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Efficacy and safety of remimazolam versus propofol for intraoperative sedation during regional anesthesia: A phase II, multicenter, randomized, active-controlled, single-blind clinical trial 区域麻醉术中镇静用瑞咪唑安定与异丙酚的疗效和安全性:多中心、随机、主动对照、单盲临床试验II期
Pub Date : 2024-06-16 DOI: 10.1002/ibra.12163
Ting-Ting Li, Lu Yin, Yue-Xin Huang, Xiu-Hong Wang, Yan-Huan Wei, Yong Wang, Shi-Wei Yang, Genoveva B. da Graca Cunha, Fei Liu

This study aimed to evaluate the efficacy and safety of remimazolam for intraoperative sedation during regional anesthesia. It was a phase II-multicenter, randomized, single-blind, parallel-group, active-controlled clinical trial (No. ChiCTR2100054956). From May 6, 2021 to July 4, 2021, patients were randomly enrolled from 17 hospitals in China. A total of 105 patients aged 18–65 years who underwent selective surgery under regional anesthesia were included. Patients received different sedatives with different dosages: 0.1 mg/kg remimazolam (HR), 0.05 mg/kg remimazolam (LR), or 1.0 mg/kg propofol (P) group, followed by a maintenance infusion. Main outcome measures included the efficacy of sedation measured by Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) levels (1–4, 1–3, 2–3, 3, and 2–4) during the sedation procedure (the duration percentage) and incidence of adverse reactions. It showed that the duration percentage of MOAA/S levels 1–4 was 100.0 [8.1]% (median [interquartile range]), 89.9 [20.2]%, 100.0 [7.7]% in the HR, LR, and P groups, respectively. The percentage of patients in the HR, LR, and P groups who achieved MOAA/S levels 1–4 within 3 min after administration was 85.7%, 58.8%, and 82.9%, respectively. However, the time to recovery from anesthesia after withdrawal of sedatives (7.9 ± 5.7 min), incidence of anterograde amnesia (75%), and adverse effects were not statistically significant among the three groups. These findings suggest that a loading dose of remimazolam 0.1 mg/kg followed by a maintenance infusion of 0–3 mg/kg/h provides adequate sedation for patients under regional anesthesia without increasing adverse reactions.

本研究旨在评估区域麻醉期间使用雷马唑仑进行术中镇静的有效性和安全性。这是一项II期多中心、随机、单盲、平行组、主动对照临床试验(编号:ChiCTR2100054956)。从 2021 年 5 月 6 日至 2021 年 7 月 4 日,患者从中国的 17 家医院随机入组。共纳入 105 名年龄在 18-65 岁之间、在区域麻醉下接受选择性手术的患者。患者接受了不同剂量的镇静剂:每公斤 0.1 毫克瑞马唑仑(HR 组)、每公斤 0.05 毫克瑞马唑仑(LR 组)或每公斤 1.0 毫克丙泊酚(P 组),然后进行维持输注。主要结果指标包括镇静过程中通过改良观察者警觉性评估/镇静量表(MOAA/S)水平(1-4、1-3、2-3、3和2-4)测量的镇静效果(持续时间百分比)和不良反应发生率。结果显示,MOAA/S 1-4 级的持续时间百分比在 HR 组、LR 组和 P 组分别为 100.0 [8.1]%(中位数[四分位距])、89.9 [20.2]%、100.0 [7.7]%。HR、LR 和 P 组患者在用药后 3 分钟内达到 MOAA/S 1-4 级的比例分别为 85.7%、58.8% 和 82.9%。然而,三组患者在停用镇静剂后的麻醉恢复时间(7.9 ± 5.7 分钟)、逆行性遗忘发生率(75%)和不良反应方面均无统计学意义。这些研究结果表明,负荷剂量为 0.1 毫克/千克的瑞马唑仑,然后以 0-3 毫克/千克/小时的剂量输注,可为接受区域麻醉的患者提供充分的镇静效果,同时不会增加不良反应。
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引用次数: 0
The influence of sleep disorders on perioperative neurocognitive disorders among the elderly: A narrative review 睡眠障碍对老年人围手术期神经认知障碍的影响:叙述性综述
Pub Date : 2024-06-08 DOI: 10.1002/ibra.12167
Chao Chen, Rui-Xue Zhai, Xin Lan, Sheng-Feng Yang, Si-Jie Tang, Xing-Long Xiong, Yu-Xin He, Jing-Fang Lin, Jia-Rong Feng, Dong-Xu Chen, Jing Shi

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood–brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

本综述全面评估了老年人围手术期睡眠障碍(SD)和围手术期神经认知障碍(PND)的流行病学、相互作用以及对患者预后的影响。老年人围手术期睡眠障碍(SD)和围手术期神经认知障碍(PND)的发病率之高令人震惊,其中睡眠障碍是导致术后谵妄的重要原因。然而,尽管有大量的临床前数据,但将 SD 与 PND 联系起来的临床证据仍然不足。因此,本研究将重点放在 SD 与 PND 之间的潜在机制上,强调推动 SD 诱发 PND 的潜在机制包括中枢神经炎症失控、血脑屏障破坏、昼夜节律紊乱、神经胶质细胞功能障碍、神经元和突触异常、中枢代谢废物清除受损、肠道微生物组失调、海马氧化应激和大脑网络连接改变。此外,该综述还评估了各种药物和非药物睡眠干预措施在减轻 PND 方面的效果。耳塞、眼罩、恢复昼夜节律、体育锻炼、无创脑刺激、右美托咪定和褪黑激素受体激动剂等策略在降低 PND 发生率方面显示出了疗效。其他改善睡眠的药物(例如奥曲肽受体拮抗剂)和方法(例如失眠认知行为疗法)对 PND 的影响尚不清楚。然而,某些用于治疗 SD 的药物(如抗抑郁药和第一代抗组胺药)可能会加重 PND。通过提供有价值的见解和参考文献,本综述旨在加强对基于 SD 的老年人 PND 的理解和管理。
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引用次数: 0
Lithocarpus polystachyus Rehd. leaves aqueous extract inhibits learning and memory impairment in Alzheimer's disease rats: Involvement of the SIRT6/NLRP3 signaling pathway 石蒜叶水提取物可抑制阿尔茨海默病大鼠的学习和记忆损伤:SIRT6/NLRP3信号通路的参与
Pub Date : 2024-06-03 DOI: 10.1002/ibra.12164
Wendan Wu, You Yan, Tingting Yi, Yu Wei, Jian-mei Gao, Qihai Gong
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative condition that is influenced by multiple factors along with neuroinflammation and oxidative stress. Our previous study proved that Lithocarpus polystachyus Rehd. aqueous extract (sweet tea aqueous extract, STAE) effectively inhibits hydrogen peroxide‐induced neuronal cell injury. However, it is not clear whether STAE can protect against AD, and its underlying mechanisms are still uncertain. Therefore, the present study was designed to evaluate the possible behavioral and neurochemical effects of STAE on Aβ25‐35‐induced AD rats administered STAE (20, 40, 80 mg/mL) for 14 days. We showed that STAE administration significantly and dose‐dependently ameliorated the cognitive deficits in the AD rat models, assessed in the Morris water maze (MWM) test, Y‐maze test, and novel object recognition (NOR) test. The results of hematoxylin and eosin (H&E) staining and Nissl staining showed that after treatment with STAE, the pathological damage to the hippocampal CA1, CA3, and dentate gyrus (DG) neurons of rats was significantly improved. Furthermore, STAE dose‐dependently inhibited microglia and astrocyte activation in the hippocampus of rats accompanied by increased protein expression of silent mating‐type information regulation 2 homolog 6 (SIRT6) and decreased protein expression of nod‐like receptor thermal protein domain‐associated protein 3 (NLRP3) and its downstream pyroptosis‐related genes after following Aβ25‐35. In summary, our findings indicate that STAE effectively inhibits Aβ25‐35‐induced learning and memory impairment in rats, and the mechanism is, at least partially, related to the regulation of SIRT6/NLRP3 signaling pathway.
阿尔茨海默病(AD)是一种慢性进行性神经退行性疾病,受到神经炎症和氧化应激等多种因素的影响。我们之前的研究证明,甜茶水提取物(Lithocarpus polystachyus Rehd.)能有效抑制过氧化氢诱导的神经细胞损伤。然而,甜茶水提取物是否能预防注意力缺失症尚未明确,其潜在机制也尚不清楚。因此,本研究旨在评估STAE对Aβ25-35诱导的AD大鼠可能产生的行为和神经化学效应。我们的研究表明,在莫里斯水迷宫(MWM)测试、Y-迷宫测试和新物体识别(NOR)测试中,STAE能显著改善AD大鼠模型的认知缺陷,且与剂量相关。苏木精和伊红(H&E)染色及Nissl染色结果表明,STAE治疗后,大鼠海马CA1、CA3和齿状回(DG)神经元的病理损伤明显改善。此外,STAE剂量依赖性地抑制了大鼠海马中小胶质细胞和星形胶质细胞的活化,同时还增加了沉默配子型信息调控2同源物6(SIRT6)的蛋白表达,并降低了Aβ25-35治疗后类结受体热蛋白结构域相关蛋白3(NLRP3)及其下游热变态反应相关基因的蛋白表达。综上所述,我们的研究结果表明,STAE能有效抑制Aβ25-35诱导的大鼠学习和记忆损伤,其机制至少部分与调节SIRT6/NLRP3信号通路有关。
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引用次数: 0
Research progress of neurovascular units involved in ischemic stroke 缺血性中风相关神经血管单元的研究进展
Pub Date : 2024-06-03 DOI: 10.1002/ibra.12166
Yu Yang, Hao Tong, Zhuo‐Fan Ye, Zu‐Cai Xu, Tao Tao
Ischemic stroke is the most prevalent cerebrovascular disorder in the clinical setting. It results in associated neurological abnormalities due to a variety of factors, including disruption of cerebral arterial blood flow, hypoxia, and ischemic necrosis of local brain tissues. The neurovascular unit (NVU) is a dynamic structural complex that consists of neurons, glial cells, pericytes, vascular endothelial cells, and the extracellular matrix. Many cells work together to preserve the integrity of the central nervous system (CNS) under physiological conditions. However, following ischemic stroke, NVU homeostasis is disrupted along with the development of tissue ischemia and hypoxia, as well as impaired interactions between various components of the NVU. Collectively, the changes result in increased blood–brain barrier permeability, neuronal dysfunction, and functional destruction of nerve conduction bundles, ultimately leading to the clinical manifestation of neurological deficits including motor, cognitive, and speech impairments that hinder the rehabilitation process. In recent years, with continuously expanding research on ischemic cerebrovascular disease, the role of interconnections between different cells in the NVU in ischemic stroke has received increasing attention. To describe new concepts for the prevention and treatment of ischemic cerebrovascular illnesses, this article reviews the interplay between NVU in the pathogenesis of ischemic stroke.
缺血性中风是临床上最常见的脑血管疾病。由于脑动脉血流中断、缺氧和局部脑组织缺血性坏死等多种因素,导致相关神经系统异常。神经血管单元(NVU)是一个动态的结构复合体,由神经元、神经胶质细胞、周细胞、血管内皮细胞和细胞外基质组成。在生理条件下,许多细胞共同维护中枢神经系统(CNS)的完整性。然而,缺血性中风后,随着组织缺血和缺氧的发展,以及 NVU 各成分之间相互作用的受损,NVU 的平衡被破坏。这些变化共同导致血脑屏障通透性增加、神经元功能障碍和神经传导束的功能性破坏,最终导致神经功能缺损的临床表现,包括运动、认知和语言障碍,阻碍康复进程。近年来,随着对缺血性脑血管病研究的不断深入,缺血性脑卒中中NVU不同细胞间的相互联系作用日益受到关注。为了阐述预防和治疗缺血性脑血管疾病的新概念,本文综述了缺血性中风发病机制中无损伤单元之间的相互作用。
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引用次数: 0
Systemic mechanism of Panax noteginseng saponins in antiaging based on network pharmacology combined with experimental validation 基于网络药理学和实验验证的三七皂苷抗衰老的系统机制
Pub Date : 2024-06-01 DOI: 10.1002/ibra.12165
Yang‐Yang Zhao, Li‐Xia Yang, Shuang‐Yu Que, Lei‐Xing An, Abeer A. Teeti, Shun‐Wu Xiao
This study aims to investigate the systemic mechanism of Panax notoginseng saponins (PNS) in antiaging using network pharmacology combined with experimental validation. String database and Cytoscape3.7.2 were used to perform the protein–protein interaction (PPI) and construct genes network. The key target genes were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the aging‐related genes were verified by reverse‐transcription polymerase chain reaction in SAM‐P/8 mice, and performed molecular docking with the main components of PNS. Moreover, it produced cluster between Hub genes and differential genes. A total of 169 crossover genes were obtained, and the results of GO and KEGG indicated that the antiaging effect of PNS was mediated by apoptosis, cancer, and neurodegeneration and that five of the eight Hub genes had good binding activity with the main components of PNS. In addition, animal experiments reported that MAP2, MAPKK4, RAB6A, and Sortilin‐1 have different levels of expression in the brain tissues of aging mice, and bind well docking with the main active components of PNS. However, there was no crossover between the 169 PNS intersecting genes and the four differential genes, while they yielded a link from PPI in which MAP2K4 was only linked to AKT1 and CASP3; MAP2 was only linked to AKT1 and CASP3; RAB6A was only linked to AKT1; but Sortlin‐1 did not link to the Hub genes. In summary, the antiaging effect of PNS is associated with the eight Hub genes and four differential genes. All of them consist of a cluster or group that is possibly related to the antiaging effect of PNS.
本研究旨在利用网络药理学结合实验验证的方法研究三七皂苷(PNS)抗衰老的系统机制。研究使用String数据库和Cytoscape3.7.2进行蛋白相互作用(PPI),构建基因网络。利用基因本体(GO)和京都基因组百科全书(KEGG)分析了关键靶基因。然后,通过反转录聚合酶链反应在 SAM-P/8 小鼠中验证了衰老相关基因,并与 PNS 的主要成分进行了分子对接。此外,它还产生了枢纽基因和差异基因之间的聚类。GO和KEGG的结果表明,PNS的抗衰老作用是由细胞凋亡、癌症和神经变性介导的,8个Hub基因中有5个与PNS的主要成分具有良好的结合活性。此外,动物实验报告显示,MAP2、MAPKK4、RAB6A 和 Sortilin-1 在衰老小鼠的脑组织中有不同程度的表达,并与 PNS 的主要活性成分有良好的对接结合。然而,169个PNS交叉基因与4个差异基因之间没有交叉,而它们从PPI中产生了联系,其中MAP2K4只与AKT1和CASP3有联系;MAP2只与AKT1和CASP3有联系;RAB6A只与AKT1有联系;但Sortilin-1与枢纽基因没有联系。总之,PNS 的抗衰老作用与 8 个 Hub 基因和 4 个差异基因有关。所有这些基因都组成了一个可能与 PNS 的抗衰老效应有关的基因簇或基因群。
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引用次数: 0
Green silver nanoparticles: Prospective nanotools against neurodegenerative cell line model 绿色银纳米粒子:针对神经退行性细胞系模型的前瞻性纳米工具
Pub Date : 2024-05-23 DOI: 10.1002/ibra.12157
Valeria De Matteis, Simona Martano, Paolo Pellegrino, Chiara Ingrosso, Daniele Costa, Stefano Mazzotta, Jose L. Toca-Herrera, Rosaria Rinaldi, Mariafrancesca Cascione

Neurodegenerative diseases represent an increasingly burdensome challenge of the past decade, primarily driven by the global aging of the population. Ongoing efforts focus on implementing diverse strategies to mitigate the adverse effects of neurodegeneration, with the goal of decelerating the pathology progression. Notably, in recent years, it has emerged that the use of nanoparticles (NPs), particularly those obtained through green chemical processes, could constitute a promising therapeutic approach. Green NPs, exclusively sourced from phytochemicals, are deemed safer compared to NPs synthetized through conventional chemical route. In this study, the effects of green chemistry-derived silver NPs (AgNPs) were assessed in neuroblastoma cells, SHSY-5Y, which are considered a pivotal model for investigating neurodegenerative diseases. Specifically, we used two different concentrations (0.5 and 1 µM) of AgNPs and two time points (24 and 48 h) to evaluate the impact on neuroblastoma cells by observing viability reduction and intracellular calcium production, especially using 1 µM at 48 h. Furthermore, investigation using atomic force microscopy (AFM) unveiled an alteration in Young's modulus due to the reorganization of cortical actin following exposure to green AgNPs. This evidence was further corroborated by confocal microscopy acquisitions as well as coherency and density analyses on actin fibers. Our in vitro findings suggest the potential efficacy of green AgNPs against neurodegeneration; therefore, further in vivo studies are imperative to optimize possible therapeutic protocols.

神经退行性疾病是近十年来日益严峻的挑战,其主要原因是全球人口老龄化。目前的工作重点是实施各种策略来减轻神经退行性疾病的不利影响,目的是减缓病理进展。值得注意的是,近年来,人们发现使用纳米粒子(NPs),尤其是通过绿色化学工艺获得的纳米粒子,可以成为一种前景广阔的治疗方法。与通过传统化学途径合成的纳米粒子相比,完全来自植物化学物质的绿色纳米粒子被认为更安全。在本研究中,我们评估了源于绿色化学的银纳米粒子(AgNPs)在神经母细胞瘤细胞 SHSY-5Y 中的作用,SHSY-5Y 被认为是研究神经退行性疾病的重要模型。具体来说,我们使用了两种不同浓度(0.5 和 1 µM)的 AgNPs 和两个时间点(24 和 48 小时)来评估其对神经母细胞瘤细胞的影响,观察其存活率的降低和细胞内钙的产生,尤其是在 48 小时内使用 1 µM。共聚焦显微镜采集以及肌动蛋白纤维的一致性和密度分析进一步证实了这一点。我们的体外研究结果表明,绿色银纳米粒子对神经退行性病变具有潜在疗效;因此,必须进一步开展体内研究,以优化可能的治疗方案。
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引用次数: 0
Endothelial cellular senescence and tau accumulation: An interplay full of opportunities? 内皮细胞衰老和 tau 累积:充满机遇的相互作用?
Pub Date : 2024-05-09 DOI: 10.1002/ibra.12154
Doriana Oliveri, Giorgia Moschetti, Anna Griego, Edoardo Scarpa

Recent research has shown that tau protein can be passed to neighboring cells, leading to cellular senescence in the endothelial cells present in the central nervous system (CNS). This discovery could potentially open new doors for testing novel therapeutic compounds that specifically target senescent cells (senolytics) or for identifying new biomarkers that can enable early detection of tauopathies and dementia.

内皮细胞衰老:治疗tau病的契机。最新研究表明,tau 蛋白可传递给邻近细胞,导致中枢神经系统(CNS)内皮细胞衰老。这一发现有可能为测试专门针对衰老细胞的新型治疗化合物(衰老分解剂)或确定新的生物标志物打开新的大门,这些生物标志物可用于早期检测tau病症和痴呆症。BBB,血脑屏障.图片
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引用次数: 0
Accuracy and efficacy of ultrasound-guided puncture (vs. computed tomography-guided) in cervical medial branch blocks for cervicogenic pain: A randomized controlled study 超声引导下穿刺(与计算机断层扫描引导下)治疗颈椎内侧支阻滞治疗颈源性疼痛的准确性和有效性:随机对照研究
Pub Date : 2024-03-17 DOI: 10.1002/ibra.12151
Jie Tian, Xin-Yan Li, Yan Yin, Nan Zhao, Hong Xiao, Hui Liu

Cervical medial branch block (CMBB) has been recognized as an effective treatment for cervicogenic pain. Previous studies mostly used ultrasound-guided out-of-plane puncture for CMBB, while this prospective study was designed to investigate the efficacy of ultrasound-guided in-plane puncture, specifically focusing on the new target of CMBB for cervical pain. This study includes two parts: the accuracy study (N = 15, CMBB was completed by ultrasound and confirmed by computed tomography [CT], in which a good distribution percentage of the analgesic solution was observed) and the efficacy study (N = 40, CMBB was completed by ultrasound or CT, while the proportion of pain relief (numerical rating scale) decrease by more than 50% postoperatively was analyzed). The results showed that the good distribution percentage of the analgesic solution was 97.8%. Furthermore, in the early period (30 min and 2 h postoperatively), the proportion of patients with pain relief was lower in the ultrasound group than that in the CT group, especially at 2 h postoperatively (52% vs. 94%). However, at 24 h postoperatively and later, the proportion of patients with pain relief gradually stabilized to about 60%–70%, and lasted for about 2 weeks to 1 month. Therefore, the new target for CMBB, guided by ultrasound in-plane, offers high visibility and accuracy. A single CMBB performed under ultrasound guidance resulted in pain relief comparable to that of a CT-guided procedure (1 day to 1 month postoperatively). This study indicated that CMBB guided by ultrasound in-plane could be regarded as a promising approach for treatment of cervicogenic pain.

颈内侧支阻滞(CMBB)已被认为是治疗颈源性疼痛的有效方法。以往的研究多采用超声引导下平面外穿刺进行 CMBB,而本前瞻性研究旨在探讨超声引导下平面内穿刺的疗效,特别关注 CMBB 治疗颈椎痛的新靶点。本研究包括两部分:准确性研究(15 人,通过超声完成 CMBB,并通过计算机断层扫描[CT]确认,其中观察到镇痛液的良好分布比例)和有效性研究(40 人,通过超声或 CT 完成 CMBB,同时分析术后疼痛缓解(数字评分量表)减少 50%以上的比例)。结果显示,镇痛液的良好分布率为 97.8%。此外,在早期(术后 30 分钟和 2 小时),超声组患者疼痛缓解的比例低于 CT 组,尤其是在术后 2 小时(52% 对 94%)。但在术后 24 小时及以后,疼痛缓解的患者比例逐渐稳定在 60%-70% 左右,并持续约 2 周至 1 个月。因此,在平面内超声引导下的 CMBB 新靶点具有较高的可视性和准确性。在超声引导下进行单次 CMBB 的疼痛缓解效果与 CT 引导下的手术相当(术后 1 天至 1 个月)。这项研究表明,平面内超声引导下的 CMBB 是一种治疗颈源性疼痛的有效方法。
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引用次数: 0
Role and limitation of cell therapy in treating neurological diseases 细胞疗法在治疗神经系统疾病中的作用和局限性
Pub Date : 2024-03-12 DOI: 10.1002/ibra.12152
Yu-Qi Li, Peng-Fei Li, Qian Tao, Issam J. A. Abuqeis, Yan-Bin Xiyang

The central role of the brain in governing systemic functions within human physiology underscores its paramount significance as the focal point of physiological regulation. The brain, a highly sophisticated organ, orchestrates a diverse array of physiological processes encompassing motor control, sensory perception, cognition, emotion, and the regulation of vital functions, such as heartbeat, respiration, and hormonal equilibrium. A notable attribute of neurological diseases manifests as the depletion of neurons and the occurrence of tissue necrosis subsequent to injury. The transplantation of neural stem cells (NSCs) into the brain exhibits the potential for the replacement of lost neurons and the reconstruction of neural circuits. Furthermore, the transplantation of other types of cells in alternative locations can secrete nutritional factors that indirectly contribute to the restoration of nervous system equilibrium and the mitigation of neural inflammation. This review summarized a comprehensive investigation into the role of NSCs, hematopoietic stem cells, mesenchymal stem cells, and support cells like astrocytes and microglia in alleviating neurological deficits after cell infusion. Moreover, a thorough assessment was undertaken to discuss extant constraints in cellular transplantation therapies, concurrently delineating indispensable model-based methodologies, specifically on organoids, which were essential for guiding prospective research initiatives in this specialized field.

大脑在调节人体生理系统功能方面发挥着核心作用,这凸显了它作为生理调节焦点的重要意义。大脑作为一个高度精密的器官,协调着各种生理过程,包括运动控制、感官知觉、认知、情感以及对心跳、呼吸和激素平衡等生命功能的调节。神经系统疾病的一个显著特征是神经元耗竭和损伤后组织坏死。将神经干细胞(NSCs)移植到大脑中可替代失去的神经元,重建神经回路。此外,在其他位置移植其他类型的细胞可分泌营养因子,间接促进神经系统平衡的恢复和神经炎症的缓解。这篇综述总结了对NSCs、造血干细胞、间充质干细胞以及星形胶质细胞和小胶质细胞等支持细胞在缓解细胞输注后神经功能缺损方面作用的全面研究。此外,研究人员还进行了全面评估,讨论了细胞移植疗法中的现有限制因素,同时界定了不可或缺的基于模型的方法,特别是关于器官组织的方法,这些方法对于指导这一专业领域的前瞻性研究计划至关重要。
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引用次数: 0
IGF2BP2 modulates autophagy and serves as a prognostic marker in glioma IGF2BP2 可调节自噬,是胶质瘤的预后标志物
Pub Date : 2024-03-11 DOI: 10.1002/ibra.12150
Ning Li, Limei Deng, Yuming Zhang, Xilian Tang, Bingxi Lei, Qingyu Zhang

Glioma, a malignant brain tumor originating from neural glial cells, presents significant treatment challenges. However, the underlying mechanisms of glioma development are not fully understood, and effective targets are lacking. This study provides insights into the role of insulin-like growth factor 2 messenger RNA-binding protein 2 (IGF2BP2) in glioma progression and its therapeutic potential. Our analysis illustrated that elevated IGF2BP2 expression associated with significantly shorter survival among patients with low-grade glioma (LGG) in The Cancer Genome Atlas (TCGA) database. IGF2BP2 depletion led to compromised cell viability, G0/G1 phase arrest, and reduced colony-formation ability. Furthermore, ultrastructural analysis and mCherry-GFP-LC3 reporter assay revealed an increased abundance of autophagosomes upon IGF2BP2 knockdown. Western blot analysis corroborated these findings by showing reduced p62 levels coupled with increased LC3-ІІ/LC3-I ratio upon IGF2BP2 knockdown. A multicolor immunohistochemistry assay demonstrated the positive correlation between IGF2BP2 and p62 expression in glioma patient samples. Additionally, our analysis suggested a link between IGF2BP2 expression and drug-resistant markers in TCGA-LGG samples, and Cell Counting Kit-8 cell viability assay revealed that knockdown of IGF2BP2 sensitized cells to temozolomide treatment. This comprehensive exploration unveils the role of IGF2BP2 in glioma progression, shedding light on autophagy modulation and chemosensitization strategies for glioma therapy.

胶质瘤是一种源自神经胶质细胞的恶性脑肿瘤,给治疗带来了巨大挑战。然而,胶质瘤发展的内在机制尚未完全明了,也缺乏有效的靶点。本研究深入探讨了胰岛素样生长因子2信使RNA结合蛋白2(IGF2BP2)在胶质瘤发展过程中的作用及其治疗潜力。我们的分析表明,在癌症基因组图谱(TCGA)数据库中,IGF2BP2表达升高与低级别胶质瘤(LGG)患者的生存期明显缩短有关。IGF2BP2消耗会导致细胞活力受损、G0/G1期停滞和集落形成能力下降。此外,超微结构分析和mCherry-GFP-LC3报告检测显示,IGF2BP2敲除后自噬体的丰度增加。Western 印迹分析证实了这些发现,显示 IGF2BP2 敲除后 p62 水平降低,LC3-ІІ/LC3-I 比率增加。多色免疫组化分析表明,在胶质瘤患者样本中,IGF2BP2 和 p62 的表达呈正相关。此外,我们的分析表明,在TCGA-LGG样本中,IGF2BP2的表达与耐药标记物之间存在联系,细胞计数试剂盒-8细胞活力测定显示,敲除IGF2BP2可使细胞对替莫唑胺治疗敏感。这一全面探索揭示了IGF2BP2在胶质瘤进展中的作用,为胶质瘤治疗中的自噬调节和化疗增敏策略提供了启示。
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