RESUMO
Taraxasterol is one of the bioactive triterpenoids found in dandelion, a member of the family Asteraceae. In the animal or cellular models of several ailments, including liver damage, gastritis, colitis, arthritis, pneumonia, tumors, and immune system diseases, taraxasterol has been shown to have significant preventive and therapeutic effects. This review aims to evaluate the current state of research and provide an overview of the possible applications of taraxasterol in various diseases. The reported phytochemical properties and pharmacological actions of taraxasterol, including anti-inflammatory, anti-oxidative, and anti-carcinogenic properties, and its potential molecular mechanisms in developing these diseases are highlighted. Finally, we further explored whether taraxasterol has protective effects on neuronal death in neurodegenerative diseases. In addition, more animal and clinical studies are also required on the metabolism, bioavailability, and safety of taraxasterol to support its applications in pharmaceuticals and medicine.
RESUMO
Isolated congenital coronary artery fistula (ICCAF) is an exceedingly rare anomaly in which there is a direct abnormal connection between a coronary artery and other cardiac chambers or any of great vessels. The left circumflex artery (LCX) is the least common source of ICCAF. Here we reported a rare case of large ICCAF originated from the LCX in a 9-year-old boy. He presented fatigability, murmurs and NYHA class II. Echocardiography and cardiac CT revealed that an aneurysmal dilatation of the LCX along with the dilated coronary sinus entered into the right atrium (RA) through the great cardiac vein. However, it showed that the dilated LCX directly drained into the RA by coronary angiography, which was confirmed by the surgery. During the surgical procedure, the LCX fistula was identified in a 3*3 cm bulbous structure, the aneurysmal dilation of RA tissue. The end of fistula was located in the lower-middle interatrial septum, which was near the coronary sinus and above the opening of inferior vena cava (IVC). Transcardiac chamber closure with cardiopulmonary bypass (CPB) was successfully performed for the correction of the fistula. It indicated that preoperative angiography is essential to define the details of large ICCAF with aneurysmal dilation. Moreover, transcardiac chamber closure with CPB is the optimal procedure for the treatment of large ICCAF, while interventional catheterization is not feasible due to the presence of aneurysmal dilation of the LCX. The description of this rare case might have great value for the diagnosis and treatment of large ICCAF originated from the LCX.
RESUMO
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson's disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD. Thus, we addressed the relationship between CDK5 and GP78 in MPTP-based PD models. We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78. Importantly, overexpression of GP78 or interference of GP78 Ser516 phosphorylation protected neurons against MPP+-induced cell death. Thus, our research reveals that the CDK5-GP78 pathway is involved in the pathogenesis of PD and could be a novel candidate drug target for the treatment of PD.
Assuntos
Morte Celular/fisiologia , Quinase 5 Dependente de Ciclina/metabolismo , Neurônios/metabolismo , Doença de Parkinson Secundária/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Animais , Linhagem Celular , Neurônios/patologia , Doença de Parkinson Secundária/patologia , Fosforilação , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , UbiquitinaçãoRESUMO
Parkinson's disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP+-treated neurons. Furthermore, XBP1s was identified as a substrate of CDK5 and that the phosphorylation of XBP1s at the Ser61 residue enhances its nuclear migration, whereas mutation of the residue to alanine substantially reduces its nuclear translocation and activity. Importantly, phosphorylated XBP1s acts as a nuclear transcription factor for multiple target genes, including metabolic-related genes, FosB, and non-coding RNAs. Our findings confirm that the IRE1α/XBP1 pathway is activated in PD, and reveal a novel role of XBP1s in the pathogenesis of PD. This pathway may be a new therapeutic strategy for PD.