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Abstract Background Targeting mitochondrial dynamics offers promising strategies for treating glioblastoma multiforme. Celastrol has demonstrated therapeutic effects on various cancers, but its impact on mitochondrial dynamics in glioblastoma multiforme remains largely unknown. We studied the effects of Celastrol on mitochondrial dynamics, redox homeostasis, and the proliferation. Methods Mito-Tracker Green staining was conducted on U251, LN229, and U87-MG cells to evaluate the effects of Celastrol on mitochondrial dynamics. The Western blot analysis quantified the expression levels of mitochondrial dynamin, antioxidant enzymes, and cell cycle-related proteins. JC-1 staining was performed to discern mitochondrial membrane potential. Mitochondrial reactive oxygen species were identified using MitoSOX. The proliferative capacity of cells was assessed using Cell Counting Kit-8 analysis, and colony formation assays. Survival analysis was employed to evaluate the therapeutic efficacy of Celastrol in C57BL/6J mice with glioblastoma. Results Our findings suggest that Celastrol (1 and 1.5 µM) promotes mitochondrial fission by downregulating the expression of mitofusin-1. A decrease in mitochondrial membrane potential at 1 and 1.5 µM indicates that Celastrol impaired mitochondrial function. Concurrently, an increase in mitochondrial reactive oxygen species and impaired upregulation of antioxidant enzymes were noted at 1.5 µM, indicating that Celastrol led to an imbalance in mitochondrial redox homeostasis. At both 1 and 1.5 µM, cell proliferation was inhibited, which may be related to the decreased expression levels of Cyclin-dependent kinase 1 and Cyclin B1. Celastrol extended the survival of GBM-afflicted mice. Conclusion Celastrol promotes mitochondrial fission in glioblastoma multiforme cells by reducing mitofusin-1 expression, accompanying mitochondrial dysfunction, lower mitochondrial membrane potential, heightened oxidative stress, and decreased Cyclin-dependent kinase 1 and Cyclin B1 levels. This indicates that Celastrol possesses potential for repurposing as an agent targeting mitochondrial dynamics in glioblastoma multiforme, warranting further investigation.

Abstract Background This study aimed to identify the risk factors for hemorrhage from a large cohort who underwent stereotactic needle biopsy for brain lesions at a single center over a 10-year period. Methods We performed a retrospective chart review of consecutive patients who underwent stereotactic biopsy at our institute between January 2010 and December 2019. Demographic characteristics and clinical variables were collected and analyzed to identify risk factors for postbiopsy hemorrhage using the chi-square test and univariable and multivariable logistic regression analyses. Results A total of 3196 patients were included in this study; of these, a histological diagnosis was eventually made for 2938 (91.93%) patients. Hemorrhage occurred in 149 (4.66%) patients, and symptomatic hemorrhage occurred in 46 (1.44%) patients. In multivariable logistic regression analyses, the presence of deep-seated lesions (OR 1.272, p = 0.035), concomitant edema and enhancement on MR imaging scans (OR 1.827, p = 0.002), intraoperative hypertension without a past history (OR 1.012, p = 0.024), and the presence of high-grade glioma (OR 0.306, p = 0.003) were identified as independent predictors of hemorrhage after biopsy. Conclusion Stereotactic needle biopsy is a safe and effective way to obtain tissue from brain lesions for histological diagnosis. The presence of deep-seated lesions, concomitant edema, and enhancement on MR imaging scans and the presence of high-grade glioma are independent predictors of hemorrhage after stereotactic biopsy.

ObjectiveTo track the clinical outcomes in patients who initially presented with tumefactive demyelinating lesions (TDLs), we summarized the clinical characteristics of various etiologies, and identified possible relapse risk factors for TDLs.MethodsBetween 2001 and 2021, 116 patients initially presented with TDLs in our hospital were retrospectively evaluated. Patients were followed for relapse and clinical outcomes, and grouped according to various etiologies. Demographic information, clinical data, imaging data, and laboratory results of patients were obtained and analyzed. The risk factors of relapse were analyzed by the Log-Rank test and the Cox proportional hazard model in multivariate analysis.ResultDuring a median follow-up period of 72 months, 33 patients were diagnosed with multiple sclerosis (MS), 6 patients with Balo, 6 patients with neuromyelitis optica spectrum disorders (NMOSD), 10 patients with myelin oligodendrocyte glycoprotein antibody-associated demyelination (MOGAD), 1 patient with acute disseminated encephalomyelitis (ADEM), and the remaining 60 patients still have no clear etiology. These individuals with an unknown etiology were categorized independently and placed to the other etiology group. In the other etiology group, 13 patients had recurrent demyelinating phases, while 47 patients did not suffer any more clinical events. Approximately 46.6% of TDLs had relapses which were associated with multiple functional system involvement, first-phase Expanded Disability Status Scale score, lesions morphology, number of lesions, and lesions location (P

Incorporating service composition and pervasive computing into managing users' complex everyday activities calls for the Pervasive Service Composition paradigm for everyday life. In this paper, we propose the concept of Context-Aware Pervasive Service Composition (CAPSC), which aims at enabling a pervasive system to provide user service compositions that are relevant to the situation at hand. We investigate CAPSC requirements and design a CAPSC architecture by taking into account context-aware peer coordination, context-aware process service adaptation, and context-aware utility service adaptation. We present a proof of concept application prototype as well. [ABSTRACT FROM AUTHOR]