Comparative Analysis of Circular RNAs Expression and Function between Aortic and Intracranial Aneurysms.

An aneurysm is an abnormal enlargement or bulging of the wall of a blood vessel. Most often, aneurysms occur in large blood vessels - the aorta (Thoracic Aortic Aneurysm (TAA) and Abdominal Aortic Aneurysm (AAA) and brain vessels (Intracranial Aneurysm (IA)). Despite the presence of significant differences in the pathogenesis of the development and progression of IA and TAA/AAA, there are also similarities. For instance, both have been shown to be strongly influenced by shear stress, inflammatory processes, and enzymatic destruction of the elastic lamellae and extracellular matrix (ECM) proteins of the vascular wall. Moreover, although IA and TAA are predominantly considered arteriopathies with different pathological mechanisms, they share risk factors with AAA, such as hypertension and smoking. However, there is a need for a more in- -depth study of the key elements that may influence the formation and progression of a particular aneurysm to find ways of therapeutic intervention or search for a diagnostic tool. Today, it is known that the disruption of gene expression is one of the main mechanisms that contribute to the development of aneurysms. At the same time, growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of aneurysms. Although much has been studied of the known protein-coding genes, circular RNAs (circRNAs), a relatively new and rapidly evolving large family of transcripts, have recently received much scientific attention. CircRNAs regulate gene expression through the sponging of microRNAs (miRNAs) and can also be used as therapeutic targets and biomarkers. Increasing evidence has implicated circRNAs in the pathogenesis of multiple cardiovascular diseases, including the development of aneurysms. However, the mechanism of dysregulation of certain circRNAs in a particular aneurysm remains to be studied. The discovery of circRNAs has recently advanced our understanding of the latest mode of miRNAs/target genes regulation in the development and progression of IA and TAA/AAA. The aim of this study is to compare the expression profiles of circRNAs to search for similar or different effects of certain circRNAs on the formation and progression of IA and TAA/AAA.

Deacetylase SIRT2 Inhibition Promotes Microglial M2 Polarization Through Axl/PI3K/AKT to Alleviate White Matter Injury After Subarachnoid Hemorrhage.

White matter injury (WMI) subsequent to subarachnoid hemorrhage (SAH) frequently leads to an unfavorable patient prognosis. Previous studies have indicated that microglial M1 polarization following SAH results in the accumulation of amyloid precursor protein (APP) and degradation of myelin basic protein (MBP), thereby catalyzing the exacerbation of WMI. Consequently, transitioning microglial polarization towards the M2 phenotype (neuroprotective state) represents a potential therapeutic approach for reversing WMI. The SIRT2 gene is pivotal in neurological disorders such as neurodegeneration and ischemic stroke. However, its function and underlying mechanisms in SAH, particularly how it influences microglial function to ameliorate WMI, remain unclear. Our investigations revealed that in post-SAH, there was a temporal increase in SIRT2 expression, predominantly in the cerebral corpus callosum area, with notable colocalization with microglia. However, following the administration of the SIRT2 inhibitor AK-7, a shift in microglial polarization towards the M2 phenotype and an improvement in both short-term and long-term neuronal functions in rats were observed. Mechanistically, CO-IP experiments confirmed that SIRT2 can interact with the receptor tyrosine kinase Axl within the TAM receptor family and act as a deacetylase to regulate the deacetylation of Axl. Concurrently, the inhibition of SIRT2 by AK-7 can lead to increased expression of Axl and activation of the anti-inflammatory pathway PI3K/Akt signaling pathway, which regulates microglial M2 polarization and consequently reduces WMI. However, when Axl expression was inhibited by the injection of the shAxl virus into the lateral ventricles, the downstream signaling pathways were significantly suppressed. Rescue experiments also confirmed that the neuroprotective effects of AK-7 can be reversed by PI3K inhibitors. These data suggest that SIRT2 influences WMI by affecting microglial polarization through the Axl/PI3K/AKT pathway, and that AK-7 could serve as an effective therapeutic drug for improving neurological functions in SAH patients.

Hybrid Surgery for symptomatic chronic internal carotid artery occlusion: a single-center experience.

BACKGROUND: Patients with symptomatic chronic internal carotid artery occlusion (ICAO) face a high risk of recurrent stroke despite receiving aggressive medical therapy. This study aimed to evaluate the effectiveness and safety of hybrid surgery in treating symptomatic chronic ICAO. METHODS: This retrospective case series was conducted at a single center. From January 2019 to December 2022, patients with symptomatic chronic ICAO who underwent hybrid surgery were included. We collected baseline data, lesion characteristics, revascularization rates, perioperative complications, and follow-up outcomes. RESULTS: The study enrolled 27 patients, comprising 22 males and 5 females, with symptomatic chronic ICAO. The hybrid surgery achieved a technical success rate of 100% for revascularization (n = 27), with a perioperative complication rate of 14.8% (n = 4). Following a median follow-up of 6.0 months (IQR, 4-10), 21 patients underwent a DSA or CT angiography reexamination, confirming a vascular patency rate of 90.5% (n = 19). One patient required surgery for severe in-stent restenosis, and another experienced asymptomatic occlusion. Clinical follow-ups were conducted for all 26 patients; no new strokes were reported in the qualifying artery territory, with 13 patients scoring 0, 12 scoring 1, and 1 scoring 2 on the mRS. CONCLUSION: Although hybrid surgery represent a promising option for treating chronic ICAO, they are also associated with a relatively high incidence of treatment-related complications. The application of composite surgery should be based on standardized technical guidelines and the careful selection of patients who are genuinely at high risk for recurrent strokes.

Self-expanding intracranial drug-eluting stent system in patients with symptomatic intracranial atherosclerotic stenosis: initial experience and midterm angiographic follow-up.

BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke worldwide. In patients undergoing endovascular treatment for ICAS, in-stent restenosis (ISR) is associated with ischemic stroke recurrence. OBJECTIVE: Intracranial drug-eluting self-expanding stent systems (COMETIU; Sinomed Neurovita Technology Inc., CHN) are new devices for treating ICAS. This study evaluated the perioperative experience and medium-term outcomes of COMETIU in 16 patients. METHODS: We prospectively analyzed 16 patients with ICAS (≥ 70% stenosis) who underwent intravascular therapy between September 4, 2022, and February 1, 2023. The primary outcome was the incidence of ISR at 6 months postoperatively. The secondary efficacy outcomes were device and technical success rates. The secondary safety outcomes included stroke or death within 30 days after the procedure and the cumulative annual rate of recurrent ischemic stroke in the target-vessel territory from 31 days to 6 months and 1 year. RESULTS: A total of 16 patients with 16 intracranial atherosclerotic lesions were treated with 16 COMETIUs. All procedures were performed under general anesthesia with 100% device and technical success rates, with no cases of periprocedural stroke or death. The mean radiographic follow-up duration was at least 6 months postoperatively, and all patients presented for radiographic and clinical follow-up. There were no reported ischemic or hemorrhagic strokes. Angiographic follow-up for all patients revealed no cases of ISR. CONCLUSION: COMETIU is safe and effective for treating ICAS, with minimal risk during the procedure and a low rate of ISR during medium-term follow-up.

The crosstalk between oxidative stress and DNA damage induces neural stem cell senescence by HO-1/PARP1 non-canonical pathway.

Neural stem cells play a crucial role in maintaining brain homeostasis. Neural stem cells senescence can lead to the decline of nerve repair and regeneration, causing brain aging and neurodegenerative diseases. However, the mechanism underlying neural stem cells senescence remains poorly understood. In this study, we report a novel HO-1/PARP1 non-canonical pathway highlighting how oxidative stress triggers the DNA damage response, ultimately leading to premature cellular senescence in neural stem cells. HO-1 acts as a sensor for oxidative stress, while PARP1 functions as a sensor for DNA damage. The simultaneous expression and molecular interaction of these two sensors can initiate a crosstalk of oxidative stress and DNA damage response processes, leading to the vicious cycle. The persistent activation of this pathway contributes to the senescence of neural stem cells, which in turn plays a crucial role in the progression of neurodegenerative diseases. Consequently, targeting this novel signaling pathway holds promise for the development of innovative therapeutic strategies and targets aimed at mitigating neural stem cells senescence-related disorders.

Microsurgical clipping versus endovascular therapy for treating patients with middle cerebral artery aneurysms presenting with neurological ischemic symptoms.

Studies comparing different treatment methods in patients with middle cerebral artery (MCA) aneurysms in different subgroups of onset symptoms are lacking. It is necessary to explore the safety and efficacy of open surgical treatment and endovascular therapy in patients with MCA aneurysms in a specific population. This study aimed to compare microsurgical clipping versus endovascular therapy regarding complication rates and outcomes in patients with MCA aneurysms presenting with neurological ischemic symptoms. This was a retrospective cohort study in which 9656 patients with intracranial aneurysms were screened between January 2014 and July 2022. Further, 130 eligible patients were enrolled. The primary outcome was the incidence of serious adverse events (SAEs) within 30 days of treatment, whereas secondary outcomes included postprocedural target vessel-related stroke, disabling stroke or death, mortality, and aneurysm occlusion rate. Among the 130 included patients, 45 were treated with endovascular therapy and 85 with microsurgical clipping. The primary outcome of the incidence of SAEs within 30 days of treatment was significantly higher in the clipping group [clipping: 23.5%(20/85) vs endovascular: 8.9%(4/45), adjusted OR:4.05, 95% CI:1.20-13.70; P = 0.024]. The incidence of any neurological complications related to the treatment was significantly higher in the clipping group [clipping:32.9%(28/85) vs endovascular:15.6%(7/45); adjusted OR:3.49, 95%CI:1.18-10.26; P = 0.023]. Postprocedural target vessel-related stroke, disabling stroke or death, mortality rate, and complete occlusion rate did not differ significantly between the two groups. Endovascular therapy seemed to be safer in treating patients with MCA aneurysms presenting with neurological ischemic symptoms compared with microsurgical clipping, with a significantly lower incidence of SAEs within 30 days of treatment and any neurological complications related to the treatment during follow-up.

Therapeutic application of adipose-derived stromal vascular fraction in myocardial infarction.

The insufficiency of natural regeneration processes in higher organisms, including humans, underlies myocardial infarction (MI), which is one of the main causes of disability and mortality in the population of developed countries. The solution to this problem lies in the field of revealing the mechanisms of regeneration and creating on this basis new technologies for stimulating endogenous regenerative processes or replacing lost parts of tissues and organs with transplanted cells. Of great interest is the use of the so-called stromal vascular fraction (SVF), derived from autologous adipose tissue. It is known that the main functions of SVF are angiogenetic, antiapoptotic, antifibrotic, immune regulation, anti-inflammatory, and trophic. This study presents data on the possibility of using SVF, targeted regulation of its properties and reparative potential, as well as the results of research studies on its use for the restoration of damaged ischemic tissue after MI.

MicroRNAs in meningiomas: Potential biomarkers and therapeutic targets.

Meningiomas, characterized primarily as benign intracranial or spinal tumors, present distinctive challenges due to their variable clinical behavior, with certain cases exhibiting aggressive features linked to elevated morbidity and mortality. Despite their prevalence, the underlying molecular mechanisms governing the initiation and progression of meningiomas remain insufficiently understood. MicroRNAs (miRNAs), small endogenous non-coding RNAs orchestrating post-transcriptional gene expression, have garnered substantial attention in this context. They emerge as pivotal biomarkers and potential therapeutic targets, offering innovative avenues for managing meningiomas. Recent research delves into the intricate mechanisms by which miRNAs contribute to meningioma pathogenesis, unraveling the molecular complexities of this enigmatic tumor. Meningiomas, originating from arachnoid meningothelial cells and known for their gradual growth, constitute a significant portion of intracranial tumors. The clinical challenge lies in comprehending their progression, particularly factors associated with brain invasion and heightened recurrence rates, which remain elusive. This comprehensive review underscores the pivotal role of miRNAs, accentuating their potential to advance our comprehension of meningioma biology. Furthermore, it suggests promising directions for developing diagnostic biomarkers and therapeutic interventions, holding the promise of markedly improved patient outcomes in the face of this intricate and variable disease.

MiRNAs as new potential biomarkers and therapeutic targets in brain metastasis.

Brain metastases represent a formidable challenge in cancer management, impacting a significant number of patients and contributing significantly to cancer-related mortality. Conventional diagnostic methods frequently fall short, underscoring the imperative for non-invasive alternatives. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), present promising avenues for exploration. These ncRNAs exert influence over the prognosis and treatment resistance of brain metastases, offering valuable insights into underlying mechanisms and potential therapeutic targets. Dysregulated ncRNAs have been identified in brain metastases originating from various primary cancers, unveiling opportunities for intervention and prevention. The analysis of ncRNA expression in bodily fluids, such as serum and cerebrospinal fluid, provides a noninvasive means to differentiate brain metastases from primary tumors. NcRNAs, particularly miRNAs, assume a pivotal role in orchestrating the immune response within the brain microenvironment. MiRNAs exhibit promise in diagnosing brain metastases, effectively distinguishing between normal and cancer cells, and pinpointing the tissue of origin for metastatic brain tumors. The manipulation of miRNAs holds substantial potential in cancer treatment, offering the prospect of reducing toxicity and enhancing efficacy. Given the limited treatment options and the formidable threat of brain metastases in cancer patients, non-coding RNAs, especially miRNAs, emerge as beacons of hope, serving as both diagnostic tools and therapeutic targets. Further clinical studies are imperative to validate the specificity and sensitivity of ncRNAs, potentially reshaping approaches to tackle this challenge and elevate treatment outcomes for affected patients.

LAMC1 attenuates neuronal apoptosis via FAK/PI3K/AKT signaling pathway after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The poor prognosis in patients with subarachnoid hemorrhage (SAH) is often attributed to neuronal apoptosis. Recent evidence suggests that Laminin subunit gamma 1 (LAMC1) is essential for cell survival and proliferation. However, the effects of LAMC1 on early brain injury after SAH and the underlying mechanisms are unknown. The current study aimed to reveal the anti-neuronal apoptotic effect and the potential mechanism of LAMC1 in the rat and in the in vitro SAH models. METHODS: The SAH model of Sprague-Dawley rats was established by endovascular perforation. Recombinant LAMC1 (rLAMC1) was administered intranasally 30 min after modeling. LAMC1 small interfering RNA (LAMC1 siRNA), focal adhesion kinase (FAK)-specific inhibitor Y15 and PI3K-specific inhibitor LY294002 were administered before SAH modeling to explore the neuroprotection mechanism of rLAMC1. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. Subsequently, SAH grades, neurobehavioral tests, brain water content, blood-brain barrier permeability, western blotting, immunofluorescence, TUNEL, and Fluoro-Jade C staining were performed. RESULTS: The expression of endogenous LAMC1 was markedly decreased after SAH, both in vitro and in vivo. rLAMC1 significantly reduced the brain water content and blood-brain barrier permeability, improved short- and long-term neurobehavior, and decreased neuronal apoptosis. Furthermore, rLAMC1 treatment significantly increased the expression of p-FAK, p-PI3K, p-AKT, Bcl-XL, and Bcl-2 and decreased the expression of Bax and cleaved caspase -3. Conversely, knockdown of endogenous LAMC1 aggravated the neurological impairment, suppressed the expression of Bcl-XL and Bcl-2, and upregulated the expression of Bax and cleaved caspase-3. Additionally, the administration of Y15 and LY294002 abolished the protective roles of rLAMC1. In vitro, rLAMC1 significantly reduced neuronal apoptosis, and the protective effects were also abolished by Y15 and LY294002. CONCLUSION: Exogenous LAMC1 treatment improved neurological deficits after SAH in rats, and attenuated neuronal apoptosis in both in vitro and in vivo SAH models, at least partially through the FAK/PI3K/AKT pathway.

Integrative bioinformatics analysis of miRNA and mRNA expression profiles and identification of associated miRNA-mRNA network in intracranial aneurysms.

Background: Intracranial aneurysms (IAs) represent protrusions in the vascular wall, with their growth and wall thinning influenced by various factors. These processes can culminate in the rupture of the aneurysm, leading to subarachnoid hemorrhage (SAH). Unfortunately, over half of the patients prove unable to withstand SAH, succumbing to adverse outcomes despite intensive therapeutic interventions, even in premier medical facilities. This study seeks to discern the pivotal microRNAs (miRNAs) and genes associated with the formation and progression of IAs. Methods: The investigation gathered expression data of miRNAs (from GSE66240) and mRNAs (from GSE158558) within human aneurysm tissue and superficial temporal artery (STA) samples, categorizing them into IA and normal groups. This classification was based on the Gene Expression Omnibus (GEO) database. Results: A total of 70 differentially expressed microRNAs (DEMs) and 815 differentially expressed mRNAs (DEGs) were pinpointed concerning IA. Subsequently, a miRNA-mRNA network was constructed, incorporating 9 significantly upregulated DEMs and 211 significantly downregulated DEGs. Simultaneously, functional enrichment and pathway analyses were conducted on both DEMs and DEGs. Through protein-protein interaction (PPI) network analysis and functional enrichment, 9 significantly upregulated DEMs (hsa-miR-188-5p, hsa-miR-590-5p, hsa-miR-320b, hsa-miR-423-5p, hsa-miR-140-5p, hsa-miR-486-5p, hsa-miR-320a, hsa-miR-342-3p, and hsa-miR-532-5p) and 50 key genes (such as ATP6V1G1, KBTBD6, VIM, PA2G4, DYNLL1, METTL21A, MDH2, etc.) were identified, suggesting their potential significant role in IA. Among these genes, ten were notably negatively regulated by at least two key miRNAs. Conclusions: The findings of this study provide valuable insights into the potential pathogenic mechanisms underlying IA by elucidating a miRNA-mRNA network. This comprehensive approach sheds light on the intricate interplay between miRNAs and genes, offering a deeper understanding of the molecular dynamics involved in IA development and progression.

Risk Factors for Cerebral Hyperperfusion Syndrome After Combined Revascularization in Adult Patients with Moyamoya Disease.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is known as a complication after bypass surgery for Moyamoya disease (MMD). However, the incidence of CHS has not been accurately reported, and there is no consensus on the risk factors associated with it. AIM: The aim of this study was to determine the risk factors associated with postoperative CHS after surgical combined revascularization used to treat adult patients with MMD. OBJECTIVE: To assess the frequency and characteristics of CHS in patients with MMD after revascularization operations. METHODS: Patients who received combined revascularization from Jan 2021 to Nov 2022 were retrospectively reviewed. Preoperative clinical characteristics and radiographic features were recorded. Postoperative CHS after surgery were examined. Multivariate logistic regression analyses were performed to identify the risk factors for CHS. RESULTS: A total of 133 patients (141 hemispheres) were included in this study. Postoperative CHS were observed in 28 hemispheres (19.8%), including focal cerebral hyperperfusion syndrome (FCHS) in 20 hemispheres (14.2%), hemorrhage in 4 (2.8%) hemispheres, seizures in 4 (2.8%) hemispheres. The results of multivariate logistic regression analysis indicated that preoperative hypertension (OR 4.705, 95% CI 1.323 ~ 12.554, p = 0.014), cerebral hemorrhage onset (OR 5.390, 95% CI 1.408 ~ 20.642, p = 0.014) and higher Hct level (OR 1.171, 95% CI 1.051 ~ 1.305, p = 0.004) were significantly associated with CHS after combined revascularization. CONCLUSIONS: Preoperative hypertension, cerebral hemorrhage onset, and higher Hct level were independent risk factors for CHS after combined revascularization.

Effect of Time Window on Endovascular Thrombectomy with or without Intravenous Thrombolysis in Acute Ischemic Stroke: Results from DIRECT-MT.

INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.

Intra-arterial tenecteplase during thrombectomy for acute stroke (BRETIS-TNK II): rationale and design.

BACKGROUND: Our recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischaemic stroke (AIS) patients with large-vessel occlusion (LVO). AIMS: To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom onset. SAMPLE SIZE ESTIMATES: A maximum of 380 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by age, gender, baseline systolic blood pressure, prestroke modified Rankin Scale (mRS), baseline National Institute of Health stroke scale, baseline ASPECTS, time from onset to groin puncture, intravenous thrombolysis before EVT, stroke territory and stroke aetiology. DESIGN: Intra-arterial TNK during thrombectomy for acute stroke (BRETIS-TNK II) study is a prospective, randomised, adaptive enrichment, open-label, blinded end point, multicentre study. Eligible AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:1. The experimental group will be treated with intra-arterial infusion of TNK during EVT. The control group will be treated with standard EVT. OUTCOME: The primary end point is a favourable outcome, defined as an mRS score of 0-2 at 90 days. The primary safety end point is symptomatic intracranial haemorrhage within 48 hours, which is defined as an increase in the National Institutes of Health Stroke Scale score of ≥4 points as a result of the intracranial haemorrhage. CONCLUSIONS: The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect: a large Chinese cohort.

BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.

Circular RNAs in intracranial aneurysms: Emerging roles in pathogenesis, diagnosis and therapeutic intervention.

Intracranial aneurysms (IAs) present a substantial health threat, given the potential for catastrophic ruptures and subarachnoid hemorrhages (SAH). Swift and effective measures for diagnosis and treatment are paramount to enhance patient outcomes and alleviate the associated healthcare burden. In this context, circular RNAs (circRNAs) have emerged as an intriguing area of investigation, offering promise as both diagnostic biomarkers and therapeutic targets for IAs. CircRNAs have demonstrated their influence on critical molecular and cellular processes underpinning IAs pathogenesis, revealing their pivotal role in understanding this complex ailment. Beyond their diagnostic potential, circRNAs hold great potential as prognostic markers, providing crucial insights into IAs rupture risk. The unique circular structure and their regulatory functions make circRNAs an enticing avenue for innovative therapeutic approaches. The ongoing study of circRNAs in the context of IAs is an exciting and rapidly evolving field that has the potential to revolutionize approaches to diagnosis, treatment, and prevention of this life-threatening condition. As research continues to unravel the intricate roles of circRNAs, they are poised to become invaluable tools in clinical practice, enhancing patient care and ultimately reducing the impact of cerebral aneurysms on both individuals and healthcare systems. This comprehensive review delves deeply into the world of circRNAs in the realm of IAs, elucidating their multifaceted roles in the onset and progression of this condition. Moreover, this review ventures into the diagnosis and therapeutic potential of circRNAs, exploring their possible applications in gene therapy and as targets for novel treatment modalities.

CircRNAs in Alzheimer's disease: What are the prospects?

Circular RNAs (circRNAs) is a fascinating covalently closed circular non-coding RNA that is abundantly present in the transcriptome of eukaryotic cells. Its versatile nature allows it to participate in a multitude of pathological and physiological processes within the organism. One of its crucial functions is acting as a microRNA sponge, modulating protein transcription levels, and forming interactions with essential RNA-binding proteins. Remarkably, circRNAs demonstrates a specific enrichment in various vital areas of the brain, including the cortex, hippocampus, white matter, and photoreceptor neurons, particularly in aging organisms. This intriguing characteristic has led scientists to explore its potential as a significant biological marker of neurodegeneration, offering promising insights into neurodegenerative diseases like Alzheimer's disease (AD). In AD, there has been an interesting observation of elevated levels of circRNAs in both peripheral blood and synaptic terminals of affected individuals. This intriguing finding raises the possibility that circRNAs may have a central role in the initiation and progression of AD. Notably, different categories of circRNAs, including HDAC9, HOMER1, Cwc27, Tulp4, and PTK2, have been implicated in driving the pathological changes associated with AD through diverse mechanisms. For instance, these circRNAs have been demonstrated to contribute to the accumulation of beta-amyloid, which is a hallmark characteristic of AD. Additionally, these circRNAs contribute to the excessive phosphorylation of tau protein, a phenomenon associated with neurofibrillary tangles, further exacerbating the disease. Moreover, they are involved in aggravating neuroinflammation, which is known to play a critical role in AD's pathogenesis. Lastly, these circRNAs can cause mitochondrial dysfunction, disrupting cellular energy production and leading to cognitive impairment. As researchers delve deeper into the intricate workings of circRNAs, they hope to unlock its full potential as a diagnostic tool and therapeutic target for neurodegenerative disorders, paving the way for innovative treatments and better management of such devastating conditions.

Methylated MFGE8 Promotes Early Brain Injury After Subarachnoid Hemorrhage and Inhibiting Autophagy of Nerve Cell.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) is a relatively common clinical hemorrhagic stroke crisis. The important role of early brain injury (EBI) and autophagy in SAH has been increasingly recognized in recent years. This study aims to investigate the function and the undergoing mechanism of MFGE8 in EBI after SAH. METHODS: SAH model was established using C57BL/6 mice, and the SAH cell model was constructed by oxy-hemoglobin (Oxy-Hb) induced BV2 and SH-SY5Y co-culture system. Various methods were used to detect EBI and autophagy after SAH in mouse/cell lines, including mouse neurological function score, wet/dry method, HE and Evans blue staining, etc. The effect on EBI was explored after knockdown or overexpression of key genes DNMT1, MFGE8, and P2X7R. MSP was used to detect the methylation of MFGE8 promoter region, and ChIP was used to detect the binding relationship between DNMT1 and MFGE8 promoter region. RESULTS: The results showed that the activation of autophagy attenuates EBI in SAH mice. Increased level of DNMT1 and decreased level of MFGE8 were observed in brain tissues of SAH mice. Knockdown of DNMT1 or overexpression of MFGE8 attenuates EBI in mice by promoting autophagy. At the same time, we found that DNMT1 promotes methylation of MFGE8 promoter region and suppresses its protein levels. MFGE8 downregulates P2X7R levels and subsequently activates PI3k/Akt/mTOR axis, promotes autophagy, and attenuates EBI in SAH mice. CONCLUSION: DNMT1 promotes the methylation of MFGE8 promoter region and downregulates MFGE8 level; restoring MFGE8 downregulates P2X7R, and promotes autophagy by limiting the activation of PI3k/Akt/mTOR, thus exerting a protective effect on brain tissue of SAH mice. HIGHLIGHTS: • High expression of DNMT1 and P2X7R and low expression of MFGE8 were observed in SAH mice. • Activation of autophagy reduces EBI after SAH in mice. • DNMT1/MFGE8 reduces autophagy in EBI after SAH in both mouse and cell models. • DNMT1 targets the MFGE8 promoter to upregulate its methylation level. • MFGE8 inhibits P2X7R to activate PI3k/AKT/mTOR pathway and autophagy, thus inhibiting EBI after SAH.