NeuroMolecular Medicine最新文献_第10页

Prognosis and Immune Landscapes in Glioblastoma Based on Gene-Signature Related to Reactive-Oxygen-Species. 基于与活性氧物种相关的基因特征的胶质母细胞瘤预后和免疫景观

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 Epub Date: 2022-07-02 DOI: 10.1007/s12017-022-08719-w

Prashant Kaushal, Junle Zhu, Zhiping Wan, Huairui Chen, Jingliang Ye, Chun Luo

{"title":"Prognosis and Immune Landscapes in Glioblastoma Based on Gene-Signature Related to Reactive-Oxygen-Species.","authors":"Prashant Kaushal, Junle Zhu, Zhiping Wan, Huairui Chen, Jingliang Ye, Chun Luo","doi":"10.1007/s12017-022-08719-w","DOIUrl":"10.1007/s12017-022-08719-w","url":null,"abstract":"Glioblastoma (GBM) is the most malignant and aggressive primary brain tumor and is highly resistant to current therapeutic strategies. Previous studies have demonstrated that reactive oxygen species (ROS) play an important role in the regulation of signal transduction and immunosuppressive environment in GBM. To further study the role of ROS in prognosis, tumor micro-environment (TME) and immunotherapeutic response in GBM, an ROS-related nine-gene signature was constructed using the Lasso-Cox regression method and validated using three other datasets in our research, based on the hallmark ROS-pathway-related gene sets and the Cancer Genome Atlas GBM dataset. Differences in prognosis, TME scores, immune cell infiltration, immune checkpoint expression levels, and drug sensitivity between high-risk and low-risk subgroups were analyzed using R software. Collectively, our research uncovered a novel ROS-related prognostic model for primary GBM, which could prove to be a potential tool for clinical diagnosis of GBM, and help assess the immune and molecular characteristics of ROS in the tumorigenesis and immunosuppression of GBM. Our research also revealed that the expressions of ROS-related genes-HSPB1, LSP1, and PTX3-were closely related to the cell markers of tumor-associated macrophages (TAMs) and M2 macrophages validated by quantitative RT-PCR, suggesting them could be potential targets of immunotherapy for GBM.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654266","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

Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons. 培养间充质干细胞代谢转换产生超级线粒体在缺血性神经元的修复中的作用。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 DOI: 10.1007/s12017-022-08720-3

Anna Gorsky, Molly Monsour, Hung Nguyen, Vanessa Castelli, Jea-Young Lee, Cesar V Borlongan

{"title":"Metabolic Switching of Cultured Mesenchymal Stem Cells Creates Super Mitochondria in Rescuing Ischemic Neurons.","authors":"Anna Gorsky, Molly Monsour, Hung Nguyen, Vanessa Castelli, Jea-Young Lee, Cesar V Borlongan","doi":"10.1007/s12017-022-08720-3","DOIUrl":"https://doi.org/10.1007/s12017-022-08720-3","url":null,"abstract":"Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs. Compared to nMSCs, sMSCs displayed higher basal energy production, larger spare respiratory capacity, greater ATP production, and decreased proton leak. Co-culture of OGD-exposed neurons with sMSCs conferred greater cell viability, enhanced cell metabolism, reduced mitochondrial reactive oxidative species mRNA, and elevated mitochondria ATP mRNA than those cultured with nMSCs. Metabolic switching produces \"super\" mitochondria that may underlie the therapeutic benefit of using sMSCs to treat ischemic cells.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10025198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338772","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: 5

Tau and GSK-3β are Critical Contributors to α-Synuclein-Mediated Post-Stroke Brain Damage. Tau和GSK-3β是α-突触核蛋白介导的脑卒中后脑损伤的关键因素。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 Epub Date: 2022-11-30 DOI: 10.1007/s12017-022-08731-0

Suresh L Mehta, TaeHee Kim, Bharath Chelluboina, Raghu Vemuganti

{"title":"Tau and GSK-3β are Critical Contributors to α-Synuclein-Mediated Post-Stroke Brain Damage.","authors":"Suresh L Mehta, TaeHee Kim, Bharath Chelluboina, Raghu Vemuganti","doi":"10.1007/s12017-022-08731-0","DOIUrl":"10.1007/s12017-022-08731-0","url":null,"abstract":"Post-stroke secondary brain damage is significantly influenced by the induction and accumulation of α-Synuclein (α-Syn). α-Syn-positive inclusions are often present in tauopathies and elevated tau levels and phosphorylation promotes neurodegeneration. Glycogen synthase kinase 3β (GSK-3β) is a known promoter of tau phosphorylation. We currently evaluated the interaction of α-Syn with GSK-3β and tau in post-ischemic mouse brain. Transient focal ischemia led to increased cerebral protein-protein interaction of α-Syn with both GSK-3β and tau and elevated tau phosphorylation. Treatment with a GSK-3β inhibitor prevented post-ischemic tau phosphorylation. Furthermore, α-Syn interaction was observed to be crucial for post-ischemic GSK-3β-dependent tau hyperphosphorylation as it was not seen in α-Syn knockout mice. Moreover, tau knockout mice show significantly smaller brain damage after transient focal ischemia. Overall, the present study indicates that GSK-3β catalyzes the α-Syn-dependent tau phosphorylation and preventing this interaction is crucial to limit post-ischemic secondary brain damage.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249510/pdf/nihms-1895702.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596632","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

Gastrodin Regulates the Notch-1 Signal Pathway via Renin-Angiotensin System in Activated Microglia. 天麻素通过肾素-血管紧张素系统调控激活小胶质细胞Notch-1信号通路。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 DOI: 10.1007/s12017-022-08714-1

Fang Wu, Han-Jun Zuo, Xue-Qi Ren, Peng-Xiang Wang, Fan Li, Juan-Juan Li

{"title":"Gastrodin Regulates the Notch-1 Signal Pathway via Renin-Angiotensin System in Activated Microglia.","authors":"Fang Wu, Han-Jun Zuo, Xue-Qi Ren, Peng-Xiang Wang, Fan Li, Juan-Juan Li","doi":"10.1007/s12017-022-08714-1","DOIUrl":"https://doi.org/10.1007/s12017-022-08714-1","url":null,"abstract":"Notch-1 and renin angiotensin system (RAS) are involved in microglia activation. It has been reported that gastrodin inhibited inflammatory responses mediated by activated microglia. This study explored the possible interaction between this two pathways, and to determine whether gastrodin would exert its effects on both of them. Expression of RAS, Notch-1 signaling and proinflammatory mediators in lipopolysaccharide (LPS) activated BV-2 microglia subjected to various treatments was determined by Western blot and immunofluorescence. The protein expression of RAS, Notch-1 pathway and TNF-α and IL-1β was significantly increased in activated microglia. Exogenous Ang II markedly enhanced the expression of these biomarkers. Meanwhile, Azilsartan [a specific inhibitor of AT1 (AT1I)] inhibited the expression of Notch-1 pathway and proinflammatory cytokines. When Notch-1 signaling was inhibited with DAPT, ACE and AT1 expression remained unaffected, indicating that RAS can regulate the Notch-1 pathway in activated microglia but not reciprocally. Additionally, we showed here that gastrodin inhibited the RAS, Notch-1 pathway and inflammatory response. Remarkably, gastrodin did not exert any effect on expression of Notch-1 signaling when RAS was blocked by AT1I, suggesting that gastrodin acts on the RAS directly, not through the Notch-1 pathway. Furthermore, TNF-α and IL-1β expression was significantly increased in activated microglia treated with exogenous Ang II; the expression, however, was suppressed by gastrodin. Of note, expression of proinflammatory cytokines was further decreased in gastrodin and AT1I combination treatment. The results suggest that gastrodin acts via the RAS which regulates the Notch-1 signaling and inflammation in LPS-induced microglia.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9285628","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: 5

The Mood Stabilizer Lithium Slows Down Synaptic Vesicle Cycling at Glutamatergic Synapses. 心境稳定剂锂减缓谷氨酸突触的突触囊泡循环。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 DOI: 10.1007/s12017-022-08729-8

Willcyn Tang, Bradley Cory, Kah-Leong Lim, Marc Fivaz

{"title":"The Mood Stabilizer Lithium Slows Down Synaptic Vesicle Cycling at Glutamatergic Synapses.","authors":"Willcyn Tang, Bradley Cory, Kah-Leong Lim, Marc Fivaz","doi":"10.1007/s12017-022-08729-8","DOIUrl":"https://doi.org/10.1007/s12017-022-08729-8","url":null,"abstract":"Lithium is a mood stabilizer broadly used to prevent and treat symptoms of mania and depression in people with bipolar disorder (BD). Little is known, however, about its mode of action. Here, we analyzed the impact of lithium on synaptic vesicle (SV) cycling at presynaptic terminals releasing glutamate, a neurotransmitter previously implicated in BD and other neuropsychiatric conditions. We used the pHluorin-based synaptic tracer vGpH and a fully automated image processing pipeline to quantify the effect of lithium on both SV exocytosis and endocytosis in hippocampal neurons. We found that lithium selectively reduces SV exocytic rates during electrical stimulation, and markedly slows down SV recycling post-stimulation. Analysis of single-bouton responses revealed the existence of functionally distinct excitatory synapses with varying sensitivity to lithium-some terminals show responses similar to untreated cells, while others are markedly impaired in their ability to recycle SVs. While the cause of this heterogeneity is unclear, these data indicate that lithium interacts with the SV machinery and influences glutamate release in a large fraction of excitatory synapses. Together, our findings show that lithium down modulates SV cycling, an effect consistent with clinical reports indicating hyperactivation of glutamate neurotransmission in BD.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9287185","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: 2

Implication of Paraprobiotics in Age-Associated Gut Dysbiosis and Neurodegenerative Diseases. 副益生菌在年龄相关肠道生态失调和神经退行性疾病中的意义。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 DOI: 10.1007/s12017-022-08722-1

Ziaur Rahman, Manoj P Dandekar

引用次数: 7

What Do Randomized Controlled Trials Inform Us About Potential Disease-Modifying Strategies for Parkinson's Disease? 关于帕金森病的潜在疾病改善策略，随机对照试验告诉了我们什么?

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 DOI: 10.1007/s12017-022-08718-x

Wei-Yi Ong, Damien Meng-Kiat Leow, Deron R Herr, Crystal Jing-Jing Yeo

{"title":"What Do Randomized Controlled Trials Inform Us About Potential Disease-Modifying Strategies for Parkinson's Disease?","authors":"Wei-Yi Ong, Damien Meng-Kiat Leow, Deron R Herr, Crystal Jing-Jing Yeo","doi":"10.1007/s12017-022-08718-x","DOIUrl":"https://doi.org/10.1007/s12017-022-08718-x","url":null,"abstract":"Research advances have shed new insight into cellular pathways contributing to PD pathogenesis and offer increasingly compelling therapeutic targets. In this review, we made a broad survey of the published literature that report possible disease-modifying effects on PD. While there are many studies that demonstrate benefits for various therapies for PD in animal and human studies, we confined our search to human \"randomised controlled trials\" and with the key words \"neuroprotection\" or \"disease-modifying\". It is hoped that through studying the results of these trials, we might clarify possible mechanisms that underlie idiopathic PD. This contrasts with studying the effect of pathophysiology of familial PD, which could be carried out by gene knockouts and animal models. Randomised controlled trials indicate promising effects of MAO-B inhibitors, dopamine agonists, NMDA receptor antagonists, metabotropic glutamate receptor antagonists, therapies related to improving glucose utilization and energy production, therapies related to reduction of excitotoxicity and oxidative stress, statin use, therapies related to iron chelation, therapies related to the use of phytochemicals, and therapies related to physical exercise and brain reward pathway on slowing PD progression. Cumulatively, these approaches fall into two categories: direct enhancement of dopaminergic signalling, and reduction of neurodegeneration. Overlaps between the two categories result in challenges in distinguishing between symptomatic versus disease-modifying effects with current clinical trial designs. Nevertheless, a broad-based approach allows us to consider all possible therapeutic avenues which may be neuroprotective. While the traditional standard of care focuses on symptomatic management with dopaminergic drugs, more recent approaches suggest ways to preserve dopaminergic neurons by attenuating excitotoxicity and oxidative stress.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9284974","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: 2

ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma. ZEB1是髓母细胞瘤预后的亚群特异性标志物和潜在的药物靶点。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2023-03-01 DOI: 10.1007/s12017-022-08716-z

Livia Fratini, Matheus Gibeke Siqueira Dalmolin, Marialva Sinigaglia, Alexandre da Silveira Perla, Caroline Brunetto de Farias, Algemir L Brunetto, André T Brunetto, Mariane da Cunha Jaeger, Rafael Roesler

{"title":"ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma.","authors":"Livia Fratini, Matheus Gibeke Siqueira Dalmolin, Marialva Sinigaglia, Alexandre da Silveira Perla, Caroline Brunetto de Farias, Algemir L Brunetto, André T Brunetto, Mariane da Cunha Jaeger, Rafael Roesler","doi":"10.1007/s12017-022-08716-z","DOIUrl":"https://doi.org/10.1007/s12017-022-08716-z","url":null,"abstract":"Medulloblastoma (MB) is a malignant brain tumor that afflicts mostly children and adolescents and presents four distinct molecular subgroups, known as WNT, SHH, Group 3, and Group 4. ZEB1 is a transcription factor that promotes the expression of mesenchymal markers while restraining expression of epithelial and polarity genes. Because of ZEB1 involvement in cerebellum development, here we investigated the role of ZEB1 in MB. We found increased expression of ZEB1 in MB tumor samples compared to normal cerebellar tissue. Expression was higher in the SHH subgroup when compared to all other MB molecular subgroups. High ZEB1 expression was associated with poor prognosis in Group 3 and Group 4, whereas in patients with WNT tumors poorer prognosis were related to lower ZEB1 expression. There was a moderate correlation between ZEB1 and MYC expression in Group 3 and Group 4 MB. Treatment with the immunomodulator and histone deacetylase (HDAC) inhibitor fingolimod (FTY720) reduced ZEB1 expression specifically in D283 cells, which are representative of Group 3 and Group 4 MB. These findings reveal novel subgroup-specific associations of ZEB1 expression with survival in patients with MB and suggest that ZEB1 expression can be reduced by pharmacological agents that target HDAC activity.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9285733","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: 1

Bim Deletion Reduces Functional Deficits Following Ischemic Stroke in Association with Modulation of Apoptosis and Inflammation. Bim缺失减少缺血性脑卒中后功能缺陷与细胞凋亡和炎症调节的关系

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2022-12-01 Epub Date: 2022-02-11 DOI: 10.1007/s12017-022-08703-4

Jason A Glab, Hamsa Puthalakath, Shenpeng R Zhang, Antony Vinh, Grant R Drummond, Christopher G Sobey, T Michael De Silva, Hyun Ah Kim

{"title":"Bim Deletion Reduces Functional Deficits Following Ischemic Stroke in Association with Modulation of Apoptosis and Inflammation.","authors":"Jason A Glab, Hamsa Puthalakath, Shenpeng R Zhang, Antony Vinh, Grant R Drummond, Christopher G Sobey, T Michael De Silva, Hyun Ah Kim","doi":"10.1007/s12017-022-08703-4","DOIUrl":"https://doi.org/10.1007/s12017-022-08703-4","url":null,"abstract":"Cellular apoptosis is a key pathological mechanism contributing to neuronal death following ischemic stroke. The pro-apoptotic Bcl-2 family protein, Bim, is an important regulator of apoptosis. In this study we investigated the effect of Bim expression on post-stroke functional outcomes, brain injury and inflammatory mechanisms. Wild type (WT) and Bim-deficient mice underwent 1-h middle cerebral artery occlusion (MCAO) followed by 23 h of reperfusion. At 24-h post-stroke, we assessed functional deficit, infarct volume, immune cell death, as well as the number of infiltrating immune cells in the brain and circulating immune cells. Bim deficiency did not affect infarct volume (P > 0.05), but resulted in less motor impairment (~ threefold greater latency to fall in hanging grip strength test, P < 0.05) and a lower median clinical score than WT mice (P < 0.05). Additionally following MCAO, Bim-deficient mice exhibited fewer myeloid cells (particularly neutrophils) in the ischemic brain hemisphere and less apoptosis of CD3+ T cells in the spleen and thymus compared with WT (all P < 0.05). After MCAO, Bim-deficient mice also tended to have more M2-polarised macrophages in the brain than WT mice. In sham-operated mice, we found that Bim deficiency resulted in greater numbers of circulating total CD45+ leukocytes, Ly6Clo+ monocytes and CD3+ T cells, although MCAO did not affect the number of circulating cells at 24 h in either genotype. Our findings suggest that Bim deficiency modulates post-stroke outcomes, including reductions in motor impairment, brain inflammation and systemic post-stroke leukocyte apoptosis. Bim could therefore serve as a potential therapeutic target for stroke.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39608182","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: 3

Neuroinflammatory Modulation of Extracellular Vesicle Biogenesis and Cargo Loading. 细胞外囊泡生物发生和货物装载的神经炎症调节。

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2022-12-01 Epub Date: 2022-02-18 DOI: 10.1007/s12017-022-08704-3

Jereme G Spiers, Natasha Vassileff, Andrew F Hill

引用次数: 5