Metabolic brain disease最新文献

{"title":"Uncovering the therapeutic efficacy and mechanisms of Quercetin on traumatic brain injury animals: a meta-analysis and network pharmacology analysis.","authors":"Yawen Cai, Xiaohang Zhang, Haotian Qian, Guiqin Huang, Tianhua Yan","doi":"10.1007/s11011-024-01449-x","DOIUrl":"https://doi.org/10.1007/s11011-024-01449-x","url":null,"abstract":"<p><p>Quercetin, a flavonoid and natural antioxidant derived from fruits and vegetables, has shown promising results in the improvement of traumatic brain injury (TBI). This study aims to elucidate the therapeutic role and potential mechanisms of quercetin in TBI through systematic evaluations and network pharmacology approaches. First, the meta-analysis was conducted via Review Manager 5.4 software. The meta-analysis results confirmed that quercetin could improve TBI, primarily by inhibiting inflammation, oxidative stress, and apoptosis. Subsequently, targets related to quercetin and those related to TBI were extracted from drug-related databases and disease-related databases, respectively. We found that the potential mechanism by which quercetin treats TBI is largely associated with ferroptosis, as indicated by functional analysis. Based on this, we identified 29 ferroptosis-related genes (FRGs) associated with quercetin and TBI, and then performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using the DAVID database. The functional enrichment results revealed that these FRGs mainly involve the HIF-1 signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. Subsequently, we constructed a PPI network and identified the top 10 targets-HIF1A, IL6, JUN, TP53, IL1B, PTGS2, PPARG, EGFR, IFNG, and GSK3B-as hub targets. Meanwhile, molecular docking results further demonstrated that quercetin could stably bind to the top 10 hub targets. In conclusion, the above results elucidated that quercetin could effectively attenuates TBI by inhibiting inflammation, oxidative stress, and apoptosis. Notably, quercetin may also target these hub targets to regulate ferroptosis and improve TBI.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise rescues cognitive impairment through inhibiting the fibrinogen neuroinflammative pathway in diabetes.","authors":"Dongwei Lu, Chujie Qu, Mei Fang, Junjian Zhang","doi":"10.1007/s11011-024-01455-z","DOIUrl":"https://doi.org/10.1007/s11011-024-01455-z","url":null,"abstract":"<p><p>Fibrinogen is a pivotal factor in the activation of neuroinflammation and cognitive impairment. While exercise, especifically swimming, has demonstrated cognitive benefits, the molecular protective mechanisms orchestrated by exercise in response to blood-brain barrier (BBB) leakage in diabetes remain elusive. This study systematically investigates the impact of fibrinogen on neuroinflammation and the role of exercise in diabetic rats. Diabetic rats underwent an 8-week swimming exercise regimen, and subsequent assessments included changes in interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), astroglia activation, BBB permeability, and key epithelial tight junction proteins such as zona occludins (ZO)-1, Claudin-5, and matrix metalloproteinase-9 (MMP-9). Spatial learning and memory were evaluated using the Morris water maze test and the novel object recognition test. The study revealed that exercise significantly improved cognitive function, potentially by suppressing fibrinogen levels and astroglia activation. Intriguingly, heightened fibrinogen expression markedly attenuated the protective effects of exercise on BBB integrity. Fibrinogen emerged as a potential compromise to exercise protective effect by increasing expression levels of inflammatory factors IL-1β and TNF-α. In summary, our findings elucidate that fibrinogen may contribute to the deterioration of cognition and diminish the protective effects of exercise by amplifying the neuroinflammatory process through damaged BBB in diabetes.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats dependent on NLRP3 activation.","authors":"Sandra Bonfante, Martins Back Netto, Aloir Neri de Oliveira Junior, Khiany Mathias, Richard Simon Machado, Larissa Joaquim, Taina Cidreira, Marina Goulart da Silva, Guilherme Cabreira Daros, Lucinéia Gainski Danielski, Fernanda Gava, Isabela da Silva Lemos, Rafaela Tezza Matiola, Emily Córneo, Josiane Somariva Prophiro, Rafael Mariano de Bitencourt, Carlos Henrique Rocha Catalão, Jaqueline da Silva Generoso, Emílio Luiz Streck, Felipe Dal-Pizzol, Tatiana Barichello, Fabricia Petronilho","doi":"10.1007/s11011-024-01425-5","DOIUrl":"https://doi.org/10.1007/s11011-024-01425-5","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposed for communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats. Adult or aged male Wistar rats were subjected to the TF model and received intracerebroventricular saline or MCC950 (140 ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival. The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration. The administration of MCC950 restored memory, IL-1β and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex were reversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}