Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders

Cellular and Molecular Neurobiology, Год журнала: 2024, Номер 44(1)

Опубликована: Фев. 16, 2024

Abstract HOX transcript antisense intergenic RNA ( HOTAIR ) is a long non-coding (lncRNA) which increasingly being perceived as tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation target gene expression carried out by thorough modulation chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and demethylase lysine-specific 1 (LSD1). Incidentally, was the first lncRNA shown to elicit sponging specific microRNA (miRNA or miR) species in trans-acting manner. It has been extensively studied various cancers, including gliomas regarded prominent pro-tumorigenic pro-oncogenic lncRNA. Indeed, may serve glioma grade predictor prognostic biomarker. The objective this timely review not only outline multifaceted pathogenic roles development but also delineate research findings implicating it critical regulator overall pathophysiology. While major focus on neuro-oncology, wherein represents particularly potent underlying player suitable therapeutic target, mechanisms regulatory actions neurodegeneration, traumatic, hypoxic ischemic injuries, neuropsychiatric disorders are presented. Graphical HOTAIR-mediated epigenetic DNA miRNAs. 5′ end regulates H3K27 trimethylation activity catalytic subunit enhancer Zeste homolog (EZH2) (PRC2), its 3′ modulates H3K4 demethylation binds competitively inhibits functions miRNAs, altering downstream genes.

Язык: Английский

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Acupuncture Extended the Thrombolysis Window by Suppressing Blood–Brain Barrier Disruption and Regulating Autophagy–Apoptosis Balance after Ischemic Stroke

Brain Sciences, Год журнала: 2024, Номер 14(4), С. 399 - 399

Опубликована: Апрель 19, 2024

Background: Ischemic stroke (IS) is one of the leading causes death and disability worldwide. The narrow therapeutic window (within 4.5 h) severe hemorrhagic potential limits efficacy recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) acupuncture an integral part traditional Chinese medicine, specifically designed to address acute ischemic by targeting key acupoints such as Shuigou (GV26) Neiguan (PC6). In this study, we explored XNKQ in extending time interrogated molecular mechanisms responsible effect. Methods: effect was evaluated via TTC staining, neuronal score evaluation, transformation assay, H&E staining. RNA sequencing (RNA-seq) technology performed identify targets intervention acupuncture. Evans blue staining transmission electron microscopy were used assess blood–brain barrier (BBB) integrity. Immunofluorescence co-immunoprecipitation evaluate level autophagy apoptosis validate their interactions with BBB endothelial cells. Results: Acupuncture alleviated infarction neurological deficits extended 6 h. RNA-seq revealed 16 predictors intervention, which related suppressing inflammation restoring function blood vessels. Furthermore, suppressed leakage preserved tight junction protein expression. protective associated regulation autophagy–apoptosis balance dissociated Beclin1/Bcl-2 complex, thereby promoting reducing apoptosis. Conclusion: could serve adjunctive therapy rt-PA thrombolysis, aiming extend mitigate ischemia–reperfusion injury. disruption regulating balance, turn IS. These findings provide a rationale further exploration complementary candidate co-administered rt-PA.

Язык: Английский

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Targeting blood-brain barrier for sepsis-associated encephalopathy: Regulation of immune cells and ncRNAs

Brain Research Bulletin, Год журнала: 2024, Номер 209, С. 110922 - 110922

Опубликована: Март 6, 2024

Sepsis causes significant morbidity and mortality worldwide, most surviving patients show acute or chronic mental disorders, which are known as sepsis-associated encephalopathy (SAE). SAE involves many pathological processes, including the blood-brain barrier (BBB) damage. The BBB is located at interface between central nervous system surrounding environment, protects (CNS) from invasion of exogenous molecules, harmful substances microorganisms in blood. Recently, a growing number studies have indicated that destruction was involved played an important role SAE-induced brain injury. In present review, we firstly reveal processes such neurotransmitter oxidative stress, immune dysfunction destruction. Moreover, introduce structure BBB, describe cells microglia astrocytes participate after SAE. Furthermore, view current research on non-coding RNAs (ncRNAs), explain regulatory mechanism ncRNAs long noncoding (lncRNAs), microRNAs (miRNAs) circular (circRNAs) Finally, propose some challenges perspectives regulating functions Hence, basis these effects, both may be developed therapeutic targets to protect for patients.

Язык: Английский

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Advancements in strategies for overcoming the blood–brain barrier to deliver brain-targeted drugs

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16

Опубликована: Авг. 26, 2024

The blood-brain barrier is known to consist of a variety cells and complex inter-cellular junctions that protect the vulnerable brain from neurotoxic compounds; however, it also complicates pharmacological treatment central nervous system disorders as most drugs are unable penetrate on basis their own structural properties. This dramatically diminished therapeutic effect drug compromised its biosafety. In response, number often delivered lesions in invasive ways bypass obstruction barrier, such subdural administration, intrathecal convection-enhanced delivery. Nevertheless, these intrusive strategies introduce risk injury, limiting clinical application. recent years, intensive development nanomaterials science interdisciplinary convergence medical engineering have brought light penetration for brain-targeted drugs. this paper, we extensively discuss limitations delivery non-invasive nanomedicine disruption. meantime, analyze strengths provide outlooks further systems.

Язык: Английский

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The Application of MicroRNAs in Traumatic Brain Injury: Mechanism Elucidation and Clinical Translation

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Язык: Английский

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Identification of pivotal genes and regulatory networks associated with SAH based on multi-omics analysis and machine learning

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 24, 2025

Subarachnoid hemorrhage (SAH) is a disease with high mortality and morbidity, its pathophysiology complex but poorly understood. To investigate the potential therapeutic targets post-SAH, SAH-related feature genes were screened by combined analysis of transcriptomics metabolomics rat cortical tissues following SAH proteomics cerebrospinal fluid from patients, as well WGCNA machine learning. The competitive endogenous RNAs (ceRNAs) transcription factors (TFs) regulatory networks constructed further validated molecular biology experiments. A total 1336 differentially expressed proteins identified, including 729 downregulated 607 upregulated. immune microenvironment changed after changement persisted at 7d. Through multi-omics bioinformatics techniques, five (A2M, GFAP, GLIPR2, GPNMB, LCN2) closely related to microenvironment. In addition, ceRNAs TFs constructed. increased expression levels A2M GLIPR2 verified, co-localization intravascular microthrombus was demonstrated. Multiomics tools used predict associated confirmed through network development. These molecules might play key role in may serve biological markers provide clues for exploring options.

Язык: Английский

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Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application

Genes, Год журнала: 2024, Номер 15(4), С. 431 - 431

Опубликована: Март 29, 2024

Many investigations have evaluated the expression of noncoding RNAs (ncRNAs) as well their related molecular functions and biological machineries in individuals with alcohol dependence. Alcohol dependence may be one most prevailing psychological disorders globally, its pathogenesis is intricate inadequately comprehended. There substantial evidence indicating significant links between multiple genetic factors development In particular, critical roles ncRNAs been emphasized pathology mental illnesses, probably including comprehension action modification, furthermore, they emerged therapeutic targets for a variety psychiatric It worth mentioning that dysregulated has regularly detected An in-depth knowledge m6A modification valuable novel treatment against general, more profound understanding practical might make important contributions to precise diagnosis and/or actual management Here, this review, we mostly focused on up-to-date regarding alterations modifications Then, present prospects future research applications concept engram system.

Язык: Английский

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The multifaceted functions of long non-coding RNA HOTAIR in neuropathologies and its potential as a prognostic marker and therapeutic biotarget

Expert Reviews in Molecular Medicine, Год журнала: 2024, Номер 26

Опубликована: Янв. 1, 2024

Abstract Long non-coding RNAs (lncRNAs) are progressively being perceived as prominent molecular agents controlling multiple aspects of neuronal (patho)physiology. Amongst these is the HOX transcript antisense intergenic RNA, often abbreviated HOTAIR . epigenetically regulates its target genes via interaction with two different chromatin-modifying agents; histone methyltransferase polycomb-repressive complex 2 and demethylase lysine-specific 1. Parenthetically, elicits trans-acting sponging function against micro-RNA species. Oncological research studies have confirmed pathogenic functions in cancer types, such gliomas proposed it a pro-oncological lncRNA. In fact, expression has been suggested to be predictor severity/grade gliomas, prognostic biomarker. Moreover, propound influence other brain heath disease states just beginning unravelled. The objective this review recapitulate all relevant data pertaining regulatory roles To end, we discuss mechanisms diseases, neurodegeneration, traumatic injury neuropsychiatric disorders. Finally, also summarize results from incriminating pathogeneses cancers. Implications serving suitable therapeutic neuropathologies discussed.

Язык: Английский

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Fucoxanthin ameliorates traumatic brain injury by suppressing the blood–brain barrier disruption

iScience, Год журнала: 2023, Номер 26(11), С. 108270 - 108270

Опубликована: Окт. 20, 2023

Fucoxanthin is the most abundant marine carotenoid extracted from seaweed. Our previous study has shown that fucoxanthin inhibited oxidative stress after traumatic brain injury (TBI). However, effects of on TBI-induced blood-brain barrier (BBB) destruction have not been well understood. In present study, we found improved neurological dysfunction, reduced edema, attenuated cortical lesion volume, and decreased dendrites loss TBI in vivo. Moreover, suppressed BBB leakage, preserved tight junction (TJ) adherens (AJ) proteins, MMP-9 expression. Furthermore, alleviated apoptosis ferroptosis, activated mitophagy endothelial cells (ECs) TBI. protection was when inhibited. Importantly, also provided protective bEnd.3 Taken together, our results suggested played a key role through mitophagy.

Язык: Английский

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Gut Microbiota and Non-coding RNAs Might Be Involved in the Pathogenesis of Alcohol Dependence

Опубликована: Фев. 27, 2024

A great deal of studies have assessed the expression noncoding RNAs (ncRNAs) as well their relevant molecular functions and biological mechanisms in individuals alcohol dependence. Alcohol dependence is one most prevalent neuropsychological disorders worldwide, its pathogenesis intricate inadequately understood. There considerable evidence demonstrating substantial links between multiple genetic factors development Critical roles ncRNAs been emphasized pathophysiology mental diseases including In comprehension action modification, they emerged therapeutic targets for a variety psychiatric illness Worth mentioning, dysregulated has regularly detected An in-depth knowledge m6A modification may be valuable novel treatment against general, deeper functional make significant contributions to precise diagnosis and/or actual Here this review, we mostly focused on up-to-date regarding alterations modifications dependence, then, presented prospects future research application with concept engram-system.

Язык: Английский

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