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Background and objectives: Endovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI. Methods: This is a retrospective cohort study of 297 consecutive patients with ischemic stroke who received EVT at three academic stroke centers in China from March 2019 to March 2022. Patient age, sex, modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), Alberta stroke program early CT score (ASPECTS), time to treatment, risk factors and comorbidities associated with cerebrovascular diseases were collected, and potential associations with futile recanalization were assessed. RFI was successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b without functional independence at 90 days (mRS ≥ 3). Results: Of the 297 initial patients assessed, 231 were included in the final analyses after the application of the inclusion and exclusion criteria. Patients were divided by those who had RFI (n = 124) versus no RFI (n = 107). Older age (OR 1.041, 95% CI 1.004 to 1.073; p = 0.010), chronic kidney disease (OR 4.399, 0.904-21.412; p = 0.067), and higher 24-h NIHSS (OR 1.284, 1.201-1.373; p < 0.001) were independent predictors of RFI. Conversely, an mTICI score of 3 was associated with a reduced likelihood of RFI (OR 0.402, 0.178-0.909; p = 0.029). Conclusion: In conclusion, increased age, higher 24-h NIHSS and lack of an mTICI score of 3 were independently associated with RFI and have potential prognostic values in predicting patients that are less likely to respond to EVT recanalization therapy.
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Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment. According to a recently published study in Science, copper death (cuproptosis) occurs when intracellular copper is overloaded, triggering aggregation of lipidated mitochondrial proteins and Fe-S cluster proteins. This intriguing phenomenon is triggered by the instability of copper ions. Understanding the molecular mechanisms behind cuproptosis and its associated genes, as identified by Tsvetkov, including ferredoxin 1, lipoic acid synthase, lipoyltransferase 1, dihydrolipid amide dehydrogenase, dihydrolipoamide transacetylase, pyruvate dehydrogenase α1, pyruvate dehydrogenase ß, metallothionein, glutaminase, and cyclin-dependent kinase inhibitor 2A, may open new avenues for cancer therapy. Here, we provide a new understanding of the role of copper death and related genes in cancer.
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths. The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism, including mitochondrial stress response. Mitokines, soluble proteins produced and secreted in response to mitochondrial stress, play an essential immunomodulatory role. Immunotherapy has emerged as a crucial treatment option for HCC. However, a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment. Therefore, exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy. This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function. In addition, a systematic review of mitokines-mediated immunomodulation in HCC is presented. Finally, the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized. Recent progress in mitokine research represents a new prospect for mitochondrial therapy. Considering the potential of mitokines to regulate immune function, investigating them as a relevant molecular target holds great promise for the diagnosis and treatment of HCC.
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Background and Aims: The growing knowledge of ferroptosis has suggested the regulatory role of ferroptosis in hepatocellular carcinoma (HCC), but the pertinent molecular mechanisms remain unclear. Herein, this study investigated the mechanistic basis of ferroptosis-related genes (ferrGenes) in the growth of HCC. Methods: Differentially expressed human ferrGenes and tumor-related transcription factors (TFs) were obtained from the The Cancer Genome Atlas (TCGA) dataset and the GTEx dataset. Spearman method-based correlation analysis were conducted to construct TF-ferrGene coexpression regulatory network. Key genes associated with prognosis were singled out with Lasso regression and multivariate Cox analysis to construct the prognostic risk model. Then the accuracy and independent prognostic ability of the model were evaluated. Expression of CENPA and STMN1 was determined in clinical HCC tissues and HCC cells, and their binding was analyzed with dual-luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, ectopic expression and knockdown assays were performed in HCC cells to assess the effect of CENPA and STMN1 on ferroptosis and malignant phenotypes. Results: The prognostic risk model constructed based on the eight TF-ferrGene regulatory network-related genes accurately predicted the prognosis of HCC patients. It was strongly related to the clinical characteristics of HCC patients. Moreover, CENPA/STMN1 might be a key TF-ferrGene regulatory network in ferroptosis of HCC. CENPA and STMN1 were overexpressed in HCC tissues and cells. Additionally, CENPA facilitated STMN1 transcription by binding to STMN1 promoter, thus facilitating the malignant phenotypes and suppressing the ferroptosis of HCC cells. Conclusions: Taken together, CENPA curbs the ferroptosis of HCC cells by upregulating STMN1 transcription, thereby promoting HCC growth.
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BACKGROUND: Previous functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD). Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain's total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients. METHODS: Eighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores. RESULTS: Compared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus. Additionally, ALFF values in left pallidum were positively correlated with Young Mania Rating Scale score in PBD. CONCLUSION: The abnormal resting-state neuronal activities of the basal ganglia, parietal cortex, and occipital cortex may play an important role in the pathophysiology in PBD patients.
