Therapeutic Potential of Natural Compounds in Subarachnoid Haemorrhage.

Subarachnoid hemorrhage (SAH) is a common and fatal cerebrovascular disease with high morbidity, mortality and very poor prognosis worldwide. SAH can induce a complex series of pathophysiological processes, and the main factors affecting its prognosis are early brain injury (EBI) and delayed cerebral ischemia (DCI). The pathophysiological features of EBI mainly include intense neuroinflammation, oxidative stress, neuronal cell death, mitochondrial dysfunction and brain edema, while DCI is characterized by delayed onset ischemic neurological deficits and cerebral vasospasm (CVS). Despite much exploration in people to improve the prognostic outcome of SAH, effective treatment strategies are still lacking. In recent years, numerous studies have shown that natural compounds of plant origin have unique neuro- and vascular protective effects in EBI and DCI after SAH and long-term neurological deficits, which mainly include inhibition of inflammatory response, reduction of oxidative stress, anti-apoptosis, and improvement of blood-brain barrier and cerebral vasospasm. The aim of this paper is to systematically explore the processes of neuroinflammation, oxidative stress, and apoptosis in SAH, and to summarize natural compounds as potential targets for improving the prognosis of SAH and their related mechanisms of action for future therapies.

Impinging Flow Mediates Vascular Endothelial Cell Injury through the PKCα/ERK/PPARγ Pathway in vitro.

INTRODUCTION: This study aimed to elucidate the mechanisms underlying endothelial injury in the context of intracranial aneurysm formation and development, which are associated with vascular endothelial injury caused by hemodynamic abnormalities. Specifically, we focus on the involvement of PKCα, an intracellular signaling transmitter closely linked to vascular diseases, and its role in activating MAPK. Additionally, we investigate the protective effects of PPARγ, a vasculoprotective factor known to attenuate vascular injury by mitigating the inflammatory response in the vessel wall. METHODS: The study employs a modified T-chamber to replicate fluid flow conditions at the artery bifurcation, allowing us to assess wall shear stress effects on human umbilical vein endothelial cells in vitro. Through experimental manipulations involving PKCα knockdown and Ca2+ and MAPK inhibitors, we evaluated the phosphorylation status of PKCα, NF-κB, ERK5, ERK1/2, JNK1/2/3, and P38, as well as the expression levels of PPARγ, NF-κB, and MMP2 via Western blot analysis. The cellular localization of phosphorylated NF-κB was determined using immunofluorescence. RESULTS: Our results showed that impinging flow resulted in the activation of PKCα, followed by the phosphorylation of ERK5, ERK1/2, and JNK1/2/3, leading to a decrease in PPARγ expression, an increase in the expression of NF-κB and MMP2, and the induction of apoptotic injury. Inhibition of PKCα activation or knockdown of PKCα using shRNA leads to a suppression of ERK5, ERK1/2, JNK1/2/3, and P38 phosphorylation, an elevation in PPARγ expression, and a reduction in NF-κB and MMP2 expression, alleviated apoptotic injury. Furthermore, we observe that the regulation of PPARγ, NF-κB, and MMP2 expression is influenced by ERK5 and ERK1/2 phosphorylation, and activation of PPARγ effectively counteracts the elevated expression of NF-κB and MMP2. CONCLUSION: Our findings suggest that the PKCα/ERK/PPARγ pathway plays a crucial role in mediating endothelial injury under conditions of impinging flow, with potential implications for vascular diseases and intracranial aneurysm development.

HMGB1 induced oxidative stress and Inflammation in endothelial cells exposed to Impinging Flow.

BACKGROUND: Oxidative stress and inflammation contribute to many aspects of the pathological processes involved in intracranial aneurysm (IA). However, the underlying mechanism for inducing oxidative stress and inflammation under impinging flow remains unclear. Accumulating evidence has shown that High mobility group box-1 (HMGB1) is associated with oxidative stress-related chronic diseases and inflammatory responses. Therefore, we aimed to investigate whether HMGB1 is involved in oxidative stress and inflammatory responses in endothelial cells (ECs) exposed to impinging flow. METHODS: We used a modified T-chamber to simulate the in vitro situation of human umbilical vein endothelial cells (HUVECs) subjected to impinging flow at the arterial bifurcation in order to analyze the effect of wall shear stress (WSS) on the ECs. To investigate the role of HMGB1 in this process, we transfected ECs with shRNA before conducting impinging flow experiments. Intracellular reactive oxygen species (ROS) were measured by flow cytometry, and malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels were measured to assess oxidative stress. Inflammation was assessed by measuring the mRNA expression levels of IL-1ß, IL-6 and IL-8 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We also examined the cellular localisation of HMGB1 by immunofluorescence. RESULTS: Exposure of HUVECs to WSS can increase the level of oxidative stress and inflammatory response. WSS increased the expression of HMGB1 in ECs and promoted the translocation of HMGB1 from cytosol to cytoplasm. When we knocked down HMGB1, the level of oxidative stress and inflammatory response caused by WSS in ECs decreased, suggesting that HMGB1 can mediate the oxidative stress and inflammatory response in HUVECs exposed to WSS. Conclusions：HMGB1 induced oxidative stress and inflammatory response in ECs exposed to Impinging Flow.

HELLPAR/RRM2 axis related to HMMR as novel prognostic biomarker in gliomas.

BACKGROUND: Gliomas are the most frequent type of central nervous system tumor, accounting for more than 70% of all malignant CNS tumors. Recent research suggests that the hyaluronan-mediated motility receptor (HMMR) could be a novel potential tumor prognostic marker. Furthermore, mounting data has highlighted the important role of ceRNA regulatory networks in a variety of human malignancies. The complexity and behavioural characteristics of HMMR and the ceRNA network in gliomas, on the other hand, remained unknown. METHODS: Transcriptomic expression data were collected from TCGA, GTEx, GEO, and CGGA database.The relationship between clinical variables and HMMR was analyzed with the univariate and multivariate Cox regression. Kaplan-Meier method was used to assess OS. TCGA data are analyzed and processed, and the correlation results obtained were used to perform GO, GSEA, and ssGSEA. Potentially interacting miRNAs and lncRNAs were predicted by miRWalk and StarBase. RESULTS: HMMR was substantially expressed in gliomas tissues compared to normal tissues. Multivariate analysis revealed that high HMMR expression was an independent predictive predictor of OS in TCGA and CGGA. Functional enrichment analysis found that HMMR expression was associated with nuclear division and cell cycle. Base on ssGSEA analysis, The levels of HMMR expression in various types of immune cells differed significantly. Bioinformatics investigation revealed the HEELPAR-hsa-let-7i-5p-RRM2 ceRNA network, which was linked to gliomas prognosis. And through multiple analysis, the good predictive performance of HELLPAR/RRM2 axis for gliomas patients was confirmed. CONCLUSION: This study provides multi-layered and multifaceted evidence for the importance of HMMR and establishes a HMMR-related ceRNA (HEELPAR-hsa-let-7i-5p-RRM2) overexpressed network related to the prognosis of gliomas.

Diagnostic and Predictive Value of Novel Inflammatory Markers of the Severity of Acute Traumatic Spinal Cord Injury: A Retrospective Study.

OBJECTIVE: In order to assess the relationships between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, and systemic immune inflammatory index (SII) and the American Spinal Injury Association Impairment Scale (AIS) grade in patients with acute traumatic spinal cord injury (TSCI). METHODS: We retrospectively investigated 526 patients with acute traumatic spinal cord injury admitted to the First Affiliated Hospital of Nanchang University between January 2012 and December 2021, and for whom routine blood tests were performed within 8 hours of injury. To assess the degree of impairment in TSCI patients using the American Spinal Cord Injury Association Impairment Scale. The patients were divided into 2 groups according to AIS grade as follows: patients with an AIS grade of A-B (severe and critical TSCI, respectively) were distinguished from those with an AIS grade of C-E (minimal, mild, and moderate TSCI, respectively). The association between unfavorable outcomes and each indicator was examined separately through univariate logistic regression analysis. Correlations between variables and AIS grades were analyzed by Spearman's correlation test. The discriminative ability of predictive models was evaluated using the area under the curve. RESULTS: The NLR, PLR, and SII were elevated in patients with spinal cord injury and exceeded the reference values in 95% of cases. The AIS grades were inversely correlated with the NLR, PLR, and SII. In the receiver operating characteristic curve analysis performed to confirm the utility of the NLR, PLR, and SII for predicting the AIS grade, the area under the curve values were 0.710 (95% confidence interval [CI], 0.666-0.755), 0.603 (95% CI, 0.554-0.651) and 0.638 (95% CI, 0.591-0.685), respectively. The optimal cut-off value for the NLR was 0.361 (sensitivity = 0.79, specificity = 0.57). CONCLUSIONS: The analysis of changes in NLR, PLR, and SII as indicators of the novel systemic inflammatory can be an important complement to traditional methods for the assessment of severity and prognosis and the possible selection of patients for close monitoring. And, NLR showed higher diagnostic performance than PLR and SII.

A novel prognostic signature of cuproptosis-related genes and the prognostic value of FDX1 in gliomas.

Background: Gliomas are the most common malignant tumors of the central nervous system, with extremely bad prognoses. Cuproptosis is a novel form of regulated cell death. The impact of cuproptosis-related genes on glioma development has not been reported. Methods: The TCGA, GTEx, and CGGA databases were used to retrieve transcriptomic expression data. We employed Cox's regressions to determine the associations between clinical factors and cuproptosis-related gene expression. Overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were evaluated using the Kaplan-Meier method. We also used the least absolute shrinkage and selection operator (LASSO) regression technique. Results: The expression levels of all 10 CRGs varied considerably between glioma tumors and healthy tissues. In glioma patients, the levels of CDKN2A, FDX1, DLD, DLAT, LIAS, LIPT1, and PDHA1 were significantly associated with the OS, disease-specific survival, and progression-free interval. We used LASSO Cox's regression to create a prognostic model; the risk score was (0.882340) *FDX1 expression + (0.141089) *DLD expression + (-0.333875) *LIAS expression + (0.356469) *LIPT1 expression + (-0.123851) *PDHA1 expression. A high-risk score/signature was associated with poor OS (hazard ratio = 3.50, 95% confidence interval 2, -4.55, log-rank p < 0.001). Cox's regression revealed that the FDX1 level independently predicted prognosis; FDX1 may control immune cell infiltration of the tumor microenvironment. Conclusion: The CRG signature may be prognostic in glioma patients, and the FDX1 level may independently predict glioma prognosis. These data may afford new insights into treatment.

Exploring the molecular mechanism of Sishen Decoction in the treatment of rheumatoid arthritis.

Background: To explore the potential targets and mechanism of action of Sishen Decoction in the treatment of rheumatoid arthritis (RA) using a network pharmacology approach. Methods: Firstly, we analyzed the differentially expressed genes in the Gene Expression Omnibus (GEO) database and constructed a protein-protein interaction (PPI) network using potential core target proteins determined by the STRING platform and Cytoscape software. We also performed gene ontology functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and gene set enrichment analysis (GSEA) on the potential targets, and then used the disease target database to download targets related to RA pathogenesis. The relevant targets were intersected with the action targets of Sishen Decoction to obtain the potential targets considered for the treatment of RA with Sishen Decoction. Results: The GSE55235 and GSE77298 datasets were downloaded from the GEO database for analysis, and 73 genes with abnormally high expression in RA and 26 genes with abnormally low expression in RA were obtained by taking the intersection of highly expressed genes and low expression genes in RA. The results of KEGG and Metascape showed that the differential genes were enriched in inflammation-related signaling pathways such as leukocyte migration, myeloid leukocyte-mediated immunity, and lymphocyte activation, as well as bone activation and bone development, which are closely related to RA. In the exploration of the drug targets of Sishen Decoction for the treatment of RA, it was found that Sishen Decoction may regulate the interleukin (IL)-17) signaling pathway, tumour necrosis factor (TNF) signaling pathway, and chemokine signaling pathway in RA by targeting MMP9 and CXCR4. Conclusions: This study explored the potential targets and signaling pathways of Sishen Decoction in the treatment of RA, which may help to illustrate the mechanisms involved in the action of Sishen Decoction and better understand its anti-RA role in the inhibition of angiogenesis, synovial proliferation, and bone destruction.

Bioinformatics analysis constructs potential ferroptosis-related ceRNA network involved in the formation of intracranial aneurysm.

Background: Intracranial aneurysm (IA) causes more than 80% of nontraumatic subarachnoid hemorrhages (SAHs). The mechanism of ferroptosis involved in IA formation remains unclear. The roles played by competitive endogenous RNA (ceRNA) regulation networks in many diseases are becoming clearer. The goal of this study was to understand more fully the ferroptosis-related ceRNA regulation network in IA. Materials and methods: To identify differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially expressed lncRNAs (DELs) across IA and control samples, the GEO datasets GSE122897 and GSE66239 were downloaded and analyzed with the aid of R. Ferroptosis DEGs were discovered by exploring the DEGs of ferroptosis-related genes of the ferroptosis database. Potentially interacting miRNAs and lncRNAs were predicted using miRWalk and StarBase. Enrichment analysis was also performed. We utilized the STRING database and Cytoscape software to identify protein-protein interactions and networks. DAB-enhanced Prussian blue staining was used to detect iron in IA tissues. Results: Iron deposition was evident in IA tissue. In all, 30 ferroptosis DEGs, 5 key DEMs, and 17 key DELs were screened out for constructing a triple regulatory network. According to expression regulation of DELs, DEMs, and DEGs, a hub triple regulatory network was built. As the functions of lncRNAs are determined by their cellular location, PVT1-hsa-miR-4644-SLC39A14 ceRNA and DUXAP8-hsa-miR-378e/378f-SLC2A3 ceRNA networks were constructed. Conclusion: CeRNA (PVT1-hsa-miR-4644-SLC39A14 and DUXAP8-hsa-miR-378e/378f-SLC2A3) overexpression networks associated with ferroptosis in IA were established.

The Association of Morphological Differences of Middle Cerebral Artery Bifurcation and Aneurysm Formation: A Systematic Review and Meta-Analysis.

OBJECTIVE: We explored the relationships between morphological parameters of middle cerebral artery (MCA) bifurcations based on imaging and the development of middle cerebral aneurysms. Artery bifurcations can form disordered hemodynamics which can promote the development of aneurysms, whereas the hemodynamic environment at the bifurcation tip is highly reliant on the bifurcation's geometry. METHODS: We searched 3 electronic databases for all relevant, publicly available publications as of March 18, 2022. Through the screening of abstracts and full texts, a meta-analysis was performed to compare the daughter-to-daughter angle, the inclination angle (γ), and the parent vessel diameter of MCA bifurcations between patients in MCA aneurysm and non-aneurysm controls. RESULTS: Ten articles describing 1012 patients with MCA aneurysms and 1106 control individuals without aneurysms were included in the analysis. The aneurysm group showed a larger daughter-to-daughter branch angle at MCA bifurcations than the non-aneurysm group (weighted mean difference [WMD] = 42.00; 95% confidence interval [CI], 33.77 to 50.23; P < 0.00001). The daughter-to-daughter angle was also larger in the MCA aneurysm group with than without an aneurysm side branch (WMD = 37.03; 95% CI, 26.57 to 47.50; P < 0.00001), and in the MCA aneurysm group than in the non-aneurysm control group (WMD = 41.87; 95% CI, 29.19 to 54.54; P < 0.00001). The aneurysm group had a larger inclination angle than the control group (WMD = 28.73; 95% CI, 18.78 to 38.69; P < 0.00001). In patients with a MCA aneurysm, the parent vessel of the branch with the MCA aneurysm tended to be smaller in diameter than the contralateral branch without the aneurysm (WMD = -0.12; 95% CI, -0.24 to 0.00; P = 0.05). CONCLUSIONS: A larger daughter-to-daughter angle and larger inclination angle at MCA bifurcations are closely related to MCA bifurcation aneurysms. The parent vessel diameter is negatively related to MCA bifurcation aneurysms.

Increased ASF1B Expression Correlates With Poor Prognosis in Patients With Gliomas.

Background: Several studies have suggested that anti-silencing function 1 B (ASF1B) can serve as a good potential marker for predicting tumor prognosis. But the values of ASF1B in gliomas have not been elucidated and further confirmation is needed. Methods: Transcriptomic and clinical data were downloaded from The Cancer Genome Atlas database (TCGA), genotypic tissue expression (GTEx), and the Chinese Gliomas Genome Atlas database (CGGA). Univariate and multivariate Cox regression analyses were used to investigate the link between clinical variables and ASF1B. Survival analysis was used to assess the association between ASF1B expression and overall survival (OS). The relationship between ASF1B expression and OS was studied using survival analysis. To investigate the probable function and immunological infiltration, researchers used gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA). Results: In glioma tissues, ASF1B expression was considerably higher than in normal tissues. The survival analysis found that increased ASF1B expression was linked with a poor prognosis in glioma patients. ASF1B demonstrated a high diagnostic value in glioma patients, according to a Receiver Operating Characteristic (ROC) analysis. ASF1B was found to be an independent predictive factor for OS in a Cox regression study (HR = 1.573, 95% CI: 1.053-2.350, p = 0.027). GO, KEGG, and GSEA functional enrichment analysis revealed that ASF1B was associated with nuclear division, cell cycle, m-phase, and cell cycle checkpoints. Immuno-infiltration analysis revealed that ASF1B was positively related to Th2 cells, macrophages, and aDC and was negatively related to pDC, TFH, and NK CD56 bright cells. Conclusion: A high level of ASF1B mRNA expression was correlated with a poor prognosis in glioma patients in this study, implying that it could be a reliable prognostic biomarker for glioma patients.

Effects of Cranioplasty on Contralateral Subdural Effusion After Decompressive Craniectomy: A Literature Review.

BACKGROUND: Contralateral subdural effusion (CSE) after decompressive craniectomy (CSEDC) is occasionally observed. Cranioplasty is routinely performed for reconstruction and has recently been associated with improving contralateral subdural effusion. We sought to systematically review all available literature and evaluate the effectiveness of cranioplasty for CSE. METHODS: A PubMed, Web of Science, and Google Scholar search was conducted for preferred reporting items following the guidelines of systematic review and meta-analysis, including studies reporting patients who underwent cranioplasty because of CSEDC. RESULTS: The search yielded 8 articles. A total of 56 patients ranging in age from 21 to 71 years developed CSEDC. Of them, 32 patients underwent cranioplasty. Eighteen cases with symptomatic CSE underwent cranioplasty alone, 2 cases received Ommaya drainage later because of a recurrence of CDC, and 1 case underwent a ventriculoperitoneal shunt because the CSE did not resolve completely and the ventricle was dilated again. The symptoms of 14 cases lessened without recurrence after simultaneous cranioplasty and drainage or a shunt. The total success rate (CSE disappeared without recurrence) was 90.6% for patients who underwent cranioplasty; however, the total incidence of hydrocephalus was 40.1%. CONCLUSIONS: This review suggests that cranioplasty is effective for the treatment of CSEDC, particularly intractable cases, but early cranioplasty may be more effective. In addition, hydrocephalus is fairly common after cranioplasty and requires further treatment.

Impinging Flow Induces Expression of Monocyte Chemoattractant Protein-1 in Endothelial Cells Through Activation of the c-Jun N-terminal Kinase/c-Jun/p38/c-Fos Pathway.

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is an important regulator of the formation and development of intracranial aneurysms. This study explored the molecular mechanisms underlying the induction of MCP-1 and related inflammatory factors in human umbilical vein endothelial cells (HUVECs) under hemodynamic conditions. METHODS: A modified T chamber was used to simulate fluid flow at the bifurcation of the artery and wall shear stress on HUVECs in vitro. Changes in HUVECs were analyzed in response to impinging flow. And HUVECs without impinging flow were used as the control group. Protein expression levels of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, activator protein-1, and MCP-1 were detected by Western blot, and the messenger RNA expression levels of MCP-1, interleukin (IL)-1ß, and IL-6 were determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Under impinging flow, the phosphorylation levels of ERK, JNK, and p38, as well as the protein levels of MCP-1, c-Jun, and c-Fos, increased. The messenger RNA expression of MCP-1, IL-1ß, and IL-6 also increased in HUVECs. Pretreatment of the HUVECs with inhibitors of JNK and p38 significantly attenuated the increased expression of MCP-1, IL-1ß, and IL-6, while ERK inhibitors had no obvious effect. CONCLUSIONS: Under impinging flow, MCP-1 and inflammatory factors are regulated through the JNK/c-Jun/p38/c-Fos pathway and participate in EC inflammation.

Potential Role of the Chemotaxis System in Formation and Progression of Intracranial Aneurysms Through Weighted Gene Co-Expression Network Analysis.

BACKGROUND: Intracranial aneurysm (IA) is the most common and is the main cause of spontaneous subarachnoid hemorrhage (SAH). The underlying molecular mechanisms for preventing IA progression have not been fully identified. Our research aimed to identify the key genes and critical pathways of IA through gene co-expression networks. METHODS: Gene Expression Omnibus (GEO) datasets GSE13353, GSE54083 and GSE75436 were used in the study. The genetic data were analyzed by weighted gene co-expression network analysis (WGCNA). Then the clinically significant modules were identified and the differentially expressed genes (DEGs) with the genes were intersected in these modules. GO (gene ontology) and KEGG (Kyoto Gene and Genomic Encyclopedia) were used for gene enrichment analysis to determine the function or pathway. In addition, the composition of immune cells was analyzed by CIBERSORT algorithm. Finally, the hub genes and key genes were identified by GSE122897. RESULTS: A total of 266 DEGs and two modules with clinical significance were identified. The inflammatory response and immune response were identified by GO and KEGG. CCR5, CCL4, CCL20, and FPR3 were the key genes in the module correlated with IA. The proportions of infiltrating immune cells in IA and normal tissues were different, especially in terms of macrophages and mast cells. CONCLUSION: The chemotactic system has been identified as a key pathway of IA, and interacting macrophages may regulate this pathological process.

The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of rheumatoid arthritis chondrocytes through the ASIC1a/NLRP3 signaling pathway.

Background: Based on the ASIC1a/NLRP3 signaling pathway, we explored the specific molecular mechanism of the pyroptosis of rheumatoid arthritis (RA) chondrocytes by the method of nourishing qi, nourishing yin, and dredging collaterals to provide new ideas for the treatment of this disease. Methods: A total of 50 rats were divided into a normal group, model group, methotrexate group, Yiqi Yangyin Tongluo group, and combined group. Except for the normal control group, the other groups used Freund's complete adjuvant (FCA) to make RA rat model. The arthritis index and ankle joint swelling of rats in each group were recorded. HE staining and ELISA were used to assess the pathology of the ankle joint of each group of rats and the content of IL-1ß and IL-18 in rat serum. Furthermore, immunofluorescence and qPCR methods were used to detect the protein and mRNA expression levels of NLRP3, caspase 1, ACS, and ASIC1a in the cartilage tissue of each group of rats. Results: Compared with the normal group, the right hind foot joint of the model group was significantly swollen, the levels of IL-18 and IL-1ß in the serum of rats increased significantly, and the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes also increased significantly. Compared with the model group, the degree of ankle joint swelling and IL-18 and IL-1ß content in rat serum in each medication group was significantly reduced, and the combined group showed the greatest reduction compared with the other groups. After 8 weeks of treatment, compared with the model group, the mRNA and protein levels of NLRP3, caspase 1, ACS, and ASIC1a in the chondrocytes of each medication group were down-regulated. HE staining found that there were large numbers of infiltrating inflammatory cells and pannus in the joint tissue of the model group, while only a small amount of inflammatory cell infiltration and pannus was seen in the joint tissue of the rats in each treatment group. Conclusions: The method of Yiqi Yangyin Tongluo can attenuate the pyroptosis of RA chondrocytes through the ASIC1a/NLRP3 signaling pathway.

Analysis of differentially expressed circular RNAs in endothelial cells under impinging flow.

BACKGROUND: Circular RNAs (circRNAs) are a special type of non-coding RNA. To elucidate the relationship between hemodynamics and the function of circRNAs in endothelial cells (ECs), a modified T chamber system was designed and produced for the present experiment. This T chamber system can be used to simulate the hemodynamic environment at the bifurcation of the arteries. METHODS: Normal ECs cultured on glass slides were placed in the T chamber, the cell layer was impacted at a flow rate of 500 mL/min, and high-throughput microarrays were used to analyze the expression profiles of circRNAs in ECs. The differential expressions of circRNAs in the ECs treated with impinging flow were compared to those in ECs in conventional culture conditions. The characteristics of the differentially expressed circRNAs were analyzed with bioinformatics and quantitative reverse transcription polymerase chain reaction analyses were conducted to verify results. RESULTS: Compared to normal samples, there were changes in the expressions of many circRNAs. A total of 974 circRNAs were differentially expressed, and of these, 378 were upregulated and 596 were downregulated (fold change [FC] ≥ 2 and P < 0.05), which suggests that these circRNAs were altered under hemodynamic conditions. CONCLUSIONS: We present the differential expression profiles of circRNAs in ECs after the application of impinging flow; our results indicate that these differentially expressed circRNAs may be involved in inflammatory responses and damage in ECs. The present findings provide valuable information on cRNA profiles as well as clues for future studies that will investigate the roles that circRNAs play in ECs after inflammatory injury.

Clinical nomogram for predicting the survival of patients with cerebral anaplastic gliomas.

The present study aimed to develop an effective nomogram for predicting the overall survival (OS) of patients with cerebral anaplastic glioma (AG).This study included 1939 patients diagnosed with AG between 1973 and 2013 who were identified using the Surveillance, Epidemiology, and End Results database. A multivariate Cox regression analysis revealed that age, histology, tumor site, marital status, radiotherapy, and surgery were independent prognostic factors and, thus, these factors were selected to build a clinical nomogram. Harrell's concordance index (C-index) and a calibration curve were formulated to evaluate the discrimination and calibration of the nomogram using bootstrapping.A nomogram was developed to predict 5- and 9-year OS rates based on 6 independent prognostic factors identified in the training set: age, tumor site, marital status, histology, radiotherapy, and surgery (P < .05). The Harrell's concordance index values of the training and validation sets were 0.776 (0.759-0.793) and 0.766 (0.739-0.792), respectively. The calibration curve exhibited good consistency with the actual observation curve in both sets.Although the prognostic value of the World Health Organization (WHO) classification has been validated, we developed a novel nomogram based on readily available clinical variables in terms of demographic data, therapeutic modalities, and tumor characteristics to predict the survival of AG patients. When used in combination with the WHO classification system, this clinical nomogram can aid clinicians in making individualized predictions of AG patient survival and improving treatment strategies.

The Role of Circular RNAs in Brain Injury.

Circular RNAs are an increasingly important topic in non-coding RNA biology, drawing considerable attention in recent years. Accumulating evidence suggests a critical role for circular RNAs in both early and latent stages of disease pathogenesis. Circular RNAs are abundantly expressed in brain tissue, with significant implications for neural development and disease progression. Disruption of these processes, including those seen in response to brain injury, can have serious consequences such as hemiplegia, aphasia, coma, and death. In this review, we describe the role of circular RNAs in the context of brain injury and explore the potential connection between circular RNAs, brain hypoxic ischemic injury, ischemia-reperfusion injury, and traumatic injury.

Fluid Shear Stress Induces Endothelial Cell Injury via Protein Kinase C Alpha-Mediated Repression of p120-Catenin and Vascular Endothelial Cadherin In Vitro.

OBJECTIVE: The present study aimed to characterize the mechanism of fluid shear stress (FSS)-induced endothelial cell (EC) injury via protein kinase C alpha (PKCα)-mediated vascular endothelial cadherin (VE-cadherin) and p120-catenin (p120ctn) expression. METHODS: We designed a T chamber system that produced stable FSS on ECs in vitro. Human umbilical vein endothelial cells (HUVECs) in which PKCα was knocked down and normal HUVECs were cultured on the coverslips. FSS was impinged on these 2 types of ECs for 0 hours and 6 hours. The morphology and density of HUVECs were evaluated, and expression levels of phosphorylated PKCα, p120-catenin (p120ctn), VE-cadherin, phosphorylated p120ctn at S879 (p-S879p120ctn), and nuclear factor kappa B (NF-κB) were analyzed by Western blot. RESULTS: HUVECs exposed to FSS were characterized by a polygonal shape and decreased cell density. The phosphorylated PKCα level was increased under FSS at 6 hours (P < 0.05). In normal HUVECs during FSS, p120ctn and VE-cadherin were decreased, whereas p-S879p120ctn and NF-κB were increased, at 6 hours (P < 0.05). In HUVECs after PKCα knockdown, p120ctn and VE-cadherin were not significantly changed (P > 0.05), p-S879p120ctn was undetectable, but NF-κB was decreased (P < 0.05) at 6 hours. CONCLUSIONS: The possible mechanism of FSS-induced EC injury may be as follows: 1) PKCα induces low expression of p120ctn, which leads to activation of NF-κB and degradation of VE-cadherin; 2) PKCα-mediated phosphorylation of p120ctn at S879 disrupts p120ctn binding to VE-cadherin.

A prognostic nomogram for distal bile duct cancer from Surveillance, Epidemiology, and End Results (SEER) database based on the STROBE compliant.

In this study, we aimed to develop a reliable nomogram to estimate individualized prognosis for patients with distal bile duct cancer (DBDC) and compare the predictive value with the American Joint Committee on Cancer staging system.Data of 1110 patients diagnosed with DBDC were recruited from the Surveillance, Epidemiology, and End Results database between 1973 and 2015. All patients were randomly divided into the training (n = 777) and validation (n = 333) cohorts, respectively. Multivariate Cox regression was performed to identify the independent risk factors. The Akaike information criterion was used to select covariates for constructing a nomogram. The predictive ability of the nomogram was assessed by concordance index (C-index) and area under receiver operating characteristic curve (AUROC) compared to tumor-node-metastasis (TNM) staging system.A nomogram integrating 8 risk factors was developed with a higher C-index than that of the TNM staging system (training data set, 0.70 vs 0.61; validation data set, 0.71 vs 0.57). The AUROCs of the nomogram for 1-year and 3-year overall survival (OS) predication were 0.76 and 0.78 in the training cohort, 0.78 and 0.77 in the validation cohort. However, AUROCs of the TNM stage for predicting 1-year and 3-year OS were all below 0.60. Calibration curves showed the optimal agreement in predicating OS between nomogram and actual observation. In addition, this nomogram can effectively distinguish the OS between low and high-risk groups divided by the median score (P < .01).Present study was the first one to construct a prognostic nomogram of DBDC patients, which has the potential to provide individual prediction of OS.

A Nomogram for Predicting Individual Prognosis of Patients with Low-Grade Glioma.

OBJECTIVE: The present study aimed to develop and evaluate a nomogram for predicting the overall survival (OS) of patients with low-grade glioma (LGG). METHODS: Patients with LGG diagnosed from 1973 to 2013 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. A total of 3732 patients were randomly divided into a training set (n = 2612) and a validation set (n = 1120). Univariate and multivariate Cox regression analyses of the clinical variables were performed to screen for significant prognostic factors. Next, a nomogram that included significant prognostic variables was formulated to predict for LGG. Harrell's concordance index (C-index) and calibration plots were formulated to evaluate the reliability and accuracy of the nomogram using bootstrapping according to the internal (training set) and external (validation set) validity. RESULTS: A nomogram was developed to predict the 5- and 9-year OS rates using 7 variables in the training set: age, tumor site, sex, marital status, histological type, tumor size, and surgery (P < 0.05). The C-index for internal validation, which the nomogram used to predict OS according to the training set, was 0.777 (range, 0.763-0.791), and the C-index for external validation (validation set) was 0.776 (range, 0.754-0.797). The results of the calibration plots showed that the actual observation and prediction values obtained by the nomogram had good consistency between the 2 sets. CONCLUSIONS: We have developed a ready-to-use nomogram model that includes clinical characteristics to predict OS. The nomogram might provide consultation and risk assessments for subsequent treatment of patients with LGG.