Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH), we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.
Abnormal expression of phosphatidylethanolamine-binding protein 4 (PEBP4) has been found in various types of malignancies. However, the PEBP4 expression in human gliomas is still unclear. In this study, we aim to compare the expression of PEBP4 in tumor samples derived from 58 patients with different grades of gliomas with that in 5 non-neoplastic brain samples and to investigate the clinical significance of PEBP4 expression in gliomas. The mRNA and protein expressions of PEBP4 were measured by real-time quantitative polymerase chain reaction and western blot, respectively. The intracellular expressions of PEBP4 in samples were examined by immunohistochemistry. The association between PEBP4 expression and the clinicopathologic characteristics of gliomas patients were analyzed. Our results demonstrated that the mRNA and protein levels of PEBP4 were upregulated in gliomas tissues, especially in high-grade (World Health Organization Grades III and IV) gliomas, when compared to normal control (p < 0.01). Immunohistochemical analysis indicated that PEBP4 was highly expressed in 82.4% (28/34) of high-grade gliomas, when compared to 41.7% (10/24) of high expression in low-grade gliomas and 20.0% (1/5) in non-neoplastic brain samples (p = 0.001). Multivariate Cox regression analysis revealed that increased PEBP4 expression was an independent prognostic factor for gliomas. Patients with low level of PEBP4 had longer survival time compared to those with high PEBP4 expression (p = 0.003). These data indicate a clinical significance of PEBP4 for predicting the tumor grade and the prognosis in patients with gliomas.
Nicardipine is a dihydropyridine-type Ca(2+) channel blocker with a powerful antihypertensive activity and a unique cerebrovascular profile. Recent studies have examined nicardipine for the treatment of patients with aneurysmal subarachnoid haemorrhage (SAH), but have shown inconsistent results. In the current study, a meta-analysis was performed to assess the clinical effectiveness of nicardipine in the prevention of cerebral vasospasm in patients who had suffered from aneurysmal SAH. Medline, EMBASE, and PubMed databases were searched for the controlled trials evaluating nicardipine for treating SAH after a ruptured aneurysm, without language restrictions. Moreover, a manual search of the bibliographies of relevant articles was also conducted. Two researchers of the present study independently performed the literature search and the data extraction. The meta-analyses were performed using the software RevMan 4.2.10 (provided by the Cochrane Collaboration, Oxford, UK). Five published manuscripts involving 1,154 patients were included in this meta-analysis. Nicardipine infusion reduced the risk of poor outcome (death, vegetative state, or dependency) and mortality, with an odds ratio (OR) of 0.58 [95 % confidence interval (CI) 0.37-0.90] and 0.45 (95 % CI 0.15-1.29), respectively. This meta-analysis suggests that nicardipine therapy reduces the likelihood of poor outcome and mortality in patients after aneurysmal SAH.
Phosphatidylethanolamine (PE)‐binding protein 4 (PEBP4) is an antiapoptotic protein that is aberrantly expressed in various malignancies. We previously demonstrated that PEBP4 expression is dramatically induced in human gliomas and positively correlated with tumor grade and patient survival. However, the function of PEBP4 in human glioma development and underlying mechanisms remain largely unknown. By stable lentiviral vector‐mediated silencing of PEBP4, we examined the effects of PEBP4 knockdown on the growth, apoptosis, and invasion of U251 and U373 human glioma cell lines using MTT, Transwell, colony formation, and flow cytometric assays. We examined the in vivo role of PEBP4 in tumor growth by inoculation of BALB/c nu/nu male mice with PEBP4‐deficient U251 and U373 cells. The expression of cell cycle‐ and apoptosis‐related proteins was analyzed by Western blotting and immunostaining. Knockdown of PEBP4 significantly reduced the proliferation and invasion of human glioma cells while inducing cell apoptosis by altering the expression of cell cycle‐ and apoptosis‐related proteins. Mechanistically, PEBP4 knockdown led to activation of the extracellular signal‐regulated kinases 1/2 (ERK1/2) pathway, an effect that could be reversed by U0126, a selective inhibitor of MEK1/2 (upstream of ERK1/2), suggesting involvement of ERK1/2 signaling in the regulation of glioma development and progression by PEBP4. We identified PEBP4 as a novel regulator mediating human glioma cell proliferation, invasion, and apoptosis as well as tumor formation and growth. Therefore, PEBP4 may be a potential therapeutic target in human glioma treatment.
Coronavirus disease 2019 (COVID-19) is a highly infectious epidemic disease that has seriously affected human health worldwide. To date, however, there is still no definitive drug for the treatment of COVID-19. Cell-based therapies could represent a new breakthrough. Over the past several decades, mesenchymal stromal cells (MSCs) have proven to be ideal candidates for the treatment of many viral infectious diseases due to their immunomodulatory and tissue repair or regeneration promoting properties, and several relevant clinical trials for the treatment of COVID-19 have been registered internationally. Herein, we systematically summarize the clinical efficacy of MSCs in the treatment of COVID-19 based on published results, including mortality, time to symptom improvement, computed tomography (CT) imaging, cytokines, and safety, while elaborating on the possible mechanisms underpinning the effects of MSCs, to provide a reference for subsequent studies.
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