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OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).
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Ressecção Transuretral da Próstata , Humanos , Masculino , Idoso , Ressecção Transuretral da Próstata/efeitos adversos , Proteômica , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/sangue , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/metabolismo , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/sangue , Período Perioperatório , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Biologia ComputacionalRESUMO
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).
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Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Recém-Nascido , Humanos , Hipóxia-Isquemia Encefálica/terapia , Transplante de Células-Tronco , Hipóxia , Neurônios , Hipotermia Induzida/métodosRESUMO
OBJECTIVE: To investigate effects of Shengmai injection (SMI) postconditioning on myocardial ischemia-reperfusion injury (MIRI) in isolated rat hearts. MATERIALS AND METHODS: A total of thirty isolated hearts were randomly divided into three groups: Sham group, I/R group and SMI group. Sham group was continuously perfused with K-H solution for 120 minutes. I/R group and SMI group were given balanced perfusion for 30 min followed by reperfusion for 60 min, with an interval of 30 min, and those in the SMI group were given postconditioning with 1% SMI during the first 10 min of reperfusion. The left ventricular function, markers of myocardial injury, endothelial cell injury and oxidative stress injury were measured at 30 minutes after equilibration (t0), 30 minutes after ischemia (t2) and 60 minutes after reperfusion (t3). RESULTS: The results showed that there was no significant difference for all observation indexes at t0. Compared with the Sham group, real portfolio project and coronary arterial flow rate and the activity of superoxide dismutase were significantly decreased in the I/R group, whereas those in the SMI group were significantly higher. Left ventricular end-diastolic pressure, the concentrate of malondialdehyde, lactate dehydrogenase, cTn-I, hyaluronic acid, heparin sulphate, syndecan-1 in the I/R group were markedly higher than those in the Sham group, whereas those in the SMI group were significantly lower. CONCLUSION: In summary, the present study indicated that 1% SMI postconditioning can alleviate the detachment of endothelial cell glycoprotein envelope induced by myocardial ischemia-reperfusion injury, and its mechanism is probably related to the inhibition of the oxidative stress injury.
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Traumatismo por Reperfusão Miocárdica , Animais , Combinação de Medicamentos , Medicamentos de Ervas Chinesas , Células Endoteliais , Glicoproteínas , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio , Ratos , Ratos Sprague-DawleyRESUMO
Even after successful hip arthroplasty, elderly patients who have undergone this procedure remain subject to cognitive decline and may collectively develop postoperative cognitive dysfunction (POCD). However, no consensus exists as to the risk factors resulting in a higher likelihood that a patient may present with this complication, and the aetiology of POCD is not well understood. We conducted a systematic review of papers concerning the influence of POCD-related risk factors in patients undergoing hip arthroplasty but limited the literature search to papers in English. A systematic and electronic search for manuscripts in the PubMed database was performed in order to identify all studies in which the risk factors for POCD were investigated. Articles were also obtained from the authors' files. Keywords for the search were postoperative cognitive dysfunction/change/impairment/decline/deficit, elderly/older/aged patients, and hip arthroplasty/replacement surgery. The evidence published to date suggests that POCD is a multifactorial disease, which includes an individual patient's characteristics, surgery, type of anaesthesia, and pain levels. All of these factors can increase the risk of POCD incidence. There are a number of factors that appear to influence the risk of early cognitive dysfunction after hip arthroplasty. Nevertheless, the specific mechanism and explicit risk factors associated with this cognitive dysfunction are not completely understood. Hip arthroplasty has made it possible for older patients to find relief from pain and improve their function, whereas it also increases the risk for suffering POCD that may affect these patients' quality of life and increase their mortality. Therefore, it is worthwhile investigating the mechanism of POCD in future studies in order to prevent and treat this condition.
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Artroplastia de Quadril , Disfunção Cognitiva , Complicações Pós-Operatórias , Idoso , Artroplastia de Quadril/efeitos adversos , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Humanos , Incidência , Complicações Cognitivas Pós-Operatórias , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Qualidade de VidaRESUMO
The aim of this study was to identify related scientific outputs and emerging topics of stem cells in neonatal hypoxic-ischemic encephalopathy (NHIE) and cerebral palsy (CP) through bibliometrics and literature review. All relevant publications on stem cell therapy for NHIE and CP were screened from websites and analyzed research trends. VOSviewer and CiteSpace were applied to visualize and quantitatively analyze the published literature to provide objective presentation and prediction. In addition, the clinical trials, published articles, and projects of the National Natural Science Foundation of China associated with stem cell therapy for NHIE and CP were summarized. A total of 294 publications were associated with stem cell therapy for NHIE and CP. Most publications and citations came from the USA and China. Monash University and University Medical Center Utrecht produced the most publications. Pediatric research published the most studies on stem cell therapy for NHIE and CP. Heijnen C and Kavelaars A published the most articles. Cluster analyses show that current research trend is more inclined toward the repair mechanism and clinical translation of stem cell therapy for NHIE and CP. By summarizing various studies of stem cells in NHIE and CP, it is indicated that this research direction is a hot topic at present. Furthermore, organoid transplantation, as an emerging and new therapeutic approach, brings new hope for the treatment of NHIE and CP. This study comprehensively summarized and analyzed the research trend of global stem cell therapy for NHIE and CP. It has shown a marked increase in stem cell therapy for NHIE and CP research. In the future, more efforts will be made on exploring stem cell or organoid therapy for NHIE and CP and more valuable related mechanisms of action to achieve clinical translation as soon as possible.
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Bibliometria , Paralisia Cerebral , Hipóxia-Isquemia Encefálica , Transplante de Células-Tronco , Humanos , Hipóxia-Isquemia Encefálica/terapia , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/tendências , Paralisia Cerebral/terapia , Animais , Recém-NascidoRESUMO
Background: Gastrodin can reduce neuronal damage through multiple targets and pathways, and can be useful in preventing and treating degenerative lesions of the central nervous system, but the specific mechanism has not been elucidated. Methods: The aging-related genes in the hippocampus and the frontal cortex were detected in adult and aged mice treated with gastrodin or not. In addition, we collected the target genes of gastrodin and aging from a network database, and a Venn diagram was created to obtain the intersection target genes of gastrodin and aging. Then, the String database was used to analyze the protein-protein interactions (PPIs) between aging-related genes and the target genes of gastrodin and aging. The "drug-disease-target-pathway" network was constructed using Cytoscape 3.7.2 software, and the main mechanism and pathway of key genes were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Finally, the reliability of these key genes was further verified by molecular docking technology. Results: The results showed that 6 out of 10 genes related to brain aging were differentially expressed after gastrodin intervention. Moreover, there were 11 key genes between gastrodin and differentially expressed genes related to brain aging. GO and KEGG results suggested that material metabolism and carbohydrate digestion and absorption were associated with the pathological mechanism of gastrodin antiaging. Molecular docking results also confirmed the good binding activity of gastrodin to the key genes. Conclusion: Gastrodin plays a potential role in antiaging by regulating substance metabolism and carbohydrate digestion and absorption.
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Hypoxic-ischemic encephalopathy (HIE) is the leading cause of long-term neurological disability in neonates and adults. Through bibliometric analysis, we analyzed the current research on HIE in various countries, institutions, and authors. At the same time, we extensively summarized the animal HIE models and modeling methods. There are various opinions on the neuroprotective treatment of HIE, and the main therapy in clinical is therapeutic hypothermia, although its efficacy remains to be investigated. Therefore, in this study, we discussed the progress of neural circuits, injured brain tissue, and neural circuits-related technologies, providing new ideas for the treatment and prognosis management of HIE with the combination of neuroendocrine and neuroprotection.
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The objective of this study was to compare the efficiency of trypsin and papain in neuronal digestion and determine which enzyme is more efficient. Cortical tissues were obtained from Sprague-Dawley (SD) rats. According to the different digestive enzymes, the samples were divided into the trypsin group and the papain group. After being digested by each of the two enzymes, cortical neurons were collected from the samples. Then, the morphology of the cortical neurons was determined. Moreover, the cortical neurons were transfected with the negative control (NC) lentivirus. The transfection efficiency and morphology were determined and compared. Compared with the papain group, cortical neurons in the trypsin group were more in number, had larger cell size, had longer axonal length, and had fewer impurities. The transfection efficiency of the trypsin group (57.77%) was higher than that of the papain group (53.83%). The morphology of neurons that was displayed showed that the cell body of most neurons shrank and became smaller, and the axis mutation became shorter and less in the papain group 6 days after transfection with the NC lentivirus. Trypsin is more efficient in digesting neurons because the neurons digested by this enzyme are more in number, have a larger cell body, longer axons, and greater transfection efficiency.
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Huangqi Guizhi Wuwu Decoction (HGWD) has a definite effect on neuropathic pain (NP), whereas the specific mechanism has not been elucidated. The components and targets in HGWD were collected and identified through System Pharmacology Database (Traditional Chinese Medicine Database and Analysis Platform). Genecards and Online Mendelian Inheritance in Man databases were used to search for NP-related genes. The Venn diagram was drawn to get the intersection target. Cytoscape 3.8.0 software was used to construct the compound-disease-target-pathway networks. STRING database was applied to analyze protein-protein interaction of potential targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were used to identify the function of genes related to NP. Finally, molecular docking was performed to visualize the binding mode and affinity between proteins and active ingredients. According to the intersection target of the Venn diagram, the network graph is constructed by Cytoscape and the results show the five compounds, ß-sitosterol, (+)-catechin, quercetin, Stigmasterol, kaempferol, and 15 genes (CASP3, FOS, GSK3B, HSP90AA1, IKBKB, IL6, MAPK8, RELA, ICAM1, SELE, ELK1, HSPB1, PRKACA, PRKCA, RAF1) were highly correlated with NP. KEGG and GO of 15 genes results that TNF, IL-17 and MAPK signaling pathway were Significantly related to the pathological mechanism of NP. Molecular docking showed that core genes in this network were IL-6 (TNF and IL-17 signaling pathways), ICAM1 (TNF signaling pathway), and CASP3 (three signal pathways). This study found that the five active compounds, three core genes, and three signaling pathways may be the key to the treatment of NP by HGWD.
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BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication with high morbidity and mortality, commonly observed in the elderly who underwent anesthesia and surgery. The incidence is much higher in cardiac surgery. However, the reason and the mechanism of POCD remains unclear, but cerebral hypoxia is a common neurological complication after cardiac surgery. This study aims to investigate what role cerebral hypoxia plays in the pathogenesis of POCD. METHODS: The POCD model was established using cardiopulmonary bypass (CPB) surgery. Cognitive function was detected using Y maze and Morris water maze. The hypoxia in central nervous system was assessed using HE staining, western blot, and immunofluorescence. Inflammatory factors in hippocampus and plasma were detected by enzyme-linked immunosorbent assay. Evans blue was used to detect destruction of the blood brain barrier (BBB). RESULTS: Cognitive impairment markedly occurred to rats underwent 2-h CPB operation. Cerebral thrombosis and hypoxia occurred in the hippocampal CA3 region of rats after surgery. In addition, microglia in hippocampal was activated and the expression of inflammatory factors such as IL-1ß, IL-6 and TNF-α was upregulated. Moreover, the permeability of BBB increased in rats after CPB. CONCLUSION: Hypoxia in hippocampal CA3 region was involved in the occurrence and the mechanism may be associated with neuroinflammation and the damage of BBB.
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Hipóxia Encefálica , Complicações Cognitivas Pós-Operatórias , Idoso , Animais , Região CA3 Hipocampal , Ponte Cardiopulmonar/efeitos adversos , Humanos , Hipóxia , Hipóxia Encefálica/etiologia , Complicações Cognitivas Pós-Operatórias/etiologia , RatosRESUMO
PURPOSE: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. METHODS: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. RESULTS: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. CONCLUSIONS: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.
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Lesões Encefálicas Traumáticas , Fármacos Neuroprotetores , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Caspase 3 , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2RESUMO
OBJECTIVES: Understanding the occupational characteristics of patients is not only related to patients' life and health, but also conducive to improving their happiness. However, there were no studies that had been conducted on the relationship between occupation characteristic and postoperative recovery in patients with spinal fractures. The purpose of this study was to explore the relationship between the occupation characteristics of patients with thoracolumbar fracture and the characteristics of disease injury, treatment, and recovery so as to reduce the incidence and improve postoperative rehabilitation. METHODS: Patients (n = 719) with thoracolumbar fractures were recruited. Patients were grouped according to the characteristic of occupations: unemployed group (n = 299), white-collar worker group (n = 20), and blue-collar worker group (n = 400). Data were collected, including the characteristics, injury and treatment information, and the recovery records for 1 year after operation. One-way ANOVA analysis, χ2 test, and binary logistic regression analysis was used to explore the relationship among these factors. RESULTS: Male, high-falling injuries and single segment injury (mainly T 11, T 12 and L2) were common in patients with thoracolumbar fractures, especially in the blue-collar worker group (70.8%, 78.3%, and 85.4%). Compared with the unemployed group, the patients in the white-collar worker group and blue-collar worker group had a higher proportion of young patients, a higher height and weight, a lesser rate of hypertension or diabetes. One week after injury, 73.4% of patients underwent surgery, with the blue-collar worker group accounted for the largest proportion. One month after surgery, 77.1% of patients were able to get out of bed, with the white-collar worker group accounted for the largest proportion. In the postoperative recovery information, patients in the blue-collar worker group were more likely to have severe low back pain (OR = 2.023, 95% CI: 1.440-2.284) and pain-disturbed sleep (OR = 2.287, 95% CI: 1.585-3.299) than those who in the unemployed group. CONCLUSIONS: Blue-collar workers, with a high risk of thoracolumbar fracture, have a higher incidence of low back leg pain and pain-disturbed sleep in the recovery after thoracolumbar fracture surgery, and this requires more attention.
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Ocupações , Fraturas da Coluna Vertebral , Humanos , Incidência , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Dor , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgiaRESUMO
[This corrects the article DOI: 10.3389/fcell.2020.00577.].
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Perioperative neurocognitive disorder (PND) is recently recommended to define the cognitive decrease during the perioperative period. However, the disease's underlying mechanisms remain unclear. MicroRNAs (miRNAs) are noncoding RNAs that play a vital role in regulating neuroregeneration and neuronal apoptosis. In this study, miR-124-3p was significantly reduced in the PND rat model after a cardiopulmonary bypass (CPB) procedure. MicroRNA-124 (miR-124)-3p-overexpressed lentivirus was constructed and injected via the intracerebroventricular method before CPB. Morris Water Maze test (WMW) and the Open-Field test (OFT) were used to measure behavior changes, data shows decline of cognitive function of rats after CPB. PND rats expressed higher Aß and p-Tau Protein by using immunohistochemistry (IHC) analyses and Enzyme-Linked Immune Sorbent Assay (ELISA). Moreover, the results of IHC, ELISA, Western Blot analysis (WB) and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling Assay (TUNEL) showed CPB procedure induced inflammation and apoptosis in rats with PND. The data also revealed the protective function of miR-124-3p overexpression against PND in relieving inflammation, cell apoptosis, and alleviating repaired cognitive function. Moreover, miR-124-3p was predicted by directly targeting LPIN1. This study gives a novel viewpoint that miR-124-3p could improve the state of PND via modulating LPIN1, therefore providing a new strategy for preventing and treating PND in a preclinical application.
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Ponte Cardiopulmonar , MicroRNAs , Animais , Apoptose , Inflamação , Masculino , MicroRNAs/genética , Transtornos Neurocognitivos , RatosRESUMO
This study aimed to explore the application value of nalbuphine in pulsed radiofrequency operation of trigeminal ganglion in patients with postherpetic neuralgia (PHN). Thirty patients with PHN were randomly divided into the nalbuphine (Nalbu) group and ketorolac tromethamine (KT) group and received CT-guided pulsed radiofrequency surgery on trigeminal ganglion. The numeric rating scale (NRS) scores of patients were recorded at preoperative, intraoperative, and postoperative time points, before going to bed, and the next morning after the operation. In addition, the number of breakthrough pain before operation and within 24 hours after operation, the incidence of nausea and vomiting within 24 hours after surgery, and the patient's sleep quality before and on the day after surgery were evaluated. The outcome data demonstrated that patients treated with nalbuphine had lower NRS scores after the pulse radiofrequency operation during and after the pulse radiofrequency operation compared to those with KT. In addition, nalbuphine effectively decreased the number of breakthrough pain, reduced the occurrence of nausea and vomiting after surgery, and improved the sleep quality. In conclusion, intramuscular injection of nalbuphine 30 min before trigeminal ganglion pulse radiofrequency surgery can be conducive to pain relief and improve the postoperative comfort of patients, providing an effective alternative for the alleviation of PHN in clinic.
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Nalbufina/uso terapêutico , Neuralgia Pós-Herpética/tratamento farmacológico , Tratamento por Radiofrequência Pulsada/métodos , Neuralgia do Trigêmeo/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nalbufina/farmacologiaRESUMO
BACKGROUND: Perioperative neurocognitive disorders (PND) resulting from cardiac surgery is a complication with high morbidity and mortality. However, the pathogenesis is unknown. METHODS: For the sake of investigating the risk factors and mechanism of PND, we collected the characteristics and neurological scores of patients undergoing cardiac surgery in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and Affiliated Hospital of Southwest Medical University from Jan 1, 2016 to Dec 11, 2018. RESULTS: We found that age and left atrial thrombus are independent risk factors for PND after cardiac surgery. Furthermore, the serum of 29 patients was collected on the 7th day after cardiac surgery for detecting the expression of lncRNA-MYL2-2 and miR-124-3p. Increased lncRNA-MYL2-2 and decreased miR-124-3p in serum were associated with the decline of patients' cognition. CONCLUSIONS: LncRNA-MYL2-2 and miRNA-124-3p may jointly participate in the occurrence and development of PND after cardiac surgery. These important findings are advantaged to further understand the pathogenesis of PND and prevent it, provide new biomarkers for the diagnosis and monitoring of PND.
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Procedimentos Cirúrgicos Cardíacos , MicroRNAs , Transtornos Neurocognitivos , RNA Longo não Codificante , Biomarcadores , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , MicroRNAs/genética , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/etiologia , RNA Longo não Codificante/genéticaRESUMO
Neonatal hypoxic-ischemic encephalopathy (HIE) is major cause of neonatal death or long-term neurodevelopmental disabilities, which becomes a major practical problem currently in clinic. Whereas, its pathophysiology and underlying molecular mechanism is not clear. MicroRNAs are involved in the normal growth and development of neuronal cells. Herein, the objective of this research was to examine the roles of miR-410-3p in neurological deficits, neuronal injury and neuron apoptosis after hypoxic-ischemic and to explore its associated mechanisms. We established the hypoxic-ischemic brain damage (HIBD) model and oxygen glucose deprivation (OGD) model. Zea-longa score and TTC staining were used to detect the acute cerebral dysfunction after HIBD. QPCR verification exhibited notable downregulation of miR-410-3p expression at 24 h in rats after HIBD as well as that in PC12, SY5Y cells and primary cortical neurons post OGD. To further determine the function of miR-410-3p, lentivirus-mediated overexpression virus was applied in vivo and in vitro. Behavioral tests, including Morris water maze, open field test, Y maze test, neurological severity score and rotating rod test, were performed to evaluate long-term behavioral changes of rats at 1 month post HIBD. The results showed that the number of cells together with the axonal length were reduced post OGD. While the increase of cells number and the axonal length was measured after upregulating miR-410-3p. Meanwhile, miR-410-3p overexpression inhibited neuron apoptosis and enhanced neuronal survival. In addition, long-term motor and cognitive functions were remarkably recovered in HIBD rats with miR-410-3p overexpression. Together, miR-410-3p exerts a critical role in protecting neuronal growth as well as promoting motor and cognitive function recovery in neonatal rats subjected to HIBD. The current study therefore provides critical insights to develop the activator of miR-410-3p for the clinical treatment of HIBD in future clinic trial.
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Córtex Cerebral/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , MicroRNAs/biossíntese , Neurônios/metabolismo , Animais , Animais Recém-Nascidos , Córtex Cerebral/patologia , Feminino , Expressão Gênica , Humanos , Hipóxia Encefálica , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/patologia , Aprendizagem em Labirinto/fisiologia , MicroRNAs/genética , Neurônios/patologia , Células PC12 , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Spinal cord injury (SCI) is a fatal disease that can cause severe disability. Cortical reorganization subserved the recovery of spontaneous function after SCI, although the potential molecular mechanism in this remote control is largely unknown. Therefore, using proteomics analysis, RNA interference/overexpression, and CRISPR/Cas9 in vivo and in vitro, we analyzed how the molecular network functions in neurological improvement, especially in the recovery of motor function after spinal cord transection (SCT) via the remote regulation of cerebral cortex. We discovered that the overexpression of pyridoxal kinase (PDXK) in the motor cortex enhanced neuronal growth and survival and improved locomotor function in the hindlimb. In addition, PDXK was confirmed as a target of miR-339 but not miR-124. MiR-339 knockout (KO) significantly increased the neurite outgrowth and decreased cell apoptosis in cortical neurons. Moreover, miR-339 KO rats exhibited functional recovery indicated by improved Basso, Beattie, and Bresnehan (BBB) score. Furthermore, bioinformatics prediction showed that PDXK was associated with GAP43, a crucial molecule related to neurite growth and functional improvement. The current research therefore confirmed that miR-339 targeting PDXK facilitated neurological recovery in the motor cortex of SCT rats, and the underlying mechanism was associated with regulating GAP43 in the remote cortex of rats subjected to SCT. These findings may uncover a new understanding of remoting cortex control following SCI and provide a new therapeutic strategy for the recovery of SCI in future clinical trials.
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Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.
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Purpose: To explore the neuroprotective effects of Lutongkeli (LTKL) in traumatic brain injury (TBI) and detect the related mechanism. Methods: TBI model was established with LTKL administration (2 and 4 g/kg/d, p.o.). Motor function of rats was examined by Rotarod test. Nissl staining was used to show neuron morphology. Furthermore, the disease-medicine common targets were obtained with the network pharmacology and analyzed with Kyoto Encyclopedia of Genes and Genomes. Lastly, the predicted targets were validated by real-time polymerase chain reaction. Results: After LTKL administration, neural behavior was significantly improved, and the number of spared neurons in brain was largely increased. Moreover, 68 bioactive compounds were identified, corresponding to 148 LTKL targets; 2,855 genes were closely associated with TBI, of which 87 overlapped with the LTKL targets and were considered to be therapeutically relevant. Functional enrichment analysis suggested LTKL exerted its pharmacological effects in TBI by modulating multiple pathways including apoptosis, inflammation, etc. Lastly, we found LTKL administration could increase the mRNA level of Bcl-2 and decrease the expression of Bax and caspase-3. Conclusions: This study reported the neuroprotective effect of LTKL against TBI is accompanied with anti-apoptosis mechanism, which provides a scientific explanation for the clinical application of LTKL in the treatment of TBI.