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Untargeted Metabolomics Revealed that Quercetin Inhibited Ferroptosis by Improving Metabolic Disorder in the Hippocampus of Perimenopausal Depression Model Rats. 非靶向代谢组学揭示槲皮素可通过改善围绝经期抑郁模型大鼠海马区的代谢紊乱抑制铁蛋白沉积
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-08-24 DOI: 10.1007/s12035-024-04445-5
Yali Hou, Heng Qian, Ranqi Yao, Ziran Yu, Jing Wang, Jiaohua Dai, Wenqi Cui, Jian Li, Xiujuan Zhao

Perimenopausal depression is often accompanied by metabolic disorders, which have long-term harmful effects on women's physical and mental health. Quercetin, a kind of phytoestrogen, has anti-inflammatory, antioxidant, and nerve-protective effects, and can regulate various metabolic disorders. This study aims to investigate the effect of quercetin on hippocampal metabolic disorder in perimenopausal depression rat models based on untargeted metabolomics technology. The rat model of perimenopausal depression was established by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Rats with no difference in sucrose preference were randomly divided into four groups (n = 12): sham group, OVX-CUMS group (model group), model plus quercetin group, and model plus 17β-estradiol group. At the end of the experiment, hippocampal tissues were collected for untargeted metabolomics analysis, morphological analysis, and detection of related indicators. Metabolomics identified 23 differential metabolites in the model group, and the pathway analysis discovered hippocampus metabolic abnormalities including the metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, and ubiquinone biosynthesis, accompanied by an increase in oxidative stress, inflammation, and lipid peroxidation indicators. At the same time, the morphological characteristics of ferroptosis occurred in the hippocampus in the model group. These abnormal changes were reversed by treatment with quercetin or 17β-estradiol. Quercetin can improve perimenopausal depression by regulating hippocampal metabolic disorders and reducing hippocampal ferroptosis in rats. These findings provide a new strategy for the use of quercetin in the prevention and treatment of perimenopausal depression.

围绝经期抑郁症往往伴随着新陈代谢紊乱,对妇女的身心健康造成长期有害影响。槲皮素是一种植物雌激素,具有抗炎、抗氧化和保护神经的作用,能调节各种代谢紊乱。本研究旨在基于非靶向代谢组学技术,探讨槲皮素对围绝经期抑郁症大鼠模型海马代谢紊乱的影响。围绝经期抑郁大鼠模型是通过卵巢切除联合慢性不可预测轻度应激(OVX-CUMS)建立的。将蔗糖偏好无差异的大鼠随机分为四组(n = 12):假组、OVX-CUMS 组(模型组)、模型加槲皮素组、模型加 17β-estradiol 组。实验结束后,收集海马组织进行非靶向代谢组学分析、形态学分析和相关指标检测。代谢组学发现模型组有23种差异代谢物,通路分析发现海马代谢异常,包括花生四烯酸代谢、甘油磷脂代谢和泛醌生物合成,并伴有氧化应激、炎症和脂质过氧化指标的增加。同时,模型组的海马出现了铁变态反应的形态特征。槲皮素或17β-雌二醇可逆转这些异常变化。槲皮素可通过调节大鼠海马的代谢紊乱和减少海马铁嗜酸沉着来改善围绝经期抑郁症。这些发现为使用槲皮素预防和治疗围绝经期抑郁症提供了一种新策略。
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引用次数: 0
tubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model. tubg1 体细胞突变体在斑马鱼模型中显示出与管蛋白病相关的神经发育表型
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-08-31 DOI: 10.1007/s12035-024-04448-2
Ozge Cark, Esra Katkat, Ipek Aydogdu, Evin Iscan, Yavuz Oktay, Gunes Ozhan

Development of the multilayered cerebral cortex relies on precise orchestration of neurogenesis, neuronal migration, and differentiation, processes tightly regulated by microtubule dynamics. Mutations in tubulin superfamily genes have been associated with tubulinopathies, encompassing a spectrum of cortical malformations including microcephaly and lissencephaly. Here, we focus on γ-tubulin, a pivotal regulator of microtubule nucleation encoded by TUBG1. We investigate its role in brain development using a zebrafish model with somatic tubg1 mutation, recapitulating features of TUBG1-associated tubulinopathies in patients and mouse disease models. We demonstrate that γ-tubulin deficiency disrupts neurogenesis and brain development, mirroring microcephaly phenotypes. Furthermore, we uncover a novel potential regulatory link between γ-tubulin and canonical Wnt/β-catenin signaling, with γ-tubulin deficiency impairing Wnt activity. Our findings provide insights into the pathogenesis of cortical defects and suggest that γ-tubulin could be a potential target for further research in neurodevelopmental disorders, although challenges such as mode of action, specificity, and potential side effects must be addressed.

多层大脑皮层的发育依赖于神经发生、神经元迁移和分化的精确协调,这些过程受到微管动力学的严格调控。微管蛋白超家族基因突变与微管蛋白病有关,包括小头畸形和无脑畸形等一系列大脑皮层畸形。在这里,我们重点研究γ-微管蛋白,它是由TUBG1编码的微管成核的关键调节因子。我们利用体细胞Tubg1突变的斑马鱼模型研究了它在大脑发育中的作用,再现了患者和小鼠疾病模型中与TUBG1相关的微管蛋白病的特征。我们证明,γ-微管蛋白缺乏会破坏神经发生和大脑发育,反映出小头畸形的表型。此外,我们还发现了γ-tubulin与典型Wnt/β-catenin信号之间潜在的新的调控联系,γ-tubulin缺乏会损害Wnt活性。我们的研究结果为大脑皮层缺陷的发病机制提供了见解,并表明γ-微管蛋白可能是进一步研究神经发育障碍的潜在靶点,但必须解决诸如作用方式、特异性和潜在副作用等难题。
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引用次数: 0
Curculigoside Regulates Apoptosis and Oxidative Stress Against Spinal Cord Injury by Modulating the Nrf-2/NQO-1 Signaling Pathway In Vitro and In Vivo. 莪术苷通过调节体外和体内Nrf-2/NQO-1信号通路调节脊髓损伤的细胞凋亡和氧化应激
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-09-04 DOI: 10.1007/s12035-024-04409-9
Yu Hou, Chaolun Liang, Lili Sui, Yang Li, Kai Wang, Xing Li, Kunrui Zheng, Haitao Su, Dianweng Xie, Dingkun Lin, Da Guo, Le Wang

Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.

脊髓损伤(SCI)是一种严重的神经系统疾病,可导致瘫痪或死亡。脊髓损伤期间的氧化应激是一个关键阶段,会造成广泛的神经细胞损伤和凋亡,从而影响脊髓愈合。因此,SCI 药物治疗的一个主要目标就是减轻氧化应激。莪术苷(CUR)是从莪术(Curculigo orchioides Gaertn)的干燥根茎中提取的一种酚葡萄糖苷,具有神经保护和抗氧化作用。本研究旨在探讨 CUR 是否能有效促进 SCI 后脊髓组织的恢复,并阐明其作用机制。我们采用过氧化氢(H2O2)诱导的 PC12 细胞模型和 SCI 大鼠模型,观察 CUR 对氧化和细胞凋亡的影响。结果表明,CUR能显著降低细胞凋亡相关蛋白(Bax和Caspase-3)、Annexin V/碘化丙啶(PI)和末端脱氧核苷酸转移酶dUTP缺口标记(TUNEL)的表达,同时增加抗凋亡蛋白Bcl-2的表达。此外,CUR 还能有效提高体外抗氧化剂(谷胱甘肽 [GSH])的水平并减少活性氧(ROS)。此外,CUR通过对脊髓损伤大鼠脊髓组织的抗凋亡和抗氧化应激作用,促进了其功能的恢复。这些作用是通过 Nrf2/NQO1 信号通路介导的。因此,我们的研究表明,CUR 可作为一种抗凋亡和抗氧化应激剂,抑制星形胶质细胞活化,促进神经元重建和功能恢复。这些研究结果可能会对SCI治疗方法的开发做出重大贡献,并推动SCI药物治疗领域的发展。
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引用次数: 0
The Use of Identified Hypoxia-related Genes to Generate Models for Predicting the Prognosis of Cerebral Ischemia‒reperfusion Injury and Developing Treatment Strategies. 利用已识别的缺氧相关基因生成模型,以预测脑缺血再灌注损伤的预后并制定治疗策略。
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-09-04 DOI: 10.1007/s12035-024-04433-9
Kaiwen Sun, Hongwei Li, Yang Dong, Lei Cao, Dongpeng Li, Jinghong Li, Manxia Zhang, Dongming Yan, Bo Yang

Cerebral ischemia‒reperfusion injury (CIRI) is a type of secondary brain damage caused by reperfusion after ischemic stroke due to vascular obstruction. In this study, a CIRI diagnostic model was established by identifying hypoxia-related differentially expressed genes (HRDEGs) in patients with CIRI. The ischemia‒reperfusion injury (IRI)-related datasets were downloaded from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ), and hypoxia-related genes in the Gene Cards database were identified. After the datasets were combined, hypoxia-related differentially expressed genes (HRDEGs) expressed in CIRI patients were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the HRDEGs were performed using online tools. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed with the combined gene dataset. CIRI diagnostic models based on HRDEGs were constructed via least absolute shrinkage and selection operator (LASSO) regression analysis and a support vector machine (SVM) algorithm. The efficacy of the 9 identified hub genes for CIRI diagnosis was evaluated via mRNA‒microRNA (miRNA) interaction, mRNA-RNA-binding protein (RBP) network interaction, immune cell infiltration, and receiver operating characteristic (ROC) curve analyses. We then performed logistic regression analysis and constructed logistic regression models based on the expression of the 9 HRDEGs. We next established a nomogram and calibrated the prediction data. Finally, the clinical utility of the constructed logistic regression model was evaluated via decision curve analysis (DCA). This study revealed 9 critical genes with high diagnostic value, offering new insights into the diagnosis and selection of therapeutic targets for patients with CIRI. : Not applicable.

脑缺血再灌注损伤(CIRI)是缺血性脑卒中后因血管阻塞再灌注引起的一种继发性脑损伤。本研究通过识别 CIRI 患者体内与缺氧相关的差异表达基因(HRDEGs),建立了 CIRI 诊断模型。研究人员从基因表达总库(GEO)数据库(http://www.ncbi.nlm.nih.gov/geo )下载了与缺血再灌注损伤(IRI)相关的数据集,并在基因卡片数据库中识别了与缺氧相关的基因。合并数据集后,确定了在 CIRI 患者中表达的缺氧相关差异表达基因(HRDEGs)。利用在线工具对 HRDEGs 进行了基因本体(GO)和京都基因组百科全书(KEGG)通路分析。对合并的基因数据集进行了基因组富集分析(GSEA)和基因组变异分析(GSVA)。通过最小绝对收缩和选择算子(LASSO)回归分析和支持向量机(SVM)算法,构建了基于 HRDEGs 的 CIRI 诊断模型。通过mRNA-microRNA (miRNA)相互作用、mRNA-RNA结合蛋白(RBP)网络相互作用、免疫细胞浸润和接收者操作特征曲线(ROC)分析,评估了已确定的9个枢纽基因对CIRI诊断的功效。然后,我们进行了逻辑回归分析,并根据 9 种 HRDEGs 的表达构建了逻辑回归模型。接下来,我们建立了一个提名图,并对预测数据进行了校准。最后,我们通过决策曲线分析(DCA)评估了所建逻辑回归模型的临床实用性。这项研究揭示了 9 个具有高诊断价值的关键基因,为 CIRI 患者的诊断和治疗目标的选择提供了新的见解。:不适用。
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引用次数: 0
Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective. 精神分裂症患者血清外泌体脂质代谢失调:从生物标志物角度看精神分裂症
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-09-23 DOI: 10.1007/s12035-024-04477-x
Chen-Xi Xu, Wei Huang, Xiao-Jie Shi, Yang Du, Jia-Quan Liang, Xuan Fang, He-Yuan Chen, Yong Cheng

Exosomes, crucial extracellular vesicles, have emerged as potential biomarkers for neurological conditions, including schizophrenia (SCZ). However, the exploration of exosomal lipids in the context of SCZ remains scarce, necessitating in-depth investigation. Leveraging ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), this study aimed to characterize the lipidomic profile of serum exosomes from SCZ patients, assessing their potential as novel biomarkers for SCZ diagnosis through absolute quantitative lipidomics. Our comprehensive lipidomic analysis unveiled 39 serum exosomal lipids that were differentially expressed between SCZ patients (n = 20) and healthy controls (HC, n = 20). These findings revealed a profound dysregulation in lipid metabolism pathways, notably in sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. Among these, seven exosomal lipids stood out for their diagnostic potential, exhibiting remarkable ability to differentiate SCZ patients from HCs with an unparalleled classification performance, evidenced by an area under the curve (AUC) of 0.94 (95% CI, 0.82-1.00). These lipids included specific ceramides and phosphoethanolamines, pointing to a distinct lipid metabolic fingerprint associated with SCZ. Furthermore, bioinformatic analyses reinforced the pivotal involvement of these lipids in SCZ-related lipid metabolic processes, suggesting their integral role in the disorder's pathophysiology. This study significantly advances our understanding of SCZ by pinpointing dysregulated exosomal lipid metabolism as a key factor in its pathology. The identified serum exosome-derived lipids emerge as compelling biomarkers for SCZ diagnosis, offering a promising avenue towards the development of objective and reliable diagnostic tools.

外泌体是一种重要的细胞外囊泡,已成为包括精神分裂症(SCZ)在内的神经系统疾病的潜在生物标记物。然而,对外泌体脂质在精神分裂症(SCZ)方面的研究仍然很少,因此有必要进行深入研究。利用超高效液相色谱-串联质谱(UPLC-MS/MS)技术,本研究旨在表征SCZ患者血清外泌体的脂质组学特征,通过绝对定量脂质组学评估其作为诊断SCZ的新型生物标记物的潜力。我们的综合脂质组学分析发现,39种血清外泌体脂质在SCZ患者(20人)和健康对照组(20人)之间存在差异表达。这些发现揭示了脂质代谢途径的严重失调,尤其是在鞘脂代谢、甘油磷脂代谢和亚油酸代谢方面。在这些脂质中,有七种外泌体脂质具有突出的诊断潜力,它们在区分SCZ患者和HC患者方面表现出了无与伦比的分类能力,其曲线下面积(AUC)为0.94(95% CI,0.82-1.00)。这些脂质包括特定的神经酰胺和磷脂酰乙醇胺,显示出与 SCZ 相关的独特脂质代谢指纹。此外,生物信息学分析进一步证实了这些脂质在 SCZ 相关脂质代谢过程中的关键作用,表明它们在该疾病的病理生理学中扮演着不可或缺的角色。这项研究指出,外泌体脂质代谢失调是SCZ病理的一个关键因素,从而极大地推动了我们对SCZ的了解。经鉴定的血清外泌体脂质可作为诊断SCZ的重要生物标记物,为开发客观可靠的诊断工具提供了一条前景广阔的途径。
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引用次数: 0
Antioxidant Effect of Naringin Demonstrated Through a Bayes' Theorem Driven Multidisciplinary Approach Reveals its Prophylactic Potential as a Dietary Supplement for Ischemic Stroke. 贝叶斯定理驱动的多学科方法证明柚皮苷的抗氧化作用,揭示其作为缺血性中风膳食补充剂的预防潜力
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-10-01 DOI: 10.1007/s12035-024-04525-6
Manju Babu, Rajas M Rao, Anju Babu, Jenat Pazheparambil Jerom, Anaekshi Gogoi, Nikhil Singh, Meenakshi Seshadri, Animikh Ray, Bhaskara P Shelley, Arnab Datta

Naringin (NAR), a flavanone glycoside, occurs widely in citrus fruits, vegetables, and alcoholic beverages. Despite evidence of the neuroprotective effects of NAR on animal models of ischemic stroke, brain cell-type-specific data about the antioxidant efficacy of NAR and possible protein targets of such beneficial effects are limited. Here, we demonstrate the brain cell type-specific prophylactic role of NAR, an FDA-listed food additive, in an in vitro oxygen-glucose deprivation (OGD) model of cerebral ischemia using MTT and DCFDA assays. Using Bayes' theorem-based predictive model, we first ranked the top-10 protein targets (ALDH2, ACAT1, CTSB, FASN, LDHA, PTGS1, CTSD, LGALS1, TARDBP, and CDK1) from a curated list of 289 NAR-interacting proteins in neurons that might be mediating its antioxidant effect in the OGD model. When preincubated with NAR for 2 days, N2a and CTX-TNA2 cells could withstand up to 8 h of OGD without a noticeable decrease in cell viability. This cerebroprotective effect is partly mediated by reducing intracellular ROS production in the above two brain cell types. The antioxidant effect of NAR was comparable with the equimolar (50 µM) concentration of clinically used ROS-scavenger and neuroprotective edaravone. Molecular docking of NAR with the top-10 protein targets from Bayes' analysis showed the lowest binding energy for CDK1 (- 8.8 kcal/M). Molecular dynamics simulation analysis showed that NAR acts by inhibiting CDK1 by stably occupying its ATP-binding cavity. Considering diet has been listed as a risk factor for stroke, NAR may be explored as a component of functional food for stroke or related neurological disorders.

柚皮苷(NAR)是一种黄酮苷,广泛存在于柑橘类水果、蔬菜和酒精饮料中。尽管有证据表明柚皮苷对缺血性中风动物模型具有神经保护作用,但有关柚皮苷抗氧化功效的脑细胞特异性数据以及这种有益作用的可能蛋白靶点却很有限。在这里,我们利用 MTT 和 DCFDA 检测法,在体外氧-葡萄糖剥夺(OGD)脑缺血模型中证明了 NAR(一种美国食品药物管理局(FDA)批准上市的食品添加剂)对脑细胞特异性的预防作用。利用基于贝叶斯定理的预测模型,我们首先从289个NAR与神经元相互作用的蛋白质中筛选出可能在OGD模型中介导其抗氧化作用的前10个蛋白质靶点(ALDH2、ACAT1、CTSB、FASN、LDHA、PTGS1、CTSD、LGALS1、TARDBP和CDK1)。用 NAR 预孵育 2 天后,N2a 和 CTX-TNA2 细胞可承受长达 8 小时的 OGD,而细胞活力不会明显下降。这种脑保护作用部分是通过减少上述两种脑细胞中细胞内 ROS 的产生来实现的。NAR 的抗氧化作用与临床常用的 ROS 清除剂和神经保护剂依达拉奉的等摩尔浓度(50 µM)相当。NAR 与贝叶斯分析法得出的前 10 位蛋白质靶标的分子对接显示,与 CDK1 的结合能最低(- 8.8 kcal/M)。分子动力学模拟分析表明,NAR 通过稳定地占据 CDK1 的 ATP 结合腔来抑制 CDK1。考虑到饮食已被列为中风的危险因素之一,NAR 可作为治疗中风或相关神经系统疾病的功能性食品成分进行研究。
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引用次数: 0
Assessing Stroke Recurrence Risk by Using a Lipoprotein-Associated Phospholipase A2 and Platelet Count-Based Nomogram. 使用基于脂蛋白相关磷脂酶 A2 和血小板计数的提名图评估中风复发风险。
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-08-23 DOI: 10.1007/s12035-024-04439-3
Yanlong Zhou, Yu Feng, Ning Xin, Jun Lu, Xingshun Xu

Stroke recurrence remains a critical challenge in clinical neurology, necessitating the identification of reliable predictive markers for better management and treatment strategies. This study investigates the interaction between lipoprotein-associated phospholipase A2 (Lp-PLA2) and platelets as a potential predictor for stroke recurrence, aiming to refine risk assessment and therapeutic approaches. In a retrospective cohort of 580 ischemic stroke patients, we analyzed clinical data with a focus on Lp-PLA2 and platelet levels. By using multivariable logistic regression, we identified independent predictors of stroke recurrence. These predictors were then used to develop a comprehensive nomogram. The study established diabetes mellitus, hypertension, low-density lipoprotein (LDL), Lp-PLA2 levels, and platelet counts as independent predictors of stroke recurrence. Crucially, the interaction parameter Lp-PLA2 * platelet (multiplication of Lp-PLA2 and platelet count) exhibited superior predictive power over each factor considered separately. Our nomogram incorporated diabetes mellitus, cerebral infarction causes, hypertension, LDL, and the Lp-PLA2 * platelet count interaction and demonstrated enhanced accuracy in predicting stroke recurrence compared to traditional risk models. The interaction between Lp-PLA2 and platelets emerged as a significant predictor for stroke recurrence when integrated with traditional risk factors. The developed nomogram offers a novel and practical tool in molecular neurobiology for assessing individual risks, facilitating personalized treatment strategies. This approach underscores the importance of multifactorial assessment in stroke management and opens avenues for targeted interventions to mitigate recurrence risks.

脑卒中复发仍然是临床神经病学的一项重大挑战,因此有必要确定可靠的预测标志物,以便制定更好的管理和治疗策略。本研究探讨了脂蛋白相关磷脂酶 A2(Lp-PLA2)与血小板之间的相互作用,以此作为中风复发的潜在预测指标,旨在完善风险评估和治疗方法。在 580 例缺血性中风患者的回顾性队列中,我们分析了临床数据,重点是 Lp-PLA2 和血小板水平。通过使用多变量逻辑回归,我们确定了中风复发的独立预测因素。然后利用这些预测因素制定了一个综合提名图。研究确定糖尿病、高血压、低密度脂蛋白 (LDL)、Lp-PLA2 水平和血小板计数是中风复发的独立预测因素。最重要的是,交互参数 Lp-PLA2 * 血小板(Lp-PLA2 与血小板计数的乘积)的预测能力优于单独考虑的每个因素。我们的提名图纳入了糖尿病、脑梗塞原因、高血压、低密度脂蛋白以及 Lp-PLA2 * 血小板计数的交互作用,与传统的风险模型相比,在预测中风复发方面表现出更高的准确性。Lp-PLA2 与血小板之间的相互作用与传统风险因素相结合,成为中风复发的重要预测因素。所开发的提名图为分子神经生物学评估个体风险提供了一种新颖实用的工具,有助于制定个性化治疗策略。这种方法强调了多因素评估在中风治疗中的重要性,并为采取有针对性的干预措施降低复发风险开辟了途径。
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引用次数: 0
Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation. 电针通过Foxp3乙酰化调控促进缺血性脑卒中后肠道Treg细胞的生成
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-09-25 DOI: 10.1007/s12035-024-04500-1
Yonglin Chen, Ling Ouyang, Xinyi Yang, Bufan Wu, Lingling Meng, Jialin Gu, Yaling Wang, Juan Li, Jingjing Zhang, Xinyue Jing, Shengfeng Lu, Lanying Liu, Shuping Fu

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.

电针(EA)已被证明可改善缺血性中风后的脑损伤并保护肠道免受损伤。这些保护作用与增强肠道调节性 T(Treg)细胞的数量和功能、抑制肠道 γδ T 细胞的产生及其向大脑的迁移密切相关。本研究旨在阐明 EA 调节脑卒中后肠道 Treg 细胞分化的潜在机制。研究将 Sprague-Dawley 大鼠分为三组:假组、大脑中动脉闭塞(MCAO)组和 MCAO 加 EA(MEA)组。MCAO 模型通过闭塞大脑中动脉产生。每天一次在百会穴(GV20)上注射 EA。再灌注3天后收集样本。结果表明,EA能减轻缺血性中风后大脑和肠道的炎症反应。EA治疗增加了大鼠小肠中Treg细胞的比例。EA 增加了 SCFAs 的水平,同时还抑制了组蛋白去乙酰化酶(HDAC)的活性。此外,EA 处理后小肠中乙酰化的 Foxp3 蛋白增加。这些结果表明,GV20 的 EA 可减轻中风大鼠的脑和肠道炎症损伤,这可能是通过增强 Treg 细胞中 SCFA 介导的 Foxp3 乙酰化作用实现的。
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引用次数: 0
Gut Microbiota Mediates Neuroinflammation in Alzheimer's Disease: Unraveling Key Factors and Mechanistic Insights. 肠道微生物群介导阿尔茨海默病的神经炎症:揭示关键因素和机理。
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-09-25 DOI: 10.1007/s12035-024-04513-w
Liang Junyi, Wang Yueyang, Liu Bin, Dong Xiaohong, Cai Wenhui, Zhang Ning, Zhang Hong

The gut microbiota, the complex community of microorganisms that inhabit the gastrointestinal tract, has emerged as a key player in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by progressive cognitive decline and neuronal loss, associated with the accumulation of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation in the brain. Increasing evidence suggests that alterations in the composition and function of the gut microbiota, known as dysbiosis, may contribute to the development and progression of AD by modulating neuroinflammation, a chronic and maladaptive immune response in the central nervous system. This review aims to comprehensively analyze the current role of the gut microbiota in regulating neuroinflammation and glial cell function in AD. Its objective is to deepen our understanding of the pathogenesis of AD and to discuss the potential advantages and challenges of using gut microbiota modulation as a novel approach for the diagnosis, treatment, and prevention of AD.

肠道微生物群是栖息在胃肠道中的复杂微生物群落,已成为包括阿尔茨海默病(AD)在内的神经退行性疾病发病机制的关键因素。阿尔茨海默病的特征是认知能力逐渐下降和神经元丧失,与大脑中淀粉样β斑块、神经纤维缠结和神经炎症的积累有关。越来越多的证据表明,肠道微生物群组成和功能的改变,即所谓的菌群失调,可能会通过调节神经炎症(中枢神经系统的一种慢性和适应不良的免疫反应)而导致 AD 的发生和发展。本综述旨在全面分析目前肠道微生物群在调节 AD 中神经炎症和神经胶质细胞功能中的作用。其目的是加深我们对 AD 发病机制的理解,并讨论将肠道微生物群调节作为诊断、治疗和预防 AD 的一种新方法的潜在优势和挑战。
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引用次数: 0
Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization. 通过线粒体相关全基因组孟德尔随机化鉴定神经退行性疾病的潜在致病基因。
IF 4.6 2区 医学 Q1 NEUROSCIENCES Pub Date : 2025-03-01 Epub Date: 2024-09-30 DOI: 10.1007/s12035-024-04528-3
Kang-Fu Yin, Ting Chen, Xiao-Jing Gu, Zheng Jiang, Wei-Ming Su, Qing-Qing Duan, Xiang-Jin Wen, Bei Cao, Ju-Rong Li, Li-Yi Chi, Yong-Ping Chen

Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.

目前的研究缺乏对线粒体相关基因与神经退行性疾病(NDDs)风险之间潜在因果关系的全面调查。我们的目的是通过研究线粒体相关基因的表达水平,找出五种 NDD 的潜在致病基因。通过整合来自表达定量性状位点(eQTL)数据集(人类血液和脑组织)、线粒体 DNA 拷贝数(mtDNA-CN)和欧洲血统的五种 NDDs 的全基因组关联研究(GWAS)数据集的汇总统计、我们进行了孟德尔随机化(MR)分析,以探讨线粒体相关基因与阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS)、额颞叶痴呆症(FTD)和路易体痴呆症(LBD)之间的潜在因果关系。我们采用了敏感性分析和贝叶斯共定位来验证这种因果关系。通过磁共振分析,我们确定了人体血液或脑组织中 12 个线粒体相关基因与 AD、PD、ALS 和与运动神经元疾病(FTD_MND)重叠的 FTD 之间的潜在因果关系。贝叶斯共定位分析进一步证实了 9 个因果基因,其中 NDUFS2、EARS2 和 MRPL41 与 AD 有关;NDUFAF2、MALSU1 和 METTL8 与 PD 有关;MYO19 和 MRM1 与 ALS 有关;FASTKD1 与 FTD_MND 有关。重要的是,在人类血液和脑组织中,NDUFS2 对注意力缺失症有显著的致病作用,而 NDUFAF2 则对注意力缺失症有强大的保护作用。此外,mtDNA-CN 在 LBD 中也起着保护作用(OR = 0.62,p = 0.031)。本研究提供了线粒体功能障碍与 NDD 之间因果关系的证据。此外,已确定的候选基因可作为药物开发的潜在靶点,以预防 NDDs。
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引用次数: 0
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Molecular Neurobiology
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