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Objectives: Amidst rising global burden of depression and the associated challenges with conventional antidepressant therapies, there is a growing interest in exploring the efficacy and safety of alternative treatments. This study uses a Bayesian network meta-analysis to rigorously evaluate the therapeutic potential of Chinese herbal medicines in the treatment of depression, focusing on their comparative efficacy and safety against standard pharmacological interventions. Methods: Five databases (PubMed, Wanfang Data, EMBASE, CNKI, and the Cochrane Library) and grey literature were searched from inception to end of July 2023 to identify studies that assessed the efficacy and safety of Chinese herbal medicines in treating depression. The response rate, Hamilton Depression Scale (HAMD) scores, and rates of adverse events were assessed through both direct and indirect comparisons. Data extraction and risk of bias assessment were meticulously performed. Statistical analysis used Markov chain Monte Carlo methods, with effect size estimates provided as odd ratios and their 95% confidence intervals. Results: A total of 198 RCTs involving 8,923 patients were analyzed, assessing 17 Chinese herbal medicines. Surface Under the Cumulative Ranking results indicated that the top three treatments with the best response rate were possibly Guipiwan, Ease Pill, and Chaihu Jia Longgu Muli Decoction; the top three treatments on the reduction of HAMD scores were Chai Hu Shu Gan San, Xingnao Jieyu Decoction, and Xiaoyao Powder; and the top three treatments with the lowest adverse effects rates were Xiaoyao Powder, Alprazolam, and Xingnao Jieyu Decoction. Interestingly, commonly used synthetic drugs such as Fluoxetine, Escitalopram, Amitriptyline, Sertraline, Flupentixol and Melitracen, and Venlafaxine, not only appeared to be less effective than specific Chinese herbal medicines (Gan Mai Da Zao Decoction, Chaihu Jia Longgu Muli Decoction, Chai Hu Shu Gan San, Danzhi-Xiaoyao-San, and Xingnao Jieyu Decoction), but they were also related to substantially higher risk of adverse events. Conclusion: Our findings elucidate the promising therapeutic potential of Chinese herbal medicines as viable alternatives in the treatment of depression, with certain herbs demonstrating enhanced efficacy and safety profiles. The outcomes of this study advocate for the integration of these alternative modalities into contemporary depression management paradigms. However, it underscores the necessity for larger, methodologically robust trials to further validate and refine these preliminary findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023452109.
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OBJECTIVE: Ischemic stroke (IS) is one of the major diseases threatening human health and survival and a leading cause of acquired mortality and disability in adults. The aim of this study was to screen diagnostic features of IS and to explore the characteristics of immune cell infiltration in IS pathogenesis. METHODS: The microarray data of IS (GSE16561, GSE58294, GSE37587, and GSE124026) in the GEO database were merged after removing the batch effect. Then integrated bioinformatic analysis and machine-learning strategies were adopted to analyze the functional correlation and select diagnostic signatures. The WGCNA was used to identify the co-expression modules related to IS. The CIBERSORT algorithm was performed to assess the inflammatory state of IS and to investigate the correlation between diagnostic signatures and infiltrating immune cells. RESULTS: Functional analysis of dysregulated genes showed that immune response-regulating signaling pathway and pattern recognition receptor activity were enriched in the pathophysiology of IS. The turquoise module was identified as the significant module with IS. By using Lasso and SVM-RFE learning methods, we finally obtained four diagnostic genes, including LAMP2, CR1, CLEC4E, and F5. The corresponding results of AUC of ROC prediction model in training and validation cohort were 0.954 and 0.862, respectively. The immune cell infiltration analysis suggested that plasma cells, resting and activated NK cells, activated dendritic cells, memory B cells, CD8+ T cells, naïve CD4+ T cells, and resting mast cells may be involved in the development of IS. Additionally, these diagnostic signatures might be correlated with multiple immune cells in varying degrees. CONCLUSION: We identified four biologically relevant genes (LAMP2, CR1, CLEC4E, and F5) with diagnostic effects for IS, our results further provide novel insights regarding molecular mechanisms associated with various immune cells that related to IS for future investigations.
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Linfocitos T CD8-positivos , Accidente Cerebrovascular Isquémico , Humanos , Adulto , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/genética , Transducción de Señal , Algoritmos , Aprendizaje AutomáticoRESUMEN
Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological changes in AD patients occur up to 10-20 years before the emergence of clinical symptoms. Specific diagnosis and appropriate intervention strategies are crucial during the phase of mild cognitive impairment (MCI) and AD. The detection of biomarkers has emerged as a promising tool for tracking the efficacy of potential therapies, making an early disease diagnosis, and prejudging treatment prognosis. Specifically, multiple neuroimaging modalities, including magnetic resonance imaging (MRI), positron emission tomography, optical imaging, and single photon emission-computed tomography, have provided a few potential biomarkers for clinical application. The MRI modalities described in this review include structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy, and arterial spin labelling. These techniques allow the detection of presymptomatic diagnostic biomarkers in the brains of cognitively normal elderly people and might also be used to monitor AD disease progression after the onset of clinical symptoms. This review highlights potential biomarkers, merits, and demerits of different neuroimaging modalities and their clinical value in MCI and AD patients. Further studies are necessary to explore more biomarkers and overcome the limitations of multiple neuroimaging modalities for inclusion in diagnostic criteria for AD.
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BACKGROUND: Many clinical studies have reported a relatively high incidence of osteoporosis and fragility fractures in patients with Cushing syndrome (CS). However, few papers have investigated osteoporosis and CS in terms of pathogenesis, so this study explores the association between the 2 and predicts upstream micro-ribonucleic acids (miRNAs) through bioinformatics, which provides potential targets for simultaneous pharmacological interventions in both diseases and also provides a basis for pathological screening. METHODS: We used Genecards, Online Mendelian Inheritance in Man and Therapeutic Target Database databases to screen the targets of osteoporosis and Cushing syndrome; import target genes to Database for Annotation, Visualization and Integrated Discovery for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis; the intersecting genes were uploaded to Search Tool for the Retrieval of Genes and Genomes database to construct protein-protein interaction network; Cytoscape software was used to screen core genes, and Molecular Complex Detection module was used to analyze cluster modules; finally, the NetworkAnalyst data platform was used to predict the miRNAs that interact with core genes. RESULTS: The core genes of osteoporosis and Cushing syndrome were insulin, tumor necrosis factor, signal transducer and activator of transcription 3 (STAT3), interleukin-6, insulin-like growth factor 1, etc. A total of 340 upstream miRNAs including hsa-let-7a-5p, hsa-mir-30a-5p and hsa-mir-125b-5p were predicted. The biological processes involved include regulating the transcription of ribonucleic acid polymerase II promoter and participating in the transduction of cytokine signaling pathways, which focus on the binding of nerve system ligand, JAK-STAT signaling pathway, Rap1 signaling pathway, PI3K-Akt signaling pathway, etc. CONCLUSION: Osteoporosis and Cushing syndrome are closely related in terms of targets and molecular mechanisms. In this study, bioinformatics methods were used to identify their targets and mechanisms, providing potential targets for drug simultaneous regulation of the 2 diseases, and providing a new direction for exploring the relationship between diseases.
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Síndrome de Cushing , MicroARNs , Osteoporosis , Humanos , Biología Computacional/métodos , Síndrome de Cushing/complicaciones , Síndrome de Cushing/genética , Fosfatidilinositol 3-Quinasas , MicroARNs/genética , Osteoporosis/genéticaRESUMEN
BACKGROUND: The incidence of threatened abortion (TA) is increasing due to poor diet and living habits, which brings great pressure to pregnant women and their families. Huangqin-Baizhu herb pair recorded in ancient books of traditional Chinese medicine has been widely used in the treatment of TA with remarkable effect. In this study, we will use the network pharmacology method to predict the target and mechanism of Huangqin-Baizhu herb pair. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to screen the active components of Huangqin-Baizhu herb pair. Pubchem and Swiss Target Prediction databases were used to predict the action targets. Genecards, OMIM, and Drugbank databases were used to predict the related targets of TA. The intersection of drug target and disease target was selected and the intersection genes were uploaded to STRING database to construct protein-protein interaction network and conduct module analysis. Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which was imported into Cytoscape software to construct component-pathway-gene network and finally verified by molecular docking. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy. RESULTS: The main active components of the herb pair are baicalein, flavanone, and norwogonin, etc. The main targets are AKT1, VEGFA, STAT3, MAPK1, SRC, etc. Cluster module analysis shows that the targets are related to cell metabolism, immune regulation and hormone level regulation. There were 2073, 3169, and 161 KEGG pathways involved in the biological processes, cell components, and molecular functions of Gene Ontology analysis, respectively. The main KEGG pathways involved in the intervention were HIF1 signaling pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway. Molecular docking showed that the main active components of the herb pair were well combined with the key targets. CONCLUSIONS: In this study, 42 active components, 152 potential targets and 11 key targets of Huangqin-Baizhu herb pair for the treatment of TA were revealed, participating in multiple signaling pathways such as PI3K-Akt, providing a theoretical basis for further experimental research.
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Amenaza de Aborto , Medicamentos Herbarios Chinos , Amenaza de Aborto/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Embarazo , Proteínas Proto-Oncogénicas c-akt , Scutellaria baicalensisRESUMEN
Objective: As a chronic neurodegenerative disorder, Alzheimer's disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology. Methods: The expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples. Functional enrichment analysis was performed to reveal AD-associated biological functions and key pathways. Besides, we applied the Least Absolute Shrinkage Selection Operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analysis to screen potential diagnostic feature genes in AD, which were further tested in AD brains of the validation cohort (GSE5281). The discriminatory ability was then assessed by the area under the receiver operating characteristic curves (AUC). Finally, the CIBERSORT algorithm and immune cell infiltration analysis were employed to assess the inflammatory state of AD. Results: A total of 49 DEGs were identified. The functional enrichment analysis revealed that leukocyte transendothelial migration, cytokine receptor interaction, and JAK-STAT signaling pathway were enriched in the AD group. MAF basic leucine zipper transcription factor F (MAFF), ADCYAP1, and ZFP36L1 were identified as the diagnostic biomarkers of AD with high discriminatory ability (AUC = 0.850) and validated in AD brains (AUC = 0.935). As indicated from the immune cell infiltration analysis, naive B cells, plasma cells, activated/resting NK cells, M0 macrophages, M1 macrophages, resting CD4+ T memory cells, resting mast cells, memory B cells, and resting/activated dendritic cells may participate in the development of AD. Additionally, all diagnostic signatures presented different degrees of correlation with different infiltrating immune cells. Conclusion: MAFF, ADCYAP1, and ZFP36L1 may become new candidate biomarkers of AD, which were closely related to the pathogenesis of AD. Moreover, the immune cells mentioned above may play crucial roles in disease occurrence and progression.
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BACKGROUND: In recent years, clinical studies have found that there is a close relationship between osteoporosis and polycystic ovary syndrome. However, there are few literature on the pathogenesis of osteoporosis and polycystic ovary syndrome. In order to clarify their common pathogenic mechanism and provide potential targets for drugs to regulate them at the same time, bioinformatics methods are used to explore, so as to provide a new direction for the study of the relationship between diseases in the future. METHODS: To screen the targets of osteoporosis and polycystic ovary syndrome by Genecards, Online Mendelian Inheritance in Man databases and Therapeutic Target Database to take the intersection of the two mappings and upload the intersection targets to the STRING database to construct protein-protein interaction network; to screen the core targets by degree value and import them to Metascape database for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis; and finally, to construct the visualization network of core targets and pathways by Cytoscape software. Ethical approval and informed consent of patients are not required because the data used in this study is publicly available and does not involve individual patient data or privacy. RESULTS: The core targets of polycystic ovary syndrome and osteoporosis were insulin gene, insulin-like growth factor 1, CTNNB1, serine/threonine kinase 1, signal transducer and activator of transcription 3, LEP, etc. The biological processes involved include the regulation of protein phosphorylation, cell proliferation and differentiation, hormone endocrine, reproductive system and skeletal system. The related pathways were concentrated in Foxo signaling pathway, HTLV-I infection, PI3K-AKT signaling pathway, MAPK signaling pathway and AGE-RAGE signaling pathway in diabetic complications. CONCLUSIONS: There is a close relationship between osteoporosis and polycystic ovary syndrome in terms of target and molecular mechanism. This study used bioinformatics to clarify their targets and mechanisms, providing potential targets for drugs to regulate both diseases simultaneously and providing new directions to explore the relationship between the diseases.
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Medicamentos Herbarios Chinos , Osteoporosis , Síndrome del Ovario Poliquístico , Biología Computacional , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genéticaRESUMEN
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and a CD4+ T cell-mediated autoimmune disease. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is recognized as the major mechanism that regulates the differentiation and function of T helper (Th) 1 and Th17 cells, which are recognized as pivotal effector cells responsible for the development of EAE. We used baricitinib, a JAK 1/2 inhibitor, to investigate the therapeutic efficacy of inhibiting the JAK/STAT pathway in EAE mice. Our results showed that baricitinib significantly delayed the onset time, decreased the severity of clinical symptoms, shortened the duration of EAE, and alleviated demyelination and immune cell infiltration in the spinal cord. In addition, baricitinib treatment downregulated the proportion of interferon-γ+CD4+ Th1 and interleukin-17+CD4+ Th17 cells, decreased the levels of retinoic acid-related orphan receptor γ t and T-bet mRNA, inhibited lymphocyte proliferation, and decreased the expression of proinflammatory cytokines and chemokines in the spleen of mice with EAE. Furthermore, our results showed the role of baricitinib in suppressing the phosphorylation of STATs 1, 3, and 4 in the spleen of EAE mice. Therefore, our study demonstrates that baricitinib could potentially alleviate inflammation in mice with EAE and may be a promising candidate for treating MS.
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Azetidinas/farmacología , Encefalomielitis Autoinmune Experimental/prevención & control , Quinasas Janus/antagonistas & inhibidores , Purinas/farmacología , Pirazoles/farmacología , Factores de Transcripción STAT/inmunología , Transducción de Señal/efectos de los fármacos , Sulfonamidas/farmacología , Administración Oral , Animales , Azetidinas/administración & dosificación , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/inmunología , Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Quinasas Janus/inmunología , Quinasas Janus/metabolismo , Ratones Endogámicos C57BL , Purinas/administración & dosificación , Pirazoles/administración & dosificación , Factores de Transcripción STAT/metabolismo , Transducción de Señal/inmunología , Sulfonamidas/administración & dosificaciónRESUMEN
BACKGROUND: Neuroinflammation and immune responses occurring minutes to hours after stroke are associated with brain injury after acute ischemic stroke (AIS). PPARγ coactivator-1α (PGC-1α), as a master coregulator of gene expression in mitochondrial biogenesis, was found to be transiently upregulated in microglia after AIS. However, the role of microglial PGC-1α in poststroke immune modulation remains unknown. METHODS: PGC-1α expression in microglia from human and mouse brain samples following ischemic stroke was first determined. Subsequently, we employed transgenic mice with microglia-specific overexpression of PGC-1α for middle cerebral artery occlusion (MCAO). The morphology and gene expression profile of microglia with PGC-1α overexpression were evaluated. Downstream inflammatory cytokine production and NLRP3 activation were also determined. ChIP-Seq analysis was performed to detect PGC-1α-binding sites in microglia. Autophagic and mitophagic activity was further monitored by immunofluorescence staining. Unc-51-like autophagy activating kinase 1 (ULK1) expression was evaluated under the PGC-1α interaction with ERRα. Finally, pharmacological inhibition and genomic knockdown of ULK1 were performed to estimate the role of ULK1 in mediating mitophagic activity after ischemic stroke. RESULTS: PGC-1α expression was shortly increased after ischemic stroke, not only in human brain samples but also in mouse brain samples. Microglia-specific PGC-1α overexpressing mice exhibited significantly decreased neurologic deficits after ischemic injury, with reduced NLRP3 activation and proinflammatory cytokine production. ChIP-Seq analysis and KEGG pathway analysis revealed that mitophagy was significantly enhanced. PGC-1α significantly promoted autophagic flux and induced autolysosome formation. More specifically, the autophagic clearance of mitochondria was enhanced by PGC-1α regulation, indicating the important role of mitophagy. Pharmacological inhibition or knockdown of ULK1 expression impaired autophagic/mitophagic activity, thus abolishing the neuroprotective effects of PGC-1α. CONCLUSIONS: Mechanistically, in AIS, PGC-1α promotes autophagy and mitophagy through ULK1 and reduces NLRP3 activation. Our findings indicate that microglial PGC-1α may be a promising therapeutic target for AIS.
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Lesiones Encefálicas/patología , Isquemia Encefálica/metabolismo , Encéfalo/patología , Inflamación/patología , Microglía/metabolismo , Fármacos Neuroprotectores/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Anciano de 80 o más Años , Animales , Autofagia , Homólogo de la Proteína 1 Relacionada con la Autofagia/antagonistas & inhibidores , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Secuencia de Bases , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/genética , Isquemia Encefálica/complicaciones , Isquemia Encefálica/genética , Isquemia Encefálica/patología , Línea Celular , Femenino , Perfilación de la Expresión Génica , Genoma , Humanos , Inflamación/complicaciones , Inflamación/genética , Integrasas/metabolismo , Masculino , Ratones Endogámicos C57BL , Microglía/patología , Microglía/ultraestructura , Mitofagia , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factores de Tiempo , Transcripción GenéticaRESUMEN
Objective: Neuroinflammation is a central part of cerebral ischemia/reperfusion injury. The novel immune suppressant, fingolimod, is a promising candidate to ameliorate stroke-induced damage. Fingolimod is efficacious in experimental ischemic models, but a rigorous meta-analysis is lacking that considers how different experiment variables affect outcomes.Methods: We conducted a systematic literature review of fingolimod in stroke models, with the aim of rigorously evaluating fingolimod's effects on reducing infarct volume improving neurological outcomes. Seventeen variables were evaluated as covariates for the source of heterogeneity, and effect sizes were combined by using normalized mean difference meta-analysis to evaluate efficacy. Study quality was evaluated by the CAMARADES ten-item checklist, and publication bias was evaluated by funnel plots and Egger's tests.Results: About 123 unduplicated articles were identified in the literature research. Of these papers, 118 articles were excluded after reading titles and abstracts. Another 17 articles were selected in this study. Study quality was moderate (median = 6; interquartile range = 4), and publication bias was statistically insignificant. fingolimod reduced infarct volume by 30.4% (95% CI 22.4%-38.3%; n = 24; I2 = 90.0%; p < 0.0001) and consistently enhanced neurobehavioral outcome by 34.2% (95% CI 23.1%-45.2%; n = 14; I2 = 76.5%; p < 0.0001). No single factors accounted for heterogeneity.Conclusions: Our rigorous statistical evaluation confirmed the neuroprotective properties of fingolimod. New data can be used in designing future clinical trials.
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Modelos Animales de Enfermedad , Clorhidrato de Fingolimod/uso terapéutico , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Receptores de Esfingosina-1-Fosfato/agonistas , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Clorhidrato de Fingolimod/farmacología , Humanos , Moduladores de los Receptores de fosfatos y esfingosina 1/farmacología , Receptores de Esfingosina-1-Fosfato/fisiología , Accidente Cerebrovascular/patología , Resultado del TratamientoRESUMEN
Cytosolic double-stranded DNA (dsDNA) is a danger signal that is tightly monitored and sensed by nucleic acid-sensing pattern recognition receptors. We study the inflammatory cascade on dsDNA recognition and investigate the neuroprotective effect of cyclic GMP-AMP (cGAMP) synthase (cGAS) antagonist A151 and its mechanisms of neuroprotection in a mouse model of experimental stroke. Here, we found that cerebral ischemia promoted the release of dsDNA into the cytosol, where it initiated inflammatory responses by activating the cGAS. A151 effectively reduced the expression of cGAS, absent in melanoma 2 (AIM2) inflammasome, and pyroptosis-related molecules, including caspase-1, gasdermin D, IL-1ß, and IL-18. Furthermore, mice treated with A151 showed a dampened immune response to stroke, with reduced counts of neutrophils, microglia, and microglial production of IL-6 and TNF-α after MCAO. Moreover, A151 administration significantly reduced infarct volume, attenuated neurodeficits, and diminished cell death. Notably, the protective effect of A151 was blocked in a microglia-specific cGAS knockout mouse. These findings offer unique perspectives on stroke pathogenesis and indicate that inhibition of cGAS could attenuate brain inflammatory burden, representing a potential therapeutic opportunity for stroke.
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Isquemia Encefálica , ADN , Accidente Cerebrovascular Isquémico , Neuroprotección , Nucleotidiltransferasas/metabolismo , Animales , Citosol , Inflamación , Ratones , Nucleotidiltransferasas/antagonistas & inhibidoresRESUMEN
Rationale: Mitochondrial dysfunction and oxidative stress occur in vascular dementia (VaD), but the specific molecular mechanism regulating these events remains unclear. Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a master regulator for mitochondrial function. This study aims to investigate whether PGC-1α is involved in the pathophysiology of VaD. Methods: We firstly generated PGC-1αf/f Eno2-Cre mice to induce neuron-specific overexpression of PGC-1α by crossbreeding PGC-1αf/f mice with Eno2-cre mice. Then, the mice were subjected to bilateral common carotid artery stenosis to induce chronic cerebral hypoperfusion. Neurological function and hippocampal PGC-1α expression was evaluated. Next, RNA-Seq analysis and Seahorse assay were performed on the hippocampal neurons. In addition, mitochondrial antioxidants, uncoupling proteins, ROS production and the activation of glial cells were also measured. Results: Our results showed that hippocampal PGC-1α expression is down-regulated in the mouse VaD model induced by chronic cerebral hypoperfusion. In contrast, neuronal PGC-1α overexpression significantly ameliorated cognitive deficits. RNA-Seq analysis indicated that PGC-1α improved energy metabolism of neurons under hypoxic condition, and Seahorse assay confirmed that PGC-1α increases the metabolic activity of neurons. Further study demonstrated that PGC-1α boosted the expressions of mitochondrial antioxidants and uncoupling proteins (UCPs), including SOD2, Prx3, GPx1, UCP2, UCP4 and UCP5, which in turn reduced reactive oxygen species (ROS) production. Moreover, the activation of microglia and astrocytes was also found to decrease in the hippocampus. All of these changes greatly contributed to protect hippocampal neurons against ischemic insults. Conclusions: PGC-1α could suppress the excessive ROS and neuroinflammation in the hippocampus, opening up a potential therapeutic target for cognitive impairment.
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Disfunción Cognitiva/metabolismo , Demencia Vascular/metabolismo , Hipocampo/metabolismo , Mitocondrias/metabolismo , Neuronas/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/fisiología , Animales , Línea Celular , Modelos Animales de Enfermedad , Hipocampo/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Reactive oxygen species (ROS) generation and mitochondrial dysfunction are related to neuron loss in multiple sclerosis (MS). Although peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) appears to play a key role in modulating levels of mitochondrial ROS, antioxidants, and uncoupling proteins (UCPs), and PGC-1α expression is reduced in the neocortex of patients with MS, it is unclear what its role is in neurons and in the manifestation of clinical symptoms of MS. Here, we show in wild-type (WT) experimental autoimmune encephalomyelitis (EAE) mice that PGC-1α is decreased 13 d after EAE induction followed by a steady decline up to 20 d. These changes were accompanied by parallel alterations in levels of superoxide dismutase 2, peroxiredoxin 3, thioredoxin 2, UCP4, and UCP5. In transgenic (TG) mice with neuron-specific overexpression of PGC-1α (PGC-1αf/fEno2-Cre), clinical symptoms after EAE induction were delayed and less severe than in WT mice. The degrees of apoptotic neuron loss and demyelination were also less severe in PGC-1α-TG mice. Overexpression of PGC-1α in neuronal neuroblastoma spinal cord 34 cells subjected to EAE inflammatory conditions showed similar results to those obtained in vivo. RNA sequencing analysis showed that apoptotic processes were significantly enriched in the top 10 significant gene ontology (GO) terms of differentially expressed genes, and the apoptotic pathway was significantly enriched in Kyoto Encyclopedia of Genes and Genomes pathway analysis. Our findings indicate that up-regulation of neuronal PGC-1α protected neurons from apoptosis in EAE. Manipulating PGC-1α levels in MS may help stave off this devastating disease.-Dang, C., Han, B., Li, Q., Han, R., Hao, J. Up-regulation of PGC-1α in neurons protects against experimental autoimmune encephalomyelitis.
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Apoptosis , Encefalomielitis Autoinmune Experimental/metabolismo , Neuronas/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Regulación hacia Arriba , Animales , Línea Celular Tumoral , Células Cultivadas , Encefalomielitis Autoinmune Experimental/genética , Femenino , Ratones , Ratones Endogámicos C57BL , Proteínas Desacopladoras Mitocondriales/genética , Proteínas Desacopladoras Mitocondriales/metabolismo , Peroxiredoxina III/genética , Peroxiredoxina III/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismoAsunto(s)
Isquemia Encefálica/complicaciones , Cognición , Demencia Vascular/complicaciones , Demencia Vascular/diagnóstico , Pruebas de Estado Mental y Demencia , Sustancia Blanca/patología , Anciano , Anisotropía , Isquemia Encefálica/sangre , Isquemia Encefálica/diagnóstico por imagen , Proteína C-Reactiva/metabolismo , Demencia Vascular/sangre , Demencia Vascular/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Tamaño de los Órganos , Sustancia Blanca/diagnóstico por imagenRESUMEN
A 74-year-old man with right upper eyelid swell accepted FDG PET/CT examination, which showed an intensely FDG-avid soft tissue nodular mass within the eyelid. It was suggestive of malignancy. There was no evidence of active neoplastic disease elsewhere. The nodule was excised by surgery. Histopathological findings showed characteristic findings of diffuse large B-cell lymphoma. This case highlights the utility of FDG PET/CT in identifying rare types of lymphoma.
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Neoplasias de los Párpados/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Linfoma/diagnóstico por imagen , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Anciano , Neoplasias de los Párpados/patología , Humanos , Linfoma/patología , MasculinoRESUMEN
Kimura disease is a chronic inflammatory disorder that occurs mainly in Asians. We present a patient with pulmonary Kimura disease assessed by whole-body 18F-FDG PET/CT examination and proved by pathologic findings. Chest x-ray detected left pulmonary hilum enlargement in a 49-year-old Chinese man. CT showed a soft tissue mass with punctate calcifications in the left pulmonary hilum, which obviously and homogeneously accumulated tracer on FDG PET. Histopathology findings showed characteristic of Kimura disease. Kimura disease should be included in the differential diagnosis of a pulmonary hilar tumor.
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Hiperplasia Angiolinfoide con Eosinofilia/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Pulmón/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Hiperplasia Angiolinfoide con Eosinofilia/cirugía , Reacciones Falso Positivas , Humanos , Masculino , Persona de Mediana Edad , ToracotomíaRESUMEN
Pulmonary mucormycosis is a life-threatening opportunistic mycosis that is difficult to diagnose early. We report the case of a 56-year-old woman who complained of intermittent fever in the afternoon and productive cough and pain on the right side of the chest. Her clinical condition deteriorated despite antibiotherapy. FDG PET/CT showed a heterogeneous soft tissue mass at the lower part of the right lung with obvious FDG uptake in the peripheral part of the mass. Mucormycosis was proven by histopathology and fungal culture from the transbronchial lung biopsy materials.
Asunto(s)
Fluorodesoxiglucosa F18 , Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Mucormicosis/diagnóstico por imagen , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Resultado Fatal , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Pulmón/patología , Enfermedades Pulmonares Fúngicas/patología , Persona de Mediana Edad , Mucormicosis/patologíaRESUMEN
The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, and human. This study identified 54 bHLH family members in the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae), genome. Phylogenetic analyses revealed that they belong to 37 bHLH families with 21, 13, 9, 1, 9, and 1 members in group A, B, C, D, E, and F, respectively. Through in-group phylogenetic analyses, all of the identified A. pisum bHLH members were assigned into their correspondent bHLH families with confidence, among which 51 were defined according to phylogenetic analyses with orthologs from Drosophila melanogaster Meigen (Diptera: Drosophilidae), and 3 of them were defined according to phylogenetic analyses with orthologs from Bombyx mori L. (Lepidoptera: Bombycidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Analyses on genomic coding regions revealed that the number and average length of introns in A. pisum bHLH motifs are higher than those in other insects. The present study provides useful background information for future studies on structure and function of bHLH proteins in the regulation of A. pisum development.