Journal of Molecular Neuroscience最新文献

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Transcriptomic Analysis of Lipid Metabolism Genes in Alzheimer’s Disease: Highlighting Pathological Outcomes and Compartmentalized Immune Status 阿尔茨海默病脂质代谢基因转录组分析:突显病理结果和分区免疫状态。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-05-22 DOI: 10.1007/s12031-024-02225-3
Yue Sun, Mengni Jiang, Xiang Long, Yongzhen Miao, Huanhuan Du, Ting Zhang, Xuejun Ma, Yue Zhang, Hongrui Meng
{"title":"Transcriptomic Analysis of Lipid Metabolism Genes in Alzheimer’s Disease: Highlighting Pathological Outcomes and Compartmentalized Immune Status","authors":"Yue Sun,&nbsp;Mengni Jiang,&nbsp;Xiang Long,&nbsp;Yongzhen Miao,&nbsp;Huanhuan Du,&nbsp;Ting Zhang,&nbsp;Xuejun Ma,&nbsp;Yue Zhang,&nbsp;Hongrui Meng","doi":"10.1007/s12031-024-02225-3","DOIUrl":"10.1007/s12031-024-02225-3","url":null,"abstract":"<div><p>The dysregulation of lipid metabolism has been strongly associated with Alzheimer’s disease (AD) and has intricate connections with various aspects of disease progression, such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Here, a comprehensive bioinformatic assessment was conducted on lipid metabolism genes in the brains and peripheral blood of AD-derived transcriptome datasets, characterizing the correlation between differentially expressed genes (DEGs) of lipid metabolism and disease pathologies, as well as immune cell preferences. Through the application of weighted gene co-expression network analysis (WGCNA), modules eigengenes related to lipid metabolism were pinpointed, and the examination of their molecular functions within biological processes, molecular pathways, and their associations with pathological phenotypes and molecular networks has been characterized. Analysis of biological networks indicates notable discrepancies in the expression patterns of the DEGs between neuronal and immune cells, as well as variations in cell type enrichments within both brain tissue and peripheral blood. Additionally, drugs targeting the DEGs from central and peripheral and a diagnostic model for hub genes from the blood were retrieved and assessed, some of which were shown to be useful for therapeutic and diagnostic. These results revealed the distinctive pattern of transcriptionally abnormal lipid metabolism in central, peripheral, and immune cell activation, providing valuable insight into lipid metabolism for diagnosing and guiding more effective treatment for AD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Biological Overlapping Between Brain Calcifications and Tumorgenesis 探索脑钙化与肿瘤发生之间的生物学重叠。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-05-17 DOI: 10.1007/s12031-024-02230-6
Enrico Souza de Godoy, João Ricardo Mendes de Oliveira
{"title":"Exploring the Biological Overlapping Between Brain Calcifications and Tumorgenesis","authors":"Enrico Souza de Godoy,&nbsp;João Ricardo Mendes de Oliveira","doi":"10.1007/s12031-024-02230-6","DOIUrl":"10.1007/s12031-024-02230-6","url":null,"abstract":"<div><p>This article discusses a rare case of coexistent meningiomas and Primary familial brain calcification (PFBC). PFBC is a neurodegenerative disease characterized by brain calcifications and a variety of neuropsychiatric symptoms and signs, with pathogenic variants in specific genes. The study explores the potential link between PFBC and meningiomas, highlighting shared features like intralesional calcifications and common genes such as MEA6. The article also revisits PFBC patients developing other brain tumors, particularly gliomas, emphasizing the intersection of oncogenes like PDGFB and PDGFRB in both calcifications and tumor progression. In recent investigations, attention has extended beyond brain tumors to breast cancer metastasis, unveiling a noteworthy connection. These findings suggest a broader connection between brain calcifications and tumors, encouraging a reevaluation of therapeutic approaches for PFBC.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reversibility of Endoplasmic Reticulum Stress Markers During Long-Term Glucose Starvation in Astrocytes 星形胶质细胞在长期葡萄糖饥饿过程中内质网应激标记物的可逆性
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-05-16 DOI: 10.1007/s12031-024-02223-5
Clara Voelz, Lena E. M. Schaack, Vanessa Kogel, Cordian Beyer, Jochen Seitz, Stefanie Trinh
{"title":"Reversibility of Endoplasmic Reticulum Stress Markers During Long-Term Glucose Starvation in Astrocytes","authors":"Clara Voelz,&nbsp;Lena E. M. Schaack,&nbsp;Vanessa Kogel,&nbsp;Cordian Beyer,&nbsp;Jochen Seitz,&nbsp;Stefanie Trinh","doi":"10.1007/s12031-024-02223-5","DOIUrl":"10.1007/s12031-024-02223-5","url":null,"abstract":"<div><p>Previous studies have demonstrated a brain volume decrease linked to long-term starvation in patients with anorexia nervosa (AN). Food intake is critically diminished in this disorder, leading to one of the highest mortality rates within the psychiatric disease spectrum. As reported in animal models, astrocytes seem to be the most affected cell type in AN. In a recently established primary cell culture model, an elevated unfolded protein response (UPR) was observed in long-term glucose semi-starved astrocytes. A well-functioning protein machinery is essential for every cell, and prolonged UPR will lead to cell death. As a nucleic acid stress-sensing pathway with the activator located in the endoplasmic reticulum, the regulation of the cGAS-STING pathway (cyclic GMP-AMP synthase/stimulator of interferon genes) was additionally investigated in the starvation context. In the current study, a glucose semi-starvation protocol of 15 days, during which cells were supplied with 2 mM glucose in the medium, was prolonged with an additional 6-day long recovery period. Our findings showed that increased UPR mRNA expression was reversible after re-establishing the standard glucose concentration of 25 mM. Furthermore, we were able to verify the presence of cGAS and STING in astrocytes with a characteristic presence of cGAS in the astrocyte nucleus during starvation. A correlation between STING and the glial fibrillary acidic protein (GFAP) could be established, hinting at a conditional presence of STING with a specific astrocyte phenotype.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glutamine Metabolism Heterogeneity in Glioblastoma Unveils an Innovative Combination Therapy Strategy 胶质母细胞瘤中的谷氨酰胺代谢异质性揭示了一种创新的联合疗法策略。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-05-10 DOI: 10.1007/s12031-024-02201-x
Huangde Fu, Shengtian Wu, Hechun Shen, Kai Luo, Zhongxiang Huang, Nankun Lu, Yaolin Li, Qian Lan, Yishun Xian
{"title":"Glutamine Metabolism Heterogeneity in Glioblastoma Unveils an Innovative Combination Therapy Strategy","authors":"Huangde Fu,&nbsp;Shengtian Wu,&nbsp;Hechun Shen,&nbsp;Kai Luo,&nbsp;Zhongxiang Huang,&nbsp;Nankun Lu,&nbsp;Yaolin Li,&nbsp;Qian Lan,&nbsp;Yishun Xian","doi":"10.1007/s12031-024-02201-x","DOIUrl":"10.1007/s12031-024-02201-x","url":null,"abstract":"<div><p>Treatment of glioblastoma multiforme (GBM) remains challenging. Unraveling the orchestration of glutamine metabolism may provide a novel viewpoint on GBM therapy. The study presented a full and comprehensive comprehending of the glutamine metabolism atlas and heterogeneity in GBM for facilitating the development of a more effective therapeutic choice. Transcriptome data from large GBM cohorts were integrated in this study. A glutamine metabolism-based classification was established through consensus clustering approach, and a classifier by LASSO analysis was defined for differentiating the classification. Prognosis, signaling pathway activity, tumor microenvironment, and responses to immune checkpoint blockade (ICB) and small molecular drugs were characterized in each cluster. A combinational therapy of glutaminase inhibitor CB839 with dihydroartemisinin (DHA) was proposed, and the influence on glutamine metabolism, apoptosis, reactive oxygen species (ROS), and migration was measured in U251 and U373 cells. We discovered that GBM presented heterogeneous glutamine metabolism–based clusters, with unique survival outcomes, activity of signaling pathways, tumor microenvironment, and responses to ICB and small molecular compounds. In addition, the classifier could accurately differentiate the two clusters. Strikingly, the combinational therapy of CB839 with DHA synergistically attenuated glutamine metabolism, triggered apoptosis and ROS accumulation, and impaired migrative capacity in GBM cells, demonstrating the excellent preclinical efficacy. Altogether, our findings unveil the glutamine metabolism heterogeneity in GBM and propose an innovative combination therapy of CB839 with DHA for this malignant disease.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomarkers of Alzheimer’s Disease Associated with Programmed Cell Death Reveal Four Repurposed Drugs 与程序性细胞死亡相关的阿尔茨海默氏症生物标志物揭示了四种再利用药物。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-05-03 DOI: 10.1007/s12031-024-02228-0
Elif Kubat Oktem
{"title":"Biomarkers of Alzheimer’s Disease Associated with Programmed Cell Death Reveal Four Repurposed Drugs","authors":"Elif Kubat Oktem","doi":"10.1007/s12031-024-02228-0","DOIUrl":"10.1007/s12031-024-02228-0","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia. Programmed cell death (PCD) is mainly characterized by unique morphological features and energy-dependent biochemical processes. The predominant pathway leading to cell death in AD has not been thoroughly analyzed, although there is evidence of neuron loss in AD and numerous pathways of PCD have been associated with this process. A better understanding of the systems biology underlying the relationship between AD and PCD could lead to the development of new therapeutic approaches. To this end, publicly available transcriptome data were examined using bioinformatic methods such as differential gene expression and weighted gene coexpression network analysis (WGCNA) to find PCD-related AD biomarkers. The diagnostic significance of these biomarkers was evaluated using a logistic regression-based predictive model. Using these biomarkers, a multifactorial regulatory network was developed. Last, a drug repositioning study was conducted to propose new drugs for the treatment of AD targeting PCD. The development of 3PM (predictive, preventive, and personalized) drugs for the treatment of AD would be enabled by additional research on the effects of these drugs on this disease.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aneuploidy is Linked to Neurological Phenotypes Through Oxidative Stress 非整倍体通过氧化应激与神经系统表型有关
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-05-02 DOI: 10.1007/s12031-024-02227-1
Anowarul Islam, Zeeshan Shaukat, Rashid Hussain, Michael G. Ricos, Leanne M. Dibbens, Stephen L. Gregory
{"title":"Aneuploidy is Linked to Neurological Phenotypes Through Oxidative Stress","authors":"Anowarul Islam,&nbsp;Zeeshan Shaukat,&nbsp;Rashid Hussain,&nbsp;Michael G. Ricos,&nbsp;Leanne M. Dibbens,&nbsp;Stephen L. Gregory","doi":"10.1007/s12031-024-02227-1","DOIUrl":"10.1007/s12031-024-02227-1","url":null,"abstract":"<div><p>Aneuploidy, having an aberrant genome, is gaining increasing attention in neurodegenerative diseases. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. A growing body of research from numerous laboratories suggests that many neurodegenerative disorders, especially Alzheimer’s disease and frontotemporal dementia, are characterised by neuronal aneuploidy and the ensuing apoptosis, which may contribute to neuronal loss. Using <i>Drosophila</i> as a model, we investigated the effect of induced aneuploidy in GABAergic neurons. We found an increased proportion of aneuploidy due to <i>Mad2</i> depletion in the third-instar larval brain and increased cell death. Depletion of <i>Mad2</i> in GABAergic neurons also gave a defective climbing and seizure phenotype. Feeding animals an antioxidant rescued the climbing and seizure phenotype. These findings suggest that increased aneuploidy leads to higher oxidative stress in GABAergic neurons which causes cell death, climbing defects, and seizure phenotype. Antioxidant feeding represents a potential therapy to reduce the aneuploidy-driven neurological phenotype.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02227-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Behavioral and Metabolic Effects of ABCG4 KO in the APPswe,Ind (J9) Mouse Model of Alzheimer’s Disease APPswe,Ind (J9) 阿尔茨海默病小鼠模型中 ABCG4 KO 对行为和代谢的影响。
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-04-26 DOI: 10.1007/s12031-024-02214-6
Vincent Fong, Babunageswararao Kanuri, Owen Traubert, Min Lui, Shailendra B. Patel
{"title":"Behavioral and Metabolic Effects of ABCG4 KO in the APPswe,Ind (J9) Mouse Model of Alzheimer’s Disease","authors":"Vincent Fong,&nbsp;Babunageswararao Kanuri,&nbsp;Owen Traubert,&nbsp;Min Lui,&nbsp;Shailendra B. Patel","doi":"10.1007/s12031-024-02214-6","DOIUrl":"10.1007/s12031-024-02214-6","url":null,"abstract":"<div><p>The pathogenesis of Alzheimer’s disease (AD) is complex and involves an imbalance between production and clearance of amyloid-ß peptides (Aß), resulting in accumulation of Aß in senile plaques. Hypercholesterolemia is a major risk factor for developing AD, with cholesterol shown to accumulate in senile plaques and increase production of Aß. ABCG4 is a member of the ATP-binding cassette transporters predominantly expressed in the CNS and has been suggested to play a role in cholesterol and Aß efflux from the brain. In this study, we bred <i>Abcg4</i> knockout (KO) with the APP<sup>Swe,Ind</sup> (J9) mouse model of AD to test the hypothesis that loss of <i>Abcg4</i> would exacerbate the AD phenotype. Unexpectedly, no differences were observed in novel object recognition (NOR) and novel object placement (NOP) behavioral tests, or on histologic examinations of brain tissues for senile plaque numbers. Furthermore, clearance of radiolabeled Aß from the brains did not differ between <i>Abcg4</i> KO and control mice. Metabolic testing by indirect calorimetry, glucose tolerance test (GTT), and insulin tolerance test (ITT) were also mostly similar between groups with only a few mild metabolic differences noted. Overall, these data suggest that the loss of ABCG4 did not exacerbate the AD phenotype.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02214-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Prognostic Methylation-Driven Two-Gene Signature in Medulloblastoma 髓母细胞瘤的预后甲基化双基因特征
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-04-25 DOI: 10.1007/s12031-024-02203-9
Gustavo Lovatto Michaelsen, Lívia dos Reis Edinger da Silva, Douglas Silva de Lima, Mariane da Cunha Jaeger, André Tesainer Brunetto, Rodrigo Juliani Siqueira Dalmolin, Marialva Sinigaglia
{"title":"A Prognostic Methylation-Driven Two-Gene Signature in Medulloblastoma","authors":"Gustavo Lovatto Michaelsen,&nbsp;Lívia dos Reis Edinger da Silva,&nbsp;Douglas Silva de Lima,&nbsp;Mariane da Cunha Jaeger,&nbsp;André Tesainer Brunetto,&nbsp;Rodrigo Juliani Siqueira Dalmolin,&nbsp;Marialva Sinigaglia","doi":"10.1007/s12031-024-02203-9","DOIUrl":"10.1007/s12031-024-02203-9","url":null,"abstract":"<div><p>Medulloblastoma (MB) is one of the most common pediatric brain tumors and it is estimated that one-third of patients will not achieve long-term survival. Conventional prognostic parameters have limited and unreliable correlations with MB outcome, presenting a major challenge for patients’ clinical improvement. Acknowledging this issue, our aim was to build a gene signature and evaluate its potential as a new prognostic model for patients with the disease. In this study, we used six datasets totaling 1679 samples including RNA gene expression and DNA methylation data from primary MB as well as control samples from healthy cerebellum. We identified methylation-driven genes (MDGs) in MB, genes whose expression is correlated with their methylation. We employed LASSO regression, incorporating the MDGs as a parameter to develop the prognostic model. Through this approach, we derived a two-gene signature (GS-2) of candidate prognostic biomarkers for MB (<i>CEMIP</i> and <i>NCBP3</i>). Using a risk score model, we confirmed the GS-2 impact on overall survival (OS) with Kaplan-Meier analysis. We evaluated its robustness and accuracy with receiver operating characteristic curves predicting OS at 1, 3, and 5 years in multiple independent datasets. The GS-2 showed highly significant results as an independent prognostic biomarker compared to traditional MB markers. The methylation-regulated GS-2 risk score model can effectively classify patients with MB into high and low-risk, reinforcing the importance of this epigenetic modification in the disease. Such genes stand out as promising prognostic biomarkers with potential application for MB treatment.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms 识别胶质母细胞瘤患者长期存活者的预测模型:整合机器学习算法的队列研究
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-04-25 DOI: 10.1007/s12031-024-02218-2
Xi-Lin Yang, Zheng Zeng, Chen Wang, Yun-Long Sheng, Guang-Yu Wang, Fu-Quan Zhang, Xin Lian
{"title":"Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms","authors":"Xi-Lin Yang,&nbsp;Zheng Zeng,&nbsp;Chen Wang,&nbsp;Yun-Long Sheng,&nbsp;Guang-Yu Wang,&nbsp;Fu-Quan Zhang,&nbsp;Xin Lian","doi":"10.1007/s12031-024-02218-2","DOIUrl":"10.1007/s12031-024-02218-2","url":null,"abstract":"<div><p>We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS&lt;1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (<i>P</i>&lt;0.05) and greater infiltration of immune suppression cells compared to LTS (<i>P</i>&lt;0.05). Four genes, namely, <i>OSMR</i>, <i>FMOD</i>, <i>CXCL14</i>, and <i>TIMP1</i>, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (<i>C</i>-index, 0.791; 0.772–0.817) and validation cohort (<i>C</i>-index, 0.770; 0.751–0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expression Patterns of miRNAs in Egyptian Children with ADHD: Clinical Study with Correlation Analysis 埃及多动症儿童体内 miRNAs 的表达模式:临床研究与相关性分析
IF 2.8 4区 医学
Journal of Molecular Neuroscience Pub Date : 2024-04-23 DOI: 10.1007/s12031-024-02220-8
Hala M. Zeidan, Neveen Hassan Nashaat, Maha Hemimi, Adel F. Hashish, Amal Elsaeid, Nagwa Abd EL-Ghaffar, Suzette I. Helal, Nagwa A. Meguid
{"title":"Expression Patterns of miRNAs in Egyptian Children with ADHD: Clinical Study with Correlation Analysis","authors":"Hala M. Zeidan,&nbsp;Neveen Hassan Nashaat,&nbsp;Maha Hemimi,&nbsp;Adel F. Hashish,&nbsp;Amal Elsaeid,&nbsp;Nagwa Abd EL-Ghaffar,&nbsp;Suzette I. Helal,&nbsp;Nagwa A. Meguid","doi":"10.1007/s12031-024-02220-8","DOIUrl":"10.1007/s12031-024-02220-8","url":null,"abstract":"<div><p>ADHD has huge knowledge gaps concerning its etiology. MicroRNAs (miRNAs) provide promising diagnostic biomarkers of human pathophysiology and may be a novel therapeutic option. The aim was to investigate the levels of miR-34c-3p, miR-155, miR-138-1, miR-296-5p, and plasma brain-derived neurotrophic factor (BDNF) in a group of children with ADHD compared to neurotypicals and to explore correlations between these measures and some clinical data. The participants were children with ADHD in Group I (<i>N</i> = 41; age: 8.2 ± 2) and neurotypical ones in Group II (<i>N</i> = 40; age: 8.6 ± 2.5). Group I was subjected to clinical examination, the Stanford Binet intelligence scale-5, the preschool language scale, and Conner’s parent rating scale-R. Measuring the expression levels of the miRNAs was performed by <i>qRT-PCR</i> for all participants. The BDNF level was measured by ELISA. The lowest scores on the IQ subtest were knowledge and working memory. No discrepancies were noticed between the receptive and expressive language ages. The highest scores on the Conner’s scale were those for cognitive problems. Participants with ADHD exhibited higher plasma BDNF levels compared to controls (<i>p</i> = 0.0003). Expression patterns of only miR-34c-3p and miR-138-1 were downregulated with significant statistical differences (p˂0.01). However, expression levels of miR-296-5p showed negative correlation with the total scores of IQ (<i>p</i> = 0.03). MiR-34c-3p, miR-138-1, while BDNF showed good diagnostic potential. The downregulated levels of miR-34c-3p and miR-138-1, together with high BDNF levels, are suggested to be involved in the etiology of ADHD in Egyptian children. Gender differences influenced the expression patterns of miRNAs only in children with ADHD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02220-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140669019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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