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Glioblastoma (GBM) is a malignant intracranial tumour with the highest proportion and lethality. It is characterized by invasiveness and heterogeneity. However, the currently available therapies are not curative. As an essential environmental cue that maintains glioma stem cells, hypoxia is considered the cause of tumour resistance to chemotherapy and radiation. Growing evidence shows that immunotherapy focusing on the tumour microenvironment is an effective treatment for GBM; however, the current clinicopathological features cannot predict the response to immunotherapy and provide accurate guidance for immunotherapy. Based on the ESTIMATE algorithm, GBM cases of The Cancer Genome Atlas (TCGA) data set were classified into high‐ and low‐immune/stromal score groups, and a four‐gene tumour environment‐related model was constructed. This model exhibited good efficiency at forecasting short‐ and long‐term prognosis and could also act as an independent prognostic biomarker. Additionally, this model and four of its genes (CLECL5A, SERPING1, CHI3L1 and C1R) were found to be associated with immune cell infiltration, and further study demonstrated that these four genes might drive the hypoxic phenotype of perinecrotic GBM, which affects hypoxia‐induced glioma stemness. Therefore, these might be important candidates for immunotherapy of GBM and deserve further exploration.  相似文献   
103.
Intracoronary application of nicorandil can effectively reduce the myocardial no‐reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro‐inflammatory cytokines was significantly increased, while the anti‐inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.  相似文献   
104.
Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Few studies have focused on the changes of NK, T‐ and B‐cell subsets, inflammatory cytokines and virus‐specific antibodies in patients with moderate COVID‐19. A total of 11 RT‐PCR‐confirmed convalescent patients with COVID‐19 and 11 patients with non‐SARS‐CoV‐2 pneumonia (control patients) were enrolled in this study. NK, CD8+ T, CD4+ T, Tfh‐like and B‐cell subsets were analysed using flow cytometry. Cytokines and SARS‐CoV‐2‐specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID‐19 than in control patients (P = 0.017). Effector memory CD8+ T‐cell counts significantly increased in patients with COVID‐19 during a convalescent period of 1 week (P = 0.041). TIM‐3+ Tfh‐like cell and CD226+ Tfh‐like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS+ Tfh‐like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS‐CoV‐2. The increase in effector memory CD8+ T‐cell counts, the up‐regulation of inhibitory molecules and the down‐regulation of active molecules on CD4+ T cells and Tfh‐like cells in patients with COVID‐19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID‐19.  相似文献   
105.
Brassica rapa L., also called NIUMA, is used empirically in Tibetan medicine for its antioxidant, anti‐inflammatory and antiradiation activities. This study explored the hepatoprotective effects of B. rapa polysaccharides (BRPs) on acute liver injury induced by carbon tetrachloride (CCl4) in mice and the underlying mechanisms. Mice were treated with CCl4 after the oral administration of BRPs (55, 110 and 220 mg/kg) or bifendate (100 mg/kg) for 7 days. Blood and liver samples of mice were collected for analysis after 24 h. The ALP, ALT and AST levels and the biological activities of SOD, MDA and GSH?Px were measured. Histopathological changes in the liver were determined through hematoxylin and eosin staining. Moreover, TNF‐α, IL‐1β and IL‐6 expression levels were detected by commercial reagent kits. Finally, Western blot analysis was used to check the relative expression levels of caspase‐3, p‐JAK2 and p‐STAT3. The BRP pre‐treatment significantly decreased the enzymatic activities of ALT, ALP and AST in the serum, markedly increased the activities of SOD and GSH?Px in the liver and reduced the MDA concentration in the liver. BRPs alleviated hepatocyte injury and markedly inhibited the expression of TNF‐α, IL‐1β and IL‐6, also downregulating the CCl4‐induced hepatic tissue expression of caspase‐3. Furthermore, BRPs inhibited the JAK2/STAT3 signaling pathway in a dose‐dependent manner in the liver. This study demonstrated that BRPs exert hepatoprotective effect against the CCl4‐induced liver injury via modulating the apoptotic and inflammatory responses and downregulating the JAK2/STAT3 signaling pathway. Therefore, B. rapa could be considered a hepatoprotective medicine.  相似文献   
106.
LncRNA and miRNA are key molecules in mechanism of competing endogenous RNAs(ceRNA), and their interactions have been discovered with important roles in gene regulation. As supplementary to the identification of lncRNA‐miRNA interactions from CLIP‐seq experiments, in silico prediction can select the most potential candidates for experimental validation. Although developing computational tool for predicting lncRNA‐miRNA interaction is of great importance for deciphering the ceRNA mechanism, little effort has been made towards this direction. In this paper, we propose an approach based on linear neighbour representation to predict lncRNA‐miRNA interactions (LNRLMI). Specifically, we first constructed a bipartite network by combining the known interaction network and similarities based on expression profiles of lncRNAs and miRNAs. Based on such a data integration, linear neighbour representation method was introduced to construct a prediction model. To evaluate the prediction performance of the proposed model, k‐fold cross validations were implemented. As a result, LNRLMI yielded the average AUCs of 0.8475 ± 0.0032, 0.8960 ± 0.0015 and 0.9069 ± 0.0014 on 2‐fold, 5‐fold and 10‐fold cross validation, respectively. A series of comparison experiments with other methods were also conducted, and the results showed that our method was feasible and effective to predict lncRNA‐miRNA interactions via a combination of different types of useful side information. It is anticipated that LNRLMI could be a useful tool for predicting non‐coding RNA regulation network that lncRNA and miRNA are involved in.  相似文献   
107.
Abnormal mitochondrial fission and mitophagy participate in the pathogenesis of many cardiovascular diseases. Baicalein is a key active component in the roots of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. It has been reported that baicalein can resist cardiotoxicity induced by several stress, but the mechanisms of baicalein operate in the protection of cardiomyocytes need to be researched further. Here we report that baicalein can promote cell survival under oxidative stress by up‐regulating the expression level of MARCH5 in cardiomyocytes. Pre‐treatment cells or mice with baicalein can stabilize the expression of MARCH5, which plays a crucial role in the regulation of mitochondrial network and mitophagy. Overexpressed MARCH5 is able to against H2O2 and ischaemia/reperfusion (I/R) stress by suppressing mitochondrial fission and enhancing mitophagy, and then attenuate cells apoptosis. Altogether, our present study investigated that baicalein exerts a protective effect through regulating KLF4‐MARCH5‐Drp1 pathway, our research also provided a novel theoretical basis for the clinical application of baicalein.  相似文献   
108.
Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are required to limit immune‐induced pathology and to maintain homeostasis during the early‐phase of sepsis. This study aimed to investigate the role of interleukin (IL)‐38, a newly described member of the IL‐1 cytokine family, in mediated immune response of CD4+CD25+ Tregs in sepsis. Here, we provide evidence that expressions of IL‐38 and its receptor were detected in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up‐regulated the expression of IL‐38. Treatment with rmIL‐38 dramatically enhanced the immunosuppressive activity of CD4+CD25+ Tregs after LPS stimulation and in septic mice induced by CLP, resulting in amplification of helper T cell (Th) 2 response and reduction in the proliferation of effector T cells. These effects were robustly abrogated when anti–IL‐38 antibody was administered. Administration of rmIL‐38 improved the survival rate of CLP mice. In addition, CD4+CD25+ Tregs depletion before the onset of sepsis obviously abolished IL‐38–mediated protective response. These findings suggest that IL‐38 enhances the immunosuppressive activity of CD4+CD25+ Tregs, which might contribute to the improvement of host immune function and prognosis in the setting of sepsis.  相似文献   
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