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Infratentorial Cerebral Cavernous Malformation May be a Risk Factor for Symptomatic Bleeding and Precocity of Symptoms: A Multicenter, Propensity Score Matched, Case-Control Study. 脑室下腔隙脑海绵畸形可能是症状性出血和症状出现过早的风险因素:一项多中心、倾向评分匹配、病例对照研究。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026304601240307051654
Gustavo da Fontoura Galvão, Ricardo Castro Filho, Alexandre Alexandre Martins Cunha, Andre Guimarães Soares, Marcos Antônio Dellaretti Filho, Jorge Marcondes de Souza

Background: Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable.

Objective: Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease.

Methods: We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life.

Results: The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03).

Conclusion: Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.

背景:脑空洞畸形(CCM)是中枢神经系统血管畸形中最常见的类型之一。脑出血、癫痫发作和病灶增生是其主要临床表现。目的:在此,我们对一个多中心 CCM 队列进行了分析,以寻找患有脑室上和/或脑室下海绵畸形的患者的不同临床数据,从而更好地了解这种独特神经外科疾病的解剖位置所涉及的风险因素:我们介绍了一项多中心、倾向评分匹配(PSM)、病例对照研究,包括2017年5月至2022年12月期间在三个不同神经外科中心接受临床评估的149例连续CCM病例。流行病学数据是在每次临床评估时定义的。逻辑回归用于确定每个可能的风险因素对出血风险的独立贡献。为了平衡有症状和无症状患者之间的基线协变量,特别是有症状出血和无症状出血患者之间的协变量,我们采用了PSM策略。我们绘制了 Kaplan-Meier 曲线,以评估是否存在脑室下病变的患者在生命早期出血的几率更大:结果:在将出血风险与纯粹无症状者进行比较的多变量分析中,存在脑室下病变是一个风险因素(OR:3.23,95% CI 1.43 - 7.26,P = 0.005)。此外,在 PSM 后,脑室下 CCM 也是一个风险因素(OR:4.56,95% CI 1.47 - 14.10,P = 0.008)。在总体队列中(P = 0.0328)和 PSM 组中(P = 0.03),将首次出血时间与所有其他临床表现进行比较,发现存在脑室下病变与症状的早发有关:在此,我们提供了一些证据,证明脑室内脑腔畸形的临床表现可能更具侵袭性,是出现症状性出血和出血过早的危险因素。
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引用次数: 0
Risk Factors and Prognosis of Early Neurological Deterioration after Bridging Therapy. 桥接疗法后早期神经功能恶化的风险因素和预后。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026287986240104074006
Yiju Xie, Shengyu Li, Liuyu Liu, Shiting Tang, Yayuan Liu, Shuangquan Tan, Zhijian Liang

Background: Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes.

Objective: We aimed to study the incidence, risk factors and prognosis of END after BT.

Methods: From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors.

Results: The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001).

Conclusion: It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.

背景:急性缺血性卒中(AIS)患者桥接治疗(BT)后的早期神经功能恶化(END)与不良预后有关:我们旨在研究 BT 后 END 的发生率、风险因素和预后:方法:分析了 2021 年 1 月至 12 月期间,三家综合卒中中心采用 BT(机械取栓前使用阿替普酶静脉溶栓)治疗 AIS 患者的临床数据。根据患者是否在症状出现后 72 小时内出现END,将其分为非END 组和END 组。采用改良Rankin量表(mRS)评估患者90天后的预后,mRS≤2为预后良好。对END的发生率进行了调查,并采用二元逻辑回归分析探讨其相关因素:结果:BT术后END发生率为33.67%。符合条件的 90 例患者中,END 组 29 例,非END 组 61 例。多变量逻辑回归分析显示,收缩压(SBP)升高(OR=1.026,95%CI:1.001-1.051,P =0.043)、入院时血糖水平升高(OR=1.389,95%CI:1.092-1.176,P =0.007)和大动脉粥样硬化(LAA)亚型(OR=8.009,95%CI:2.357-27.223,P =0.001)是END的独立危险因素。与非END组相比,END组的良好预后率明显较低(6.90%对65.57%,P =0.001),而死亡率较高(44.83%对4.92%,P =0.001):结论:研究发现,AIS 患者 BT 后 END 的发生率为 33.67%。SBP升高、入院时血糖水平升高和LAA是END的独立危险因素,预示着不良预后。
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引用次数: 0
Predictors of Emboli in Mechanical Thrombectomy for Anterior Circulation Stroke. 前循环中风机械取栓术中栓塞的预测因素
Pub Date : 2024-01-01 DOI: 10.2174/0115672026298727240219110134
Yongho Kwon, Ho Jun Yi, Dong-Seong Shin, Bum-Tae Kim

Objective: Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT.

Methods: Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli.

Results: Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; p = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; p = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; p = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; p = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; p = 0.029) were associated with occurrence of emboli.

Conclusion: MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.

目的:栓塞通常发生在机械血栓切除术(MT)中。本研究旨在分析 MT 术后栓塞的预测因素:方法:纳入因前循环闭塞接受机械取栓术并成功再灌注的患者。栓子包括数字减影血管造影(DSA)中的远端栓子和弥散加权成像(DWI)中无远端栓子的意外栓塞。对基线特征、手术细节、血管造影结果和临床结果进行了回顾。进行了多变量分析,以评估发生栓塞的预测因素:结果:在601名患者中,149名(24.8%)患者在DSA检查中发现远端栓子,169名(28.1%)患者即使在DSA检查中没有发现远端栓子,但在DWI检查中也出现了意外的栓塞梗死。共有 318 名(52.9%)患者被纳入栓塞组,283 名(47.1%)患者被纳入非栓塞组。92;P = 0.014)、BGC 早期球囊化(OR 0.68,95% CI 0.50-0.90;P = 0.009)和较长的支架回缩器(OR 0.72,95% CI 0.54-0.90;P = 0.029)与栓子的发生有关:结论:仅使用支架牵引器的 MT、使用较大的微导管和血栓通过可能会增加栓塞风险。相比之下,接触式抽吸血栓切除术、使用 BGC、BGC 早期球囊化以及使用较长的支架回取器可以降低栓塞发生的几率。
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引用次数: 0
Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19. 电针通过lncRNA H19的m6A甲基化调控S1PR2/TLR4/NLRP3信号通路缓解脑缺血再灌注损伤
Pub Date : 2024-01-01 DOI: 10.2174/0115672026294183240207115956
Han-Rui Zhang, Gu-Quan Ma, He-Qun Lv, Yao-Ting Feng, Yong-Jun Peng

Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated.

Methods: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment.

Results: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation.

Conclusion: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.

电针(EA)治疗对脑缺血再灌注损伤(CIR)具有保护作用。然而,其潜在的分子机制仍未完全阐明:所有大鼠随机分为五组:SHAM组、MCAO组、MCAO+EA(MEA)组、MCAO+METTL3过表达+EA(METTL3)组和MCAO+lncRNA H19过表达+EA(lncRNA H19)组。建立大脑中动脉闭塞(MCAO)大鼠以模拟CIR损伤。通过向大鼠侧脑室立体定向注射慢病毒诱导lncRNA H19和METTL3的过表达。MEA组、METTL3组和lncRNA H19组大鼠在 "人中"(DU26)和 "百会"(DU20)穴位(3.85/6.25Hz;1mA)上接受EA治疗。此外,本实验还检测了神经功能缺损评分、脑梗死面积、脑组织病理变化、总RNA m6A水平以及METTL3、S1PR2、TLR4、NLRP3和lncRNA H19的表达:结果:EA改善了MCAO大鼠的神经功能缺损评分、脑梗死面积和病理损伤,而过表达METTL3或lncRNA H19则减弱了EA对CIR损伤的有益影响。更重要的是,EA 下调了 MCAO 大鼠的总 RNA m6A 水平以及 METTL3、S1PR2、TLR4、NLRP3 和 lncRNA H19 的表达。相反,过表达 METTL3 或 lncRNA H19 可逆转 EA 诱导的下调:研究结果表明,EA可能通过lncRNA H19的m6A甲基化下调S1PR2/TLR4/NLRP3信号通路,从而缓解CIR损伤。我们的研究结果为EA对CIR损伤的分子机制提供了新的见解。
{"title":"Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.","authors":"Han-Rui Zhang, Gu-Quan Ma, He-Qun Lv, Yao-Ting Feng, Yong-Jun Peng","doi":"10.2174/0115672026294183240207115956","DOIUrl":"10.2174/0115672026294183240207115956","url":null,"abstract":"<p><p>Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated.</p><p><strong>Methods: </strong>All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on \"Renzhong\" (DU26) and \"Baihui\" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment.</p><p><strong>Results: </strong>EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation.</p><p><strong>Conclusion: </strong>The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"64-73"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial Intelligence and Disease Signature Pathways: Driving Innovation to Elucidate Underlying Pathogenic Mechanisms. 人工智能与疾病特征途径:推动创新,阐明潜在的致病机制。
Pub Date : 2024-01-01 DOI: 10.2174/1567202621999240621122700
Kenneth Maiese
{"title":"Artificial Intelligence and Disease Signature Pathways: Driving Innovation to Elucidate Underlying Pathogenic Mechanisms.","authors":"Kenneth Maiese","doi":"10.2174/1567202621999240621122700","DOIUrl":"10.2174/1567202621999240621122700","url":null,"abstract":"","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"229-233"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crocetin Enhances Temozolomide Efficacy in Glioblastoma Therapy Through Multiple Pathway Suppression. 克洛西汀通过多途径抑制增强替莫唑胺对胶质母细胞瘤的疗效
Pub Date : 2024-01-01 DOI: 10.2174/0115672026332275240731054001
Wei-En Tsai, Yen-Tsen Liu, Fu-Hsuan Kuo, Wen-Yu Cheng, Chiung-Chyi Shen, Ming-Tsang Chiao, Yu-Fen Huang, Yea-Jiuen Liang, Yi-Chin Yang, Wan-Yu Hsieh, Jun-Peng Chen, Szu-Yuan Liu, Cheng-Di Chiu

Background: Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells.

Methods: Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 μM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects.

Results: Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others.

Conclusion: Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.

背景:多形性胶质母细胞瘤(GBM多形性胶质母细胞瘤(GBM)是一种侵袭性脑肿瘤,很难通过手术切除。研究表明,藏红花中的物质,即藏红花素和藏红花苷,可以成为有效的天然疗法,显示出杀死癌细胞的能力:我们的研究重点是利用 U87 细胞系评估藏红花素对神经胶质瘤的影响。我们特别研究了藏红花素如何影响胶质瘤细胞的存活、生长和扩散,探讨了其在 75-150 μM 浓度范围内的影响。研究还包括藏红花素与化疗药物替莫唑胺(TMZ)的联合实验,以评估潜在的协同效应:结果:西红花素能明显降低胶质瘤细胞的活力、增殖和迁移。它通过降低基质金属肽酶9(MMP-9)和Ras同源家族成员A(RhoA)的水平来达到上述效果。此外,藏红花酸还能抑制肿瘤生长所需的细胞结构的形成。它阻断了对癌细胞存活至关重要的 Ak Strain Transforming(AKT)信号通路的多个点。这种治疗方法增加了胶质瘤细胞的死亡并破坏了细胞周期。在与 TMZ 联合使用时,西西替酯不仅能增强减少癌细胞生长的作用,还能促进细胞死亡和减少细胞复制。这种联合疗法进一步降低了高迁移率基团框 1(HMGB1)和高级糖化终产物受体(RAGE)的水平,这些蛋白与炎症和肿瘤进展有关。它选择性地抑制了参与细胞应激反应的某些途径,而不影响其他途径:我们的研究结果凸显了西番莲素治疗胶质瘤的潜力。它针对肿瘤生长和扩散的各种机制,提供了多种治疗途径。进一步的研究对于充分了解和利用藏红花素治疗胶质瘤的益处至关重要。
{"title":"Crocetin Enhances Temozolomide Efficacy in Glioblastoma Therapy Through Multiple Pathway Suppression.","authors":"Wei-En Tsai, Yen-Tsen Liu, Fu-Hsuan Kuo, Wen-Yu Cheng, Chiung-Chyi Shen, Ming-Tsang Chiao, Yu-Fen Huang, Yea-Jiuen Liang, Yi-Chin Yang, Wan-Yu Hsieh, Jun-Peng Chen, Szu-Yuan Liu, Cheng-Di Chiu","doi":"10.2174/0115672026332275240731054001","DOIUrl":"10.2174/0115672026332275240731054001","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells.</p><p><strong>Methods: </strong>Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 μM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects.</p><p><strong>Results: </strong>Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others.</p><p><strong>Conclusion: </strong>Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"320-336"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increased Cyclic Adenosine Monophosphate Responsive Element is Closely Associated with the Pathogenesis of Drug-resistant Epilepsy. 单磷酸环磷酸腺苷反应元件的增加与耐药性癫痫的发病机制密切相关。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026290996240307072539
Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu

Background: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA.

Objective: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE.

Methods: The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABAA receptor α1, β2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR.

Results: The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABAA receptors α1, β2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy.

Conclusion: Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABAA receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.

背景:耐药性癫痫(DRE)是一种难治性神经系统疾病。大量证据表明,γ-氨基丁酸-a(GABAA)受体可能是导致癫痫耐药性产生的机制之一。人们还知道,cAMP 反应元件结合蛋白(CREB)在 GABAA 的转录调控中可能起着关键作用:本研究探讨了 CREB 在 DRE 发病中的作用,以及 CREB 对 DRE 中 GABA 相关受体的影响:方法:通过慢病毒转染增加或减少正常大鼠海马中CREB的表达,然后对其进行锂-匹罗卡品诱导的癫痫模型试验。苯巴比妥钠(PB)和卡马西平(CBZ)用于选择耐药癫痫模型。通过Western印迹和荧光定量PCR检测大鼠海马中GABAA受体α1、β2和γ2亚基以及CREB蛋白的表达水平:结果:与对照组相比,过表达组大鼠癫痫发作的频率和持续时间增加。此外,表达减少组的癫痫发作严重程度、频率和持续时间均有所下降。对海马CREB蛋白和CREB mRNA表达水平的分析也得出了类似的结果。改变大鼠海马中CREB蛋白的表达可负向调节GABAA受体α1、β2和γ2的表达和转录水平,这表明CREB可能是开发癫痫治疗方案和药物的潜在靶点:我们的研究表明,CREB表达的增强会促进DRE的发生,并负向调节GABAA受体水平,抑制CREB的表达可降低DRE的发病率。
{"title":"Increased Cyclic Adenosine Monophosphate Responsive Element is Closely Associated with the Pathogenesis of Drug-resistant Epilepsy.","authors":"Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu","doi":"10.2174/0115672026290996240307072539","DOIUrl":"10.2174/0115672026290996240307072539","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABA<sub>A</sub>.</p><p><strong>Objective: </strong>This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE.</p><p><strong>Methods: </strong>The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABA<sub>A</sub> receptor α1, β2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR.</p><p><strong>Results: </strong>The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABA<sub>A</sub> receptors α1, β2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy.</p><p><strong>Conclusion: </strong>Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABA<sub>A</sub> receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"54-63"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study. 美国成年人氧化平衡评分与严重头痛或偏头痛之间的关系 一项横断面研究。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026298542240130053315
Dandan Geng, Huanxian Liu, Haoyuan Wang, Zhao Dong, Hebo Wang

Background: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored.

Objective: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults.

Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation.

Results: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively.

Conclusion: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.

背景:偏头痛与氧化应激有关:偏头痛与氧化应激有关。氧化平衡评分(OBS)可评估饮食和生活方式对疾病中氧化和抗氧化平衡的综合影响。然而,OBS 与偏头痛之间的关系仍未得到充分探讨:我们旨在研究 OBS 与美国成年人严重头痛或偏头痛之间的关系:这项横断面研究利用了美国国家健康与营养调查(NHANES)1999-2004 年的数据,通过自我报告来定义严重头痛或偏头痛,并通过 16 个日记和 4 个生活方式因素来计算 OBS。研究采用多变量加权逻辑回归模型来探讨OBS与偏头痛的关系,并进行分层分析以验证结果:研究纳入了 6653 名参与者(平均年龄 45.6 岁,52.1% 为男性),19.1% 的参与者报告了严重头痛或偏头痛。OBS与严重头痛或偏头痛之间存在明显的反向关系,调整后的几率比(OR)为0.97(95% [置信区间] CI:0.96,0.98,P <0.001)。与最低OBS三分位数相比,最高OBS三分位数的调整OR为0.58(95% CI:0.47,0.73)。这种模式在不同性别之间是一致的,男性的调整OR值为0.98(0.95,1.00),女性为0.97(0.95,1.00)。男性和女性偏头痛的调整OR值在最高三等分中分别为0.61(0.44,0.87)和0.54(0.37,0.79):该研究强调了 OBS 与严重头痛或偏头痛之间的显著关联,表明氧化应激在这些病症中的潜在作用。研究结果强调了均衡、富含抗氧化剂的饮食和生活方式对控制严重头痛或偏头痛的重要性。
{"title":"Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study.","authors":"Dandan Geng, Huanxian Liu, Haoyuan Wang, Zhao Dong, Hebo Wang","doi":"10.2174/0115672026298542240130053315","DOIUrl":"10.2174/0115672026298542240130053315","url":null,"abstract":"<p><strong>Background: </strong>Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored.</p><p><strong>Objective: </strong>We aimed to examine the relationship between OBS and severe headaches or migraines among American adults.</p><p><strong>Methods: </strong>This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine <i>via</i> self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation.</p><p><strong>Results: </strong>The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively.</p><p><strong>Conclusion: </strong>The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.</p>","PeriodicalId":93965,"journal":{"name":"Current neurovascular research","volume":" ","pages":"139-147"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Duration of Intracranial Pressure Increase after Aneurysmal Subarachnoid Hemorrhage: Prognostic Factors and Association with the Outcome. 动脉瘤性蛛网膜下腔出血后颅内压升高的持续时间:预后因素及其与预后的关系
Pub Date : 2024-01-01 DOI: 10.2174/0115672026312548240610104504
Pikria Ketelauri, Meltem Gümüs, Hanah Hadice Gull, Maryam Said, Laurel Rauschenbach, Thiemo Florin Dinger, Mehdi Chihi, Marvin Darkwah Oppong, Yahya Ahmadipour, Philipp Dammann, Karsten Henning Wrede, Ulrich Sure, Ramazan Jabbarli

Objective: A rupture of the intracranial aneurysm is frequently complicated, with an increase of intracranial pressure (ICP) requiring conservative and/or surgical treatment. We analyzed the risk factors related to the duration of pathologic ICP increase and the relationship between ICP burden and the outcome of subarachnoid hemorrhage (SAH).

Methods: Consecutive cases with aneurysmal SAH treated at our institution between 01/2003 and 06/2016 were eligible for this study. Different admission variables were evaluated to predict the duration of ICP increase >20 mmHg in univariate and multivariate analyses. The association of the ICP course with SAH outcome parameters (risk of cerebral infarction, in-hospital mortality, and unfavorable outcome at 6 months defined as modified Rankin scale >3) was adjusted for major outcome-relevant confounders.

Results: Of 820 SAH patients, 378 individuals (46.1%) developed at least one ICP increase requiring conservative and/or surgical management after aneurysm treatment (mean duration: 1.76 days, range: 1 - 14 days). In the multivariable linear regression analysis, patients' age (unstandardized coefficient [UC]=-0.02, p <0.0001), World Federation of Neurosurgical Societies (WFNS) grade 4-5 at admission (UC=0.71, p <0.004), regular medication with the angiotensinconverting enzyme (ACE) inhibitors (UC=-0.61, p =0.01), and presence of intracerebral hemorrhage (UC=0.59, p =0.002) were associated with the duration of ICP increase. In turn, patients with longer ICP elevations were at higher risk for cerebral infarction (adjusted odds ratio [aOR]=1.32 per-day-increase, p <0.0001), in-hospital mortality (aOR=1.30, p <0.0001) and unfavorable outcome (aOR=1.43, p <0.0001). SAH patients who underwent primary decompressive craniectomy (DC) showed shorter periods of ICP increase than patients with a secondary decompression (mean: 2.8 vs 4.9 days, p <0.0001).

Conclusion: The duration of ICP increase after aneurysm rupture is a strong outcome predictor and is related to younger age and higher initial severity of SAH. Further analysis of the factors impacting the course of ICP after SAH is essential for the optimization of ICP management and outcome improvement.

目的:颅内动脉瘤破裂通常比较复杂,颅内压(ICP)升高需要保守和/或手术治疗。我们分析了与病理性 ICP 增高持续时间相关的风险因素,以及 ICP 负担与蛛网膜下腔出血(SAH)预后之间的关系:方法:2003年1月至2016年6月在我院接受治疗的动脉瘤性SAH连续病例均符合本研究的条件。在单变量和多变量分析中,对不同的入院变量进行了评估,以预测ICP升高>20 mmHg的持续时间。ICP持续时间与SAH预后参数(脑梗死风险、院内死亡风险和6个月时的不良预后,即改良Rankin量表>3)之间的关系已根据主要预后相关混杂因素进行了调整:在820名SAH患者中,有378人(46.1%)在动脉瘤治疗后出现至少一次ICP增高,需要保守和/或手术治疗(平均持续时间:1.76天,范围:1 - 14天)。在多变量线性回归分析中,患者的年龄(非标准化系数 [UC]=-0.02, p 结论:患者的年龄与动脉瘤治疗后 ICP 增高的持续时间有关:动脉瘤破裂后 ICP 增高的持续时间是一个很强的结果预测因子,与年龄较小、SAH 初始严重程度较高有关。进一步分析影响 SAH 后 ICP 病程的因素对于优化 ICP 管理和改善预后至关重要。.
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引用次数: 0
A Study on the Effects of Different Positions on the Clinical Prognosis of Patients with Acute Ischemic Stroke. 不同体位对急性缺血性中风患者临床预后的影响研究。
Pub Date : 2024-01-01 DOI: 10.2174/0115672026316069240502120918
Qinqin Dai, Mengmeng Zhang, Yuanli Guo, Qilan Tang, Aixia Wang, Yuming Xu, Kai Liu

The key to treating Acute Ischemic Stroke (AIS) is to rapidly reopen occluded blood vessels, restore blood flow, and rescue the ischemic penumbra. Treatment methods mainly include thrombolysis, endovascular intervention, etc. However, these treatments are limited by strict time windows and technical conditions. Simpler and more feasible methods to improve cerebral blood flow are currently a hot topic in clinical research. In recent years, several studies have shown that changes in body position can effectively improve cerebral blood flow in patients. However, the effect on the neurological functional prognosis of AIS remains inconclusive. This review has examined the effects of changes in body position on the clinical prognosis of AIS, combining relevant guidelines and the latest research. The study has provided evidence of an improvement in the clinical prognosis of AIS.

治疗急性缺血性脑卒中(AIS)的关键是迅速再通闭塞血管,恢复血流,抢救缺血半影。治疗方法主要包括溶栓、血管内介入治疗等。然而,这些治疗方法受到严格的时间窗口和技术条件的限制。更简单、更可行的改善脑血流的方法是目前临床研究的热点。近年来,多项研究表明,改变体位可以有效改善患者的脑血流量。然而,其对 AIS 神经功能预后的影响仍无定论。本综述结合相关指南和最新研究,探讨了体位改变对 AIS 临床预后的影响。该研究为改善 AIS 的临床预后提供了证据。
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引用次数: 0
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Current neurovascular research
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