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Analysis of Concentrations of Monomethyl Fumarate in Patients with Multiple Sclerosis: Result from Routine Health Care 多发性硬化症患者富马酸单甲酯浓度分析:常规医疗保健的结果。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273302279240529104919
Zuzana Krska Kusnirikova, Ivana Kacirova, Veronika Pesakova, Pavel Hradilek, Hana Brozmanova, Milan Grundmann

Background: Dimethyl fumarate is used to treat patients with relapsing-remitting multiple sclerosis. After ingestion, it is rapidly hydrolyzed to the active primary metabolite monomethyl fumarate.

Objective: The main objective of our study was to analyze serum concentrations of monomethyl fumarate during routine health care in patients with multiple sclerosis treated with a fixed dose of dimethyl fumarate.

Methods: In the pilot cross-sectional study, data from 42 patients treated with dimethyl fumarate at a dose of 240 mg twice daily were collected. Concentrations of the active metabolite monomethyl fumarate were determined at 1-8 h (median, 3 h) or 10-14 h (median, 13 h) after taking the dose. The relationship between monomethyl fumarate concentrations and absolute lymphocyte count was evaluated.

Results: Concentrations of monomethyl fumarate ranged from 2.5-3177.9 μg/L, with most concentrations being undetectable approximately 10 hours after administration. In the 1-8 h (median, 3 h) post-dose subgroup, the concentration/dose ratio ranged widely from 0.04-6.62. The median concentration of monomethyl fumarate in the group with the absolute lymphocyte count <0.8 x 10^9/l was more than four times higher than in the group with the absolute lymphocyte count ≥0.8 x 10^9/l (median 440.1 μg/L versus 98.4 μg/L).

Conclusion: The wide interindividual variability in monomethyl fumarate pharmacokinetics could contribute to the differential response to dimethyl fumarate in multiple sclerosis patients. A nonsignificant but noticeable trend was observed in the relationship of higher serum monomethyl fumarate concentrations to absolute lymphocyte counts.

背景:富马酸二甲酯用于治疗复发-缓解型多发性硬化症患者。富马酸二甲酯摄入后会迅速水解为活性初级代谢物富马酸单甲酯:我们研究的主要目的是分析接受固定剂量富马酸二甲酯治疗的多发性硬化症患者在日常保健过程中血清中富马酸单甲酯的浓度:在这项试验性横断面研究中,收集了42名接受富马酸二甲酯治疗的患者的数据,治疗剂量为240毫克,每天两次。在服药后 1-8 小时(中位数为 3 小时)或 10-14 小时(中位数为 13 小时)测定活性代谢物富马酸单甲酯的浓度。评估了富马酸单甲酯浓度与淋巴细胞绝对计数之间的关系:结果:富马酸单甲酯的浓度范围为 2.5-3177.9 μg/L,大多数浓度在服药后 10 小时左右检测不到。在给药后 1-8 小时(中位数为 3 小时)的亚组中,浓度/剂量比范围很广,从 0.04-6.62 不等。在淋巴细胞绝对计数组中,富马酸单甲酯的中位浓度为 0.04-6.62:富马酸单甲酯药代动力学的个体间差异很大,这可能是多发性硬化症患者对富马酸二甲酯反应不同的原因之一。在较高的血清富马酸单甲酯浓度与绝对淋巴细胞计数的关系中,观察到了一种不显著但明显的趋势。
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引用次数: 0
Food, Dietary Supplements and Nutraceuticals in Aging and Neurodegenerative Diseases. 老龄化和神经退行性疾病中的食品、膳食补充剂和保健品。
Pub Date : 2024-01-01 DOI: 10.2174/187152732305231202011902
Fabiola De Marchi, Giacomo Tondo
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引用次数: 0
Anti-seizure Medications: Challenges and Opportunities. 抗癫痫药物:挑战与机遇。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273275793231030060833
Neha Tandon, Milica Radosavljevic, Danijela Vucevic, Miroslav Radenkovic, Jasna Jancic, Janko Samardzic

Epilepsy is a chronic neurological condition characterized by unprovoked, recurrent seizures. There are several types of epilepsy, and the cause of the condition can vary. Some cases of epilepsy have a genetic component, while others may be caused by brain injuries, infections, or other underlying conditions. Treatment for epilepsy typically involves anti-seizure medications (ASMs), although different approaches, such as surgery or a special diet, may be considered in specific cases. The treatment aims to effectively manage and potentially eliminate seizures while minimizing any accompanying side effects. Many different ASMs are available, and the choice of medication depends on several factors, including the type of seizures, the patient's age, general health, and potential drug interactions. For the treatment of epilepsy, there have been significant advancements in recent decades, which have led to the approval of many different ASMs. Newer ASMs offer a broader range of mechanisms of action, improved tolerability profiles, and reduced drug interactions compared to older drugs. This review aims to discuss the pharmacological characteristics, clinical applications, effectiveness, and safety of ASMs, with a particular emphasis on various age groups, especially children. Moreover, this review seeks to provide a comprehensive understanding of ASM therapy for epilepsy management, assisting physicians in selecting suitable ASMs for their patients.

癫痫是一种慢性神经系统疾病,其特点是无诱因、反复发作。癫痫有多种类型,病因也各不相同。有些癫痫有遗传因素,有些则可能由脑损伤、感染或其他潜在疾病引起。癫痫的治疗通常包括抗癫痫药物(ASMs),但在特殊情况下也可能考虑不同的方法,如手术或特殊饮食。治疗的目的是有效控制并可能消除癫痫发作,同时尽量减少任何伴随的副作用。有许多不同的 ASM 可供选择,药物的选择取决于几个因素,包括癫痫发作的类型、患者的年龄、总体健康状况和潜在的药物相互作用。在治疗癫痫方面,近几十年来取得了重大进展,许多不同的 ASMs 因此获得批准。与老药相比,新的 ASM 具有更广泛的作用机制、更好的耐受性和更少的药物相互作用。本综述旨在讨论 ASMs 的药理特征、临床应用、有效性和安全性,尤其侧重于各年龄组,特别是儿童。此外,本综述还旨在全面介绍 ASM 治疗癫痫的方法,帮助医生为患者选择合适的 ASM。
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引用次数: 0
LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping. LRRK2;在帕金森病和溃疡性结肠炎治疗中的沟通作用重叠。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273270874231205050727
Naser-Aldin Lashgari, Nazanin Momeni Roudsari, Amirhossein Niknejad, Hedieh Sadat Shamsnia, Maryam Shayan, Leila Mohaghegh Shalmani, Saeideh Momtaz, Nima Rezaei, Amir Hossein Abdolghaffari

Background: Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles.

Objective: Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments.

Method: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022.

Result: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment.

Conclusion: Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

背景:胃肠道炎症与帕金森病(PD)发病机制和运动的关系逐渐浮出水面。炎症涉及帕金森病和炎症性肠病(IBD)的病因。富亮氨酸复性激酶 2(LRRK2)的转变是 IBD 和 PD 的最佳遗传支持因素之一。据报道,在IBD患者受刺激的结肠组织和不规则PD患者的外周无损细胞中,LRRK2水平升高;因此,人们认为LRRK2引导炎症循环:LRRK2自被揭示以来,一直与神经元密切相关,尽管各种证据都证实LRRK2在无创细胞中具有深远的沟通作用。因此,LRRK2可能位于胃部炎症的交界处,IBD中较高的LRRK2水平可能是不一致的PD风险扩大的生物标志物,或者可能在增加PD风险的传染性疾病中解决一个可管理的有用目标。在此,我们讨论了PD和IBD如何共同覆盖聚集,特别是关于LRRK2和目前的抑制剂,这可能是正在进行的治疗中的一个有用的目标:从谷歌学术、PubMed、Scopus和Cochrane图书馆1990年至2022年12月间发表的研究中获取英文数据:结果:LRRK2通路抑制剂可被视为治疗IBD和PD的新型治疗方法:IBD和PD的病理生理学涉及共同的介质和通路,它们主要与炎症情况相关。这些疾病可用于进一步的临床研究。
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引用次数: 0
Vasospasm in Pediatric Subarachnoid Hemorrhage. 小儿蛛网膜下腔出血的血管痉挛。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273274147231104160152
Ioannis Mavridis, Efstratios-Stylianos Pyrgelis, Eleni Agapiou, Jeries Assi

Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.

脑血管痉挛(CV)是蛛网膜下腔出血(SAH)的常见严重并发症,SAH是一种在儿童中罕见的严重颅内出血类型。本文的目的是回顾目前关于这种潜在的破坏性并发症的文献。CV可能是无症状的,与成人相比,在儿童中较少见。包括炎症在内的一些分子现象有助于其病理生理。小儿侧支循环好,脑血流量高是保护因素。当临床表现明显时,CV可能表现为儿童神经状态或生命体征的改变。CV可通过脑血管造影诊断,如计算机断层血管造影、磁共振血管造影、数字减影血管造影、经颅多普勒超声、计算机断层灌注等。动脉直径减小< 50%证实了诊断。除了一般的支持措施和SAH的病因治疗外,心血管治疗的选择包括钙通道阻滞剂和神经介入方法,如动脉内血管扩张剂和球囊血管成形术。儿童的长期结果通常是有利的。
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引用次数: 0
Memory Reflections of the Microbiota-Gut and Oligodendrocyte Axis. 微生物群肠道和少突胶质细胞轴的记忆反射。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273256132230921103333
Suman Kumar Ray, Sukhes Mukherjee

Memory is the persisting consequence of cognitive activities instigated by and engrossed on exterior information from the environment and commenced by an intensive on internal mental representations. Establishing a gut-brain axis (GBA) in health and disease has recently brought the gut, the main portal of communication with the external environment, to the forefront of this interaction. Dietary stimuli have long been linked to brain development, behavioral responses, and memory reflections. Vagus nerve, immune system, bacterial metabolites and products are just a few of the linkages that make up the GBA, a bidirectional arrangement of signaling pathways that connects the neurological system with the gastrointestinal tract. GBA involves two-way communication between central and enteric neural systems, connecting the brain's affective and cognitive regions to peripheral activities of the intestine. Recent scientific progress has highlighted the significance of gut microbiota in affecting these relationships. By controlling myelination at the prefrontal cortex, a crucial area for multifaceted cognitive behavior forecast and decision-making, this axis influences social behavior, including memory reflections. Humans may experience late myelination of the prefrontal cortex's axonal projections into the third decade of life, making it vulnerable to outside factors like microbial metabolites. It has been demonstrated that changes in the gut microbiome can change the microbial metabolome's composition, impacting highly permeable bioactive chemicals like p-cresol that may hinder oligodendrocyte differentiation. This review will discuss the memory reflections of the microbiota-gut and oligodendrocyte axis. Adopting this concept should encourage a new arena of thinking that recognizes the intricate central and periphery dynamics influencing behavior and uses that knowledge to develop novel therapies and interventions for maladjusted memory and learning systems.

记忆是由来自环境的外部信息激发和吸引的认知活动的持续结果,并由密集的内部心理表征开始。在健康和疾病中建立肠脑轴(GBA)最近将肠道——与外部环境沟通的主要门户——带到了这种互动的前沿。长期以来,饮食刺激与大脑发育、行为反应和记忆反射有关。迷走神经、免疫系统、细菌代谢产物和产物只是构成GBA的几个环节,GBA是连接神经系统和胃肠道的信号通路的双向排列。GBA涉及中枢和肠道神经系统之间的双向交流,将大脑的情感和认知区域与肠道的外围活动联系起来。最近的科学进展突出了肠道微生物群在影响这些关系方面的重要性。通过控制前额叶皮层的髓鞘形成,这个轴影响社会行为,包括记忆反射。前额叶皮层是多方面认知行为预测和决策的关键区域。人类在生命的第三个十年可能会经历前额叶皮层轴突投射的髓鞘形成晚期,使其容易受到微生物代谢产物等外部因素的影响。已经证明,肠道微生物组的变化可以改变微生物代谢组的组成,影响对甲酚等高渗透性生物活性化学物质,这些化学物质可能阻碍少突胶质细胞的分化。这篇综述将讨论微生物群肠道和少突胶质细胞轴的记忆反射。采用这一概念应该鼓励建立一个新的思维领域,认识到影响行为的复杂的中心和外围动态,并利用这些知识为适应不良的记忆和学习系统开发新的疗法和干预措施。
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引用次数: 0
Intrathecal Baclofen Infusion-Botulinum Toxin Combined Treatment Efficacy in the Management of Spasticity due to Cerebral Palsy. 鞘内注射巴氯芬-肉毒杆菌毒素联合疗法在治疗脑瘫所致痉挛症中的疗效
Pub Date : 2024-01-01 DOI: 10.2174/0118715273250973230919121808
Riccardo Marvulli, Giuseppa Lagioia, Giancarlo Ianieri, Lucrezia Dell'Olio, Alessandra Zonno, Mariagrazia Riccardi, Rosa Bianca Sinisi, Laura Belinda Rizzo, Giacomo Farì, Marisa Megna, Maurizio Ranieri

Background: Cerebral Palsy (CP) is a group of permanent, but not unchanging, disorders of movement and/or posture and motor function, which are due to a non-progressive interference, lesion, or abnormality of the developing/immature brain. One clinical presentation is muscle spasticity, which leads to a significant impact on the individual's functionality and quality of life. Spasticity treatment is multidisciplinary and includes pharmacological and physical intervention; intrathecal baclofen shows a positive effect in severe spasticity and suboptimal response to oral drugs, while local injection of Botulinum toxin type A (BTXA) improves muscle tone, motion and pain.

Objective: The aim of this study was to evaluate the efficacy of the combined intrathecal baclofen infusion (ITB) - botulinum toxin treatment in the management of spasticity in CP.

Methods: 8 patients with spastic tetraparesis were enrolled. All patients were treated with intrathecal Baclofen; in lower limbs, no spastic symptoms appeared, while marked spasticity was noted in upper limbs. We injected the right and left Biceps Brachial (BB) and Flexor Digitorum Superficialis (FDS) muscles with botulinum toxin type A. All patients underwent Myometric measurement, Ashworth Scale, Numerical Rating Scale, and Visual Analogic Scale evaluation before infiltration (T0), 30 days after injection (T1), 60 days after injection (T2), and 90 days after treatment (T3).

Results: All data demonstrated an improvement in spasticity, pain, quality of life, and self-care during the study, with p < 0.05. No side effects appeared.

Conclusion: This study demonstrated the efficacy and safety of intrathecal baclofen infusion and botulinum toxin combined treatment in the management of spasticity, pain, quality of life, and selfcare in CP patients.

背景:脑性瘫痪(CP)是一组永久性但并非一成不变的运动和/或姿势和运动功能障碍,是由于发育中/未成熟的大脑受到非进行性干扰、病变或异常所致。其中一种临床表现是肌肉痉挛,这对患者的功能和生活质量造成了极大的影响。痉挛的治疗是多学科的,包括药物和物理干预;鞘内注射巴氯芬对严重痉挛和口服药物反应不佳的患者有积极作用,而局部注射 A 型肉毒杆菌毒素(BTXA)可改善肌张力、运动和疼痛:本研究旨在评估鞘内巴氯芬输注(ITB)-肉毒杆菌毒素联合疗法在治疗痉挛性四肢瘫中的疗效。所有患者均接受了鞘内注射巴氯芬治疗;下肢未出现痉挛症状,而上肢出现明显痉挛。所有患者在注射前(T0)、注射后 30 天(T1)、注射后 60 天(T2)和治疗后 90 天(T3)分别接受了肌肉测量、阿什沃斯量表、数字评定量表和视觉模拟量表评估:所有数据均显示,研究期间痉挛、疼痛、生活质量和自理能力均有所改善,P < 0.05。无副作用出现:本研究证明了鞘内注射巴氯芬和肉毒杆菌毒素联合治疗在治疗 CP 患者痉挛、疼痛、生活质量和自理能力方面的有效性和安全性。
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引用次数: 0
Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF. 孟鲁司特改善东莨菪碱诱导的阿尔茨海默病:对胆碱能神经传递、抗氧化防御系统、神经炎症和BDNF表达的作用。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273258337230925040049
Bhavana Yerraguravagari, Naga Pavani Penchikala, Aravinda Sai Kolusu, Grandhi Sandeep Ganesh, Prasad Konduri, Kumar V S Nemmani, Pavan Kumar Samudrala

Background: Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders.

Objective: This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation.

Methods: Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect.

Results: Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05).

Conclusion: Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels.

背景:阿尔茨海默病(AD)是一种严重的神经退行性疾病,伴有进行性记忆丧失。AD的特征是老年斑块的沉积,主要由β-淀粉样蛋白(Aβ)片段、BDNF下降、胆碱能系统过度活动和神经炎症组成。孟鲁司特(MTK)是一种白三烯受体拮抗剂,在各种神经退行性疾病中表现出惊人的神经保护作用。目的:研究孟鲁司特对东莨菪碱诱导的阿尔茨海默病(AD)大鼠模型的改善作用,并评价其对神经炎症的活性。方法:将30只大鼠分为5组:对照组(生理盐水1 mL/kg,腹腔注射)、孟鲁司特组(10 mg/kg,腹腔注射。)、疾病组(东莨菪碱3 mg/kg,腹腔内注射)、多奈哌齐组(3 mg/kg,静脉注射)、蒙鲁司特治疗组(10 mg/kg,腹腔内)。结果:与对照组相比,东莨菪碱治疗可显著降低学习记忆和胆碱酯酶水平(p<0.01)。此外,氧化应激和淀粉样蛋白-β水平升高与神经炎症增强有关(p<0.05,p<0.01),与正常对照组相比,神经营养因子BDNF也有所下降(p<0.01)。孟鲁司特治疗显著减轻了学习记忆障碍和胆碱酯酶水平。此外,孟鲁司特和标准药物多奈哌齐给药显著抑制了氧化应激标志物(p<0.01)、淀粉样蛋白-β水平,神经炎症介质(p<0.05)并导致BDNF水平显著升高(p<0.05)结论:根据先前的研究,孟鲁司特通过减轻记忆障碍、胆碱酯酶神经传递、氧化应激、淀粉样蛋白-β水平、神经炎症介质和增强BDNF水平,在东莨菪碱诱导的AD动物模型中具有改善作用。
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引用次数: 0
Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets. 作为胶质母细胞瘤 Notch 信号通路关键调控因子的非编码 RNA:诊断、预后和治疗靶点。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273277458231213063147
Seyed Hossein Shahcheraghi, Elmira Roshani Asl, Malihe Lotfi, Jamshid Ayatollahi, Seyed Hossein Khaleghinejad, Alaa A A Aljabali, Hamid A Bakshi, Mohamed El-Tanani, Nitin B Charbe, Ángel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Rohit Goyal, Altijana Hromić-Jahjefendić, Vladimir N Uversky, Marzieh Lotfi, Murtaza M Tambuwala

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

多形性胶质母细胞瘤(GBM)是一种源自星形胶质细胞的高侵袭性脑恶性肿瘤,约占中枢神经系统恶性肿瘤的 30%。尽管手术、化疗和放射性药物等治疗策略取得了进展,但 GBM 患者的预后仍然不容乐观。鉴于 GBM 的侵袭性,有必要确定分子靶点并探索有效的治疗方法来抑制其增殖。Notch 信号通路在细胞稳态中发挥着关键作用,但在 GBM 中却出现失调,导致 MYC、Hes1 和 Hey1 等通路靶基因表达增加,从而促进细胞增殖和分化。最近的研究强调了非编码 RNA(ncRNA)通过在转录后或转录水平靶向关键 mRNA 表达来调节 Notch 信号转导的调控作用。具体来说,各种类型的 ncRNA(包括长非编码 RNA(lncRNA)和 microRNA(miRNA))已被证明可控制多个靶基因,并在很大程度上导致 GBM 癌变。此外,这些 ncRNA 还有望成为 GBM 的预后和预测标志物。本综述旨在总结有关 ncRNA 对 GBM 中 Notch 信号通路的调控作用的最新研究。
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引用次数: 0
The Possible Protective Effect of Taurine on Bisphenol Induced Structural Changes on the Cerebral Cortex of Rats: Histological and Immunohistochemical Study. 牛磺酸对双酚:诱导的大鼠大脑皮层结构变化的可能保护作用:组织学和免疫组化研究。
Pub Date : 2024-01-01 DOI: 10.2174/0118715273280701231227100805
Samah Kandeel, Marwa M Abd-Elsalam, Sherief Abd-Elsalam, Heba Hassan Elkaliny

Introduction: Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions.

Aim: This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods.

Methods: 35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100 mg/kg/day and BPH (100 mg/kg/ three times/week).

Results: BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase- 3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results.

Conclusion: Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.

简介:双酚 A(BPA)是一种化合物,已被用于许多行业,如油漆和牙科密封剂。牛磺酸是一种半必需氨基酸,具有抗氧化、抗炎和抗细胞凋亡的作用。目的:本研究旨在使用组织学和免疫组化方法评估牛磺酸对双酚 A 诱导的大鼠大脑皮层结构变化可能产生的保护作用。材料和方法:35 只 Wistar 大鼠(180-200 gm)分为对照组:10 只;I 组:5 只大鼠接受玉米油(0.5 mL/天);II 组(双酚低剂量;BPAL):5 只大鼠接受低剂量双酚 A(25 mg/kg/三次/周);III 组(双酚高剂量;BPAH):5 只大鼠接受高剂量双酚 A(100 mg/kg/三次/周);IV 组:(BPAL + 牛磺酸):5 只大鼠接受牛磺酸 100 毫克/千克/天和 BPAL(25 毫克/千克/三次/周);第五组:(双酚 AH + 牛磺酸):结果:结果:BPAL和BPAH组大鼠的神经胶质细胞、锥体细胞和神经胶质细胞在H&E染色切片中出现了明显的剂量依赖性组织学变化,GFAP、caspase-3免疫组化反应显著增加,细胞Ki67阳性,有许多有丝分裂。BPAL + 牛磺酸组和 BPAH + 牛磺酸组的上述结果有所改善:牛磺酸可改善双酚 A 诱导的大鼠大脑皮层结构变化。
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CNS & neurological disorders drug targets
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