Journal of Molecular Neuroscience最新文献

{"title":"MiR-126 and miR-146a as Melatonin-Responsive Biomarkers for Neonatal Brain Ischemia","authors":"Maria Cristina Albertini,&nbsp;Tania Vanzolini,&nbsp;Serafina Perrone,&nbsp;Michael D. Weiss,&nbsp;Giuseppe Buonocore,&nbsp;Valentina Dell’Orto,&nbsp;Walter Balduini,&nbsp;Silvia Carloni","doi":"10.1007/s12031-023-02155-6","DOIUrl":"10.1007/s12031-023-02155-6","url":null,"abstract":"<div><p>Despite advances in obstetric and neonatal care, challenges remain in early identification of neonates with encephalopathy due to hypoxia-ischemia who are undergoing therapeutic hypothermia. Therefore, there is a deep search for biomarkers that can identify brain injury. The aims of this study were to investigate the serum and brain expressions of two potential biomarkers, miR-126/miR-146a, in a preclinical model of hypoxia-ischemia (HI)–induced brain injury, and to explore their modulation during melatonin treatment. Seven-day-old rats were subjected to permanent ligation of the right carotid artery followed by 2.5 h hypoxia (HI). Melatonin (15 mg/kg) was administered 5 min after HI. Serum and brain samples were collected 1, 6 and 24 h after HI. Results show that HI caused a significant increase in the circulating levels of both miR-126 and miR-146a during the early phase of ischemic brain damage development (i.e. 1 h), with a parallel and opposite pattern in the ischemic cerebral cortex. These effects are not observed 24 h later. Treatment with melatonin restored the HI-induced effects on miR-126/miR-146a expressions, both in the cerebral cortex and in serum. We conclude that miR-126/miR-146a are promising biomarkers of HI injury and demonstrate an associated change in concentration following melatonin treatment.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"763 - 772"},"PeriodicalIF":3.1,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41092105","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}

{"title":"Identification of Novel Circular RNA Targets in Key Penumbra Region of Rats After Cerebral Ischemia-Reperfusion Injury","authors":"Jiabei Ye,&nbsp;Yudong Shan,&nbsp;Xiaohong Zhou,&nbsp;Tian Tian,&nbsp;Weijuan Gao","doi":"10.1007/s12031-023-02153-8","DOIUrl":"10.1007/s12031-023-02153-8","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are abundantly and stably expressed in the brain of mammals and humans. Some circRNAs are implicated in ischemic stroke. Therefore, we aimed to detect how circRNAs change in the key penumbra area during cerebral ischemia-reperfusion (CI/R) injury. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), during which the permanent blocking period was 2 h and reperfusion time was 24 or 72 h. Then modified neurologic severity score (mNSS), triphenyl tetrazolium chloride (TTC) staining and HE staining were used to exhibiting damage between rats in different groups. The penumbra regions of all rats were dissected and total RNA was further processed for high-throughput sequencing. CircRNA expression profiles were screened and bioinformatics analyses were conducted to investigate these differentially expressed circRNAs. Some of them were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the establishment of a circRNA-miRNA-mRNA network and the detection of their downstream molecules. A total of 99 and 98 circRNAs were differentially expressed at CI/R 24 h and CI/R 72 h, respectively. Notably, 21 circRNAs significantly changed at both reperfusion points. Three circRNAs, namely circ.7225, circ.5415, and circ.20623 were found to be associated with CI/R injury and might be preferred targets. Common downstream miR-298-5p and Bcl-3 were found to make up the circRNA-miRNA-mRNA network. Novel circRNA targets came to light in the penumbra of rats during CI/R injury and might establish the circRNA-miRNA-mRNA relationship, thus serving as potential biomarkers for ischemic stroke treatment.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"751 - 762"},"PeriodicalIF":3.1,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188891","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}

{"title":"Evaluating Gene Expression and Methylation Profiles of TCF4, MBP, and EGR1 in Peripheral Blood of Drug-Free Patients with Schizophrenia: Correlations with Psychopathology, Intelligence, and Cognitive Impairment","authors":"Fatemeh Yazarlou,&nbsp;Mobina Tabibian,&nbsp;Asaad Azarnezhad,&nbsp;Habib Sadeghi Rad,&nbsp;Leonard Lipovich,&nbsp;Golshid Sanati,&nbsp;Hamid Mostafavi Abdolmaleky,&nbsp;Fatemeh Alizadeh","doi":"10.1007/s12031-023-02150-x","DOIUrl":"10.1007/s12031-023-02150-x","url":null,"abstract":"<div><p>Discovery and validation of new, reliable diagnostic and predictive biomarkers for schizophrenia (SCZ) are an ongoing effort. Here, we assessed the mRNA expression and DNA methylation of the TCF4, MBP, and EGR1 genes in the blood of patients with SCZ and evaluated their relationships to psychopathology and cognitive impairments. Quantitative real-time PCR and quantitative methylation-specific PCR methods were used to assess the expression level and promoter DNA methylation status of these genes in 70 drug-free SCZ patients and 72 healthy controls. The correlation of molecular changes with psychopathology and cognitive performance of participants was evaluated. We observed downregulation of TCF4 and upregulation of MBP mRNA levels in SCZ cases, relative to controls in our study. DNA methylation status at the promoter region of TCF4 demonstrated an altered pattern in SCZ as well. Additionally, TCF4 mRNA levels were inversely correlated with PANSS and Stroop total errors and positively correlated with WAIS total score and working memory, consistent with previous studies by our group. In contrast, MBP mRNA level was significantly positively correlated with PANSS and Stroop total errors and inversely correlated with WAIS total score and working memory. These epigenetic and expression signatures can help to assemble a peripheral biomarker-based diagnostic panel for SCZ.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"738 - 750"},"PeriodicalIF":3.1,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527724","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}

{"title":"Early Alterations of PACAP and VIP Expression in the Female Rat Brain Following Spinal Cord Injury","authors":"Sarah Thomas Broome,&nbsp;Mawj Mandwie,&nbsp;Catherine A. Gorrie,&nbsp;Giuseppe Musumeci,&nbsp;Rubina Marzagalli,&nbsp;Alessandro Castorina","doi":"10.1007/s12031-023-02151-w","DOIUrl":"10.1007/s12031-023-02151-w","url":null,"abstract":"<div><p>Previous evidence shows that rapid changes occur in the brain following spinal cord injury (SCI). Here, we interrogated the expression of the neuropeptides pituitary adenylyl cyclase-activating peptide (PACAP), vasoactive intestinal peptides (VIP), and their binding receptors in the rat brain 24 h following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy; half of the rats received a mild contusion injury at the level of the T10 vertebrate (SCI group); the other half underwent sham surgery (sham group). Twenty-four hours post-surgery, the hypothalamus, thalamus, amygdala, hippocampus (dorsal and ventral), prefrontal cortex, and periaqueductal gray were collected. PACAP, VIP, PAC1, VPAC1, and VPAC2 mRNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, PACAP expression was increased in the hypothalamus (104–141% vs sham) and amygdala (138–350%), but downregulated in the thalamus (35–95%) and periaqueductal gray (58–68%). VIP expression was increased only in the thalamus (175–385%), with a reduction in the amygdala (51–68%), hippocampus (40–75%), and periaqueductal gray (74–76%). The expression of the PAC1 receptor was the least disturbed by SCI, with decrease expression in the ventral hippocampus (63–68%) only. The expression levels of VPAC1 and VPAC2 receptors were globally reduced, with more prominent reductions of VPAC1 vs VPAC2 in the amygdala (21–70%) and ventral hippocampus (72–75%). In addition, VPAC1 downregulation also extended to the dorsal hippocampus (69–70%). These findings demonstrate that as early as 24 h post-SCI, there are region-specific disruptions of PACAP, VIP, and related receptor transcript and protein levels in supraspinal regions controlling higher cognitive functions.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"724 - 737"},"PeriodicalIF":3.1,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10116287","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}

{"title":"BMP4, SGSH, and SLC11A2 are Predicted to Be Biomarkers of Aging Associated with Programmed Cell Death","authors":"Elif Kubat Oktem","doi":"10.1007/s12031-023-02148-5","DOIUrl":"10.1007/s12031-023-02148-5","url":null,"abstract":"<div><p>Most neurodegenerative diseases are exacerbated by aging, with symptoms often worsening over time. Programmed cell death (PCD) is a controlled cell suicide mechanism that is essential for the stability, growth, and homeostasis of organisms. Understanding the effects of aging at the level of systems biology could lead to new therapeutic approaches for a broad spectrum of neurodegenerative diseases. In the absence of comprehensive functional studies on the relationship between PCD and aging of the prefrontal cortex, this study provides prefrontal brain biomarkers of aging associated with PCD that could open the way for improved therapeutic techniques for age-related neurodegenerative diseases. To this end, publicly available transcriptome data were subjected to bioinformatic analyses such as differential gene expression, functional enrichment, and the weighted gene coexpression network analysis (WGCNA). The diagnostic utility of the biomarkers was tested using a logistic regression-based prediction model. Three genes, namely <i>BMP4</i>, <i>SGSH</i>, and <i>SLC11A2</i>, were found to be aging biomarkers associated with PCD. Finally, a multifactorial regulatory network with interacting proteins, transcription factors (TFs), competing endogenous RNAs (ceRNAs), and microRNAs (miRNAs) was constructed around these biomarkers. The elements of this multifactorial regulatory network were mainly enriched in BMP signaling. Further exploration of these three biomarkers and their regulatory elements would enable the development of 3PM (predictive, preventive, and personalized) medicine for the treatment of age-related neurodegenerative diseases.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"713 - 723"},"PeriodicalIF":3.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10131061","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}

{"title":"Spreading of Tau Protein Does Not Depend on Aggregation Propensity","authors":"Sara Rodrigues,&nbsp;Marta Anglada-Huguet,&nbsp;Katja Hochgräfe,&nbsp;Senthilvelrajan Kaniyappan,&nbsp;Susanne Wegmann,&nbsp;Eva-Maria Mandelkow","doi":"10.1007/s12031-023-02143-w","DOIUrl":"10.1007/s12031-023-02143-w","url":null,"abstract":"<div><p>The stereotypical progression of Tau pathology during Alzheimer disease has been attributed to trans-neuronal spreading of misfolded Tau proteins, followed by prion-like templated aggregation of Tau. The nature of Tau and the cellular mechanisms of Tau spreading are still under debate. We hypothesized that Tau’s propensity for aggregation would correlate with its ability to spread across synapses and propagate pathology. To study the progressive propagation of Tau proteins in brain regions relevant for Alzheimer disease, we used mice expressing near-physiological levels of full-length human Tau protein carrying pro-aggregant (TauΔK280, Tau^ΔK) or anti-aggregant (TauΔK280-PP, Tau^ΔK−PP) mutations in the entorhinal cortex (EC). To enhance Tau expression in the EC, we performed EC injections of adeno-associated virus (AAV) particles encoding Tau^ΔK or Tau^ΔK−PP. The brains of injected and non-injected EC/Tau^ΔK and EC/Tau^ΔK−PP mice were studied by immunohistological and biochemical techniques to detect Tau propagation to dentate gyrus (DG) neurons and Tau-induced pathological changes. Pro- and anti-aggregant mice had comparable low transgene expression (~0.2 times endogenous mouse Tau). They accumulated human Tau at similar rates and only in expressing EC neurons, including their axonal projections of the perforant path and presynaptic terminals in the molecular layer of the DG. Pro-aggregant EC/Tau^ΔK mice showed misfolded Tau and synaptic protein alterations in EC neurons, not observed in anti-aggregant EC/Tau^ΔK−PP mice. Additional AAV-mediated expression of Tau^ΔK or Tau^ΔK−PP in EC/Tau^ΔK or EC/Tau^ΔK−PP mice, respectively, increased the human Tau expression to ~0.65 times endogenous mouse Tau, with comparable spreading of Tau^ΔK and Tau^ΔK−PP throughout the EC. There was a low level of transcellular propagation of Tau protein, without pathological phosphorylation or misfolding, as judged by diagnostic antibodies. Additionally, Tau^ΔK but not Tau^ΔK−PP expression induced hippocampal astrogliosis. Low levels of pro- or anti-aggregant full-length Tau show equivalent distributions in EC neurons, independent of their aggregation propensity. Increasing the expression via AAV induce local Tau misfolding in the EC neurons, synaptotoxicity, and astrogliosis and lead to a low level of detectable trans-neuronal spreading of Tau. This depends on its concentration in the EC, but, contrary to expectations, does not depend on Tau’s aggregation propensity/misfolding and does not lead to templated misfolding in recipient neurons.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 9-10","pages":"693 - 712"},"PeriodicalIF":3.1,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10040547","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}

{"title":"Predicting the Cognitive Ability of Young Women Using a New Feature Selection Algorithm","authors":"Afrooz Arzehgar,&nbsp;Fatemeh Davarinia,&nbsp;Gordon A. Ferns,&nbsp;Ali Hakimi,&nbsp;Afsane Bahrami","doi":"10.1007/s12031-023-02145-8","DOIUrl":"10.1007/s12031-023-02145-8","url":null,"abstract":"<div><p>Cognitive abilities are the capabilities to perform mental processes that include executive function, comprehension, decision-making, work performance, and educational attainment. This study aimed to investigate the relationship between several biomarkers and individuals’ cognitive ability using various machine learning methods. A total of 144 young women aged between 18 and 24 years old were recruited into the study. Cognitive performance was assessed using a standard questionnaire. A panel of biochemical, hematological, inflammatory, and oxidative stress biomarkers in serum and urine was measured for all participants. A novel combination of feature selection and feature scoring techniques within a hierarchical ensemble structure has been proposed to identify the most effective features in recognizing the importance of various biomarker signatures in cognitive abilities classification. Multiple feature selection methods were employed in conjunction with different classifiers to construct this model. In this manner, using three filter methods, the scores of each feature were considered. The combination of high-scoring features for each filter method was stored as the primary feature subset. A high-accuracy feature subset was selected by using a wrapper method. The collection of highly scored features from each filter method formed the primary feature subset. A wrapper method was also employed to select a feature subset with high accuracy. To ensure robustness and minimize random variations in the feature subset search process, a repeative tenfold cross-validation was conducted. The most frequently recurring features were determined. This iterative step facilitated the identification of an optimal feature subset, effectively reducing the dimensionality of features while maintaining accuracy. Among the 47 extracted factors, serum level of NOx (nitrite ± nitrate), alkaline phosphatase (ALP), and phosphate as well as blood platelet count (PLT) was entered into the model of cognitive abilities with the highest accuracy of approximately 70.9% using a decision tree classifier. Therefore, the serum levels of NOx, ALP, phosphate, and blood PLT count may be important markers of the cognitive abilities in apparently healthy young women. These factors my provide a simple procedure to identify mental abilities and earlier cognitive decline in healthy adults.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 7-8","pages":"678 - 691"},"PeriodicalIF":3.1,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080124","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}

{"title":"Understanding the Molecular Regulation of Serotonin Receptor 5-HTR1B-β-Arrestin1 Complex in Stress and Anxiety Disorders","authors":"Oindrilla Dutta Gupta,&nbsp;Izhar Karbat,&nbsp;Kuntal Pal","doi":"10.1007/s12031-023-02146-7","DOIUrl":"10.1007/s12031-023-02146-7","url":null,"abstract":"<div><p>The serotonin receptor subtype 5-HTR_1B is widely distributed in the brain with an important role in various behavioral implications including neurological conditions and psychiatric disorders. The neuromodulatory action of 5-HTR_1B largely depends upon its arrestin mediated signaling pathway. In this study, we tried to investigate the role of unusually long intracellular loop 3 (ICL3) region of the serotonin receptor 5-HTR_1B in interaction with β-arrestin1 (Arr2) to compensate for the absence of the long cytoplasmic tail. Molecular modeling and docking tools were employed to obtain a suitable molecular conformation of the ICL3 region in complex with Arr2 which dictates the specific complex formation of 5-HTR_1B with Arr2. This reveals the novel molecular mechanism of phosphorylated ICL3 mediated GPCR-arrestin interaction in the absence of the long cytoplasmic tail. The in-cell disulfide cross-linking experiments and molecular dynamics simulations of the complex further validate the model of 5-HTR_1B-ICL3-Arr2 complex. Two serine residues (Ser281 and Ser295) within the 5-HTR_1B-ICL3 region were found to be occupying the electropositive pocket of Arr2 in our model and might be crucial for phosphorylation and specific Arr2 binding. The alignment studies of these residues showed them to be conserved only across 5-HTR_1B mammalian species. Thus, our studies were able to predict a molecular conformation of 5-HTR_1B-Arr2 and identify the role of long ICL3 in the signaling process which might be crucial in designing targeted drugs (biased agonists) that promote GPCR-Arr2 signaling to deter the effects of stress and anxiety-like disorders.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 7-8","pages":"664 - 677"},"PeriodicalIF":3.1,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-023-02146-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080272","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}

{"title":"Elucidating the Role of Pyroptosis in Lower-Grade Glioma: Development of a Novel Scoring System to Enhance Personalized Therapeutic Approaches","authors":"Xiao Chen,&nbsp;Ying Xu,&nbsp;Maode Wang,&nbsp;Chunying Ren","doi":"10.1007/s12031-023-02147-6","DOIUrl":"10.1007/s12031-023-02147-6","url":null,"abstract":"<div><p>Pyroptosis, an orchestrated cellular death pathway, has gained attention due to its role in the pathophysiology and evolution of numerous malignancies. Despite this, no robust quantitative measure of pyroptosis activity in lower-grade glioma (LGG) exists currently. We scrutinized the transcriptomic data of LGG specimens acquired from TCGA and CGGA repositories, juxtaposed with the expression patterns of healthy brain tissues from the GTEx database. A register of pyroptosis-associated genes was extracted from the GSEA database. Utilizing unsupervised clustering algorithms on the expression patterns of these genes, we stratified LGG samples into unique subgroups. We implemented the Boruta machine learning algorithm to discern representative variables for each pyroptosis subtype and applied principal component analysis (PCA) to condense the dimensionality of the feature gene expression data, which led to the formulation of a pyroptosis scoring system (P score) to estimate pyroptosis activity in LGG. Furthermore, we affirmed the capacity of the P score to discriminate diverse cell subpopulations within a single-cell database and explored the correlations between the P score and clinical attributes, prognostic implications, and the tumor immune microenvironment in LGG. We identified three distinctive pyroptosis patterns with significant correlations to patient survival, clinicopathological properties, and characteristics of the tumor immune microenvironment (TIME). Two gene clusters, associated with unique prognostic and TIME attributes, emerged from differentially expressed genes (DEGs) across the pyroptosis patterns. The P score was formulated and authenticated as an autonomous prognostic determinant for overall survival in the TCGA and CGGA cohorts. Additionally, the P score demonstrated its competency to quantitatively represent pyroptosis activity across different cellular subpopulations in single-cell data. Notably, the P score in LGG was found to be indicative of tumor stemness and could serve as a predictive biomarker for the efficacy of temozolomide treatment and immunotherapy, underscoring its potential clinical utility. Our investigation pioneers a novel pyroptosis-centric scoring system with significant prognostic implications. The P score holds promise as a potential predictive biomarker for the response to chemotherapy and immunotherapy, facilitating the development of personalized therapeutic approaches in LGG patients.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 7-8","pages":"649 - 663"},"PeriodicalIF":3.1,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-023-02147-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080119","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}

{"title":"Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia","authors":"Kun Lian,&nbsp;Zonglin Shen,&nbsp;Runxu Yang,&nbsp;Jing Ye,&nbsp;Binli Shang,&nbsp;Lei Dong,&nbsp;Hongfang Li,&nbsp;Jiabing Wu,&nbsp;Yuqi Cheng,&nbsp;Xiufeng Xu","doi":"10.1007/s12031-023-02138-7","DOIUrl":"10.1007/s12031-023-02138-7","url":null,"abstract":"<div><p>Schizophrenia (SCZ) is a prevalent, severe, and persistent mental disorder with an unknown etiology. Growing evidence indicates that immunological dysfunction is vital in the development of SCZ. Our study aims to uncover potential immune-linked hub genes and immune infiltration characteristics of SCZ, as well as to develop a diagnostic model based on immune-linked central genes. GSE38484 and GSE54913 chip expression data for patients with SCZ and healthy controls were retrieved. Weighted gene co-expression network analysis (WGCNA) was performed to identify major module genes and critical immune-linked genes. Functional enrichment analysis was conducted to elucidate the involvement of key genes in the immunological response to SCZ, along with the examination of their protein interactions. Moreover, 202 peripheral blood samples were examined using the single-sample gene set enrichment analysis (ssGSEA) method to detect distinct immune cell types. Hub immune-linked genes in SCZ were identified using the minimal absolute contraction and selection operator analysis. Receptor profiles of central immune-linked genes were analyzed to distinguish the two groups. Finally, the association between immune-linked hub genes and various types of immune cells was assessed. Our findings revealed ten immune cell types and nine key genes involved in SCZ, including effector memory CD4+ T cells, activated CD8+ T cells, mast cells, naive CD8+ T cells, PBMC, type 17 helper cells (Th17), central memory CD8+ T cells, CD56 bright NK cells, memory B cells, and regulatory T cells. Diagnostic models constructed using LASSO regression exhibited an average area under the curve (AUC) of 0.866. Our results indicate immunological dysfunction as a factor in the development of SCZ. <i>ASGR2</i>, <i>ADRM1</i>, <i>AHANK</i>, <i>S100A8</i>, <i>FUCA1</i>, <i>AKNA</i>, <i>GATA3</i>, <i>AHCYL2</i>, and <i>PTRH2</i> are the key regulatory genes of immune cells, highlighting their potential as novel therapeutic targets for SCZ.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"73 7-8","pages":"635 - 648"},"PeriodicalIF":3.1,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-023-02138-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080029","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}