proliferation, increased neurite outgrowth, decreased size neurosphere formations BD-NPCs. Also, observed subventricular areas developing cerebral organoids. Finally, NPCs demonstrated high expression let-7 family while miR-34a, both being microRNAs previously neurodevelopmental deviations etiology. In summary, present evidence supporting an transition towards neuronal stage be indicative early pathophysiological features disorder.

Язык: Английский

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Identification of brain endothelial cell-specific genes and pathways in ischemic stroke by integrated bioinformatical analysis

Brain Circulation, Год журнала: 2023, Номер 9(4), С. 228 - 239

Опубликована: Окт. 1, 2023

Ischemic stroke (IS) is a life-threatening condition with limited treatment options; thus, finding the potential key genes for novel therapeutic targets urgently needed. This study aimed to explore candidate and pathways of brain microvessel endothelial cells (ECs) in IS by bioinformatics analysis.

Язык: Английский

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Critical roles of non-coding RNAs in lifecycle and biology of Marek’s disease herpesvirus

Science China Life Sciences, Год журнала: 2023, Номер 66(2), С. 251 - 268

Опубликована: Янв. 5, 2023

Язык: Английский

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