Pathogenic mechanism of Vibrio vulnificus infection.

Vibrio vulnificus is a fatal, opportunistic human pathogen transmitted through the consumption of raw/undercooked seafood or direct contact. V. vulnificus infection progresses rapidly and has severe consequences; some cases may require amputation or result in death. Growing evidence suggests that V. vulnificus virulence factors and regulators play a large role in disease progression, involving host resistance, cellular damage, iron acquisition, virulence regulation and host immune responses. Its disease mechanism remains largely undefined. Further evaluation of pathogenic mechanisms is important for selecting appropriate measures to prevent and treat V. vulnificus infection. In this review, the possible pathogenesis of V. vulnificus infection is described to provide a reference for treatment and prevention.

Maternally Expressed Gene 3 Negatively Regulated Decorin to Supresse Angiogenesis, Proliferation and Migration of Endothelial Cells.

BACKGROUND: Angiogenesis of tumor cells is highly associated with tumorsecreted factors and matrix proteins. However, the underlying mechanism of tumorsecreted factors and matrix proteins during angiogenesis is rarely discussed. OBJECTIVES: This study investigated the relationship between the maternally expressed gene 3 (MEG3), a tumor-secreted growth factor, and Decorin, a tumor-secreted matrix protein, and evaluated their derivate roles in human endothelial cell development. METHODS: Human endothelial cells were transiently transfected with a plasmid expressing antisense of Decorin mRNA (shDecorin) and silencing mRNA of MEG3 (siMEG3) or MEG3 over-expressive vectors. A series of qPCR and Western blot analysis was applied to characterize the expressions of MEG3 and Decorin in all transfected cells. Moreover, scratch, Transwell, and Matrigel neovascularization assays were performed to examine three key processes of endothelial cells' angiogenesis, including tubulogenesis, proliferation, and migratory levels. In addition, the cell viability was evaluated at each step via the MTT test. RESULTS: The overexpression of MEG3 inhibited angiogenesis and migration of endothelial cells by preventing the expression of Decorin. At the same time, the inhibition of MEG3 via siRNA resulted in an increased expression of Decorin, enhanced tube formation levels, and promoted endothelial cell proliferation and migration. Furthermore, Decorin's knockdown suppressed the angiogenesis and migration of endothelial cells without affecting the expression of MEG3. Importantly, the stimulation of HUVEC cells with exogenous Decorin protein alleviated most phenotypes induced by the upregulation of MEG3. CONCLUSION: Our study demonstrated the anti-growth effects of MEG3 on vasculogenesis and migration of endothelial cells. Thus, by blocking the expression of Decorin in HUVECs, the overexpression of MEG3 repressed their development and might potentially alleviate the ischemic stroke.

The Diagnostic Value of Whole Blood lncRNA NR_120420 for Acute Ischemic Stroke.

OBJECTIVE: Current clinical practice based on CT or multimodal images to diagnose ischemic stroke always led to substantial treatment delay. We perform this study to explore possible circulating lncRNA biomarker to help promptly diagnose the disease. METHODS: We used microarray to identify the differentially expressed lncRNAs in the peripheral whole blood between AIS patients and controls and verified the results by quantitative polymerase chain reaction (qPCR). Multivariate logistic regressions were performed to determinate the lncRNAs independently associated with AIS occurrence. The ROC curve was used to detect the diagnostic accuracy of candidate lncRNAs in AIS and AIS subtypes, which was classified according to the Oxford Community Stroke Project (OCSP) criteria. RESULTS: The microarray analysis screened out 5686 differentially expressed lncRNAs. Among the nine selected lncRNAs verified by qPCR, NR_120420 (OR 1.29, 95% CI 1.02-1.65, P = 0.037) was found independently associated with AIS after balancing patient baseline characteristics. The receiver operating characteristic (ROC) analysis concerning NR_120420 in total anterior circulation infarction subgroup showed that the area under the curve was 0.86 (95% CI: 0.73-0.99, P = 0.003), and at the optimal cutoff point of 1.93, the sensitivity and specificity reached 85.7% and 84.6%, respectively. CONCLUSION: Our study indicated that NR_120420 could predict the total anterior circulation infarction with high sensitivity and specificity and could be potentially used as a biomarker for total anterior circulation infarction in AIS patients.

Comparison of self-expandable stents and balloon-mounted stents in the treatment of symptomatic intracranial vertebral artery atherosclerotic stenosis.

OBJECTIVE: To compare the safety and efficacy of self-expandable stents (SES) and balloon-mounted stents (BMS) in the treatment of severe symptomatic intracranial vertebral artery atherosclerotic stenosis (SIVAAS). METHODS: The clinical and imaging data of 76 consecutive cases who were stented for SIVAAS in our centers in ten years were reviewed retrospectively. The cases were divided into SES group and BMS group as per the type of stents. Conventional risk factors of atherosclerosis, the relationship between stenosis and the origin of posterior inferior cerebellar artery (PICA), whether the stenosis was located at the dural-entry zone of the vertebral artery (VA), the interventional access, periprocedural complications, and clinical and imaging follow-up results were analyzed statistically. RESULTS: 77 stenotic lesions in 76 cases were included. Totally 51 SES and 26 BMS were implanted successfully. There was no significant difference in periprocedural complications (1 vs. 2, P = 0.544), incidence of restenosis (13.2% vs. 14.3%, P = 0.628) and long-term death or stroke (4 vs. 7, P = 0.33) between the two groups. The degree of residual stenosis in SES group was higher than in BMS group (10 (0%-40%) vs. 0 (0%-15%); P = 0). More BMS were selected in lesions located at the dural-entry zone of VA (45.1% vs. 73.1%, P = 0.02). There were more BMS implanted when lesions located proximal to origin of PICA (SES vs. BMS = 23.5% vs. 57.7%, P = 0.003) or when lesions with straighter access (SES vs. BMS = 29.4% vs. 69.2%, P = 0.001). More SES implanted when lesions located distal to PICA (SES vs. BMS = 43.1% vs. 15.4%, P = 0.015) or when lesions with moderate tortuous access (SES vs. BMS = 60.8% vs. 23.1%, P = 0.002). For stenotic lesions with moderate tortuous interventional access, SES group cases had longer survival time without stroke or death (P = 0.008). CONCLUSION: Both SES and BMS showed high safety and efficacy for the treatment of SIVAAS. SES was more recommended for the stenotic lesions with tortuous interventional access. BMS was more recommended for the lesions located at the dural-entry zone of VA or proximal to PICA origin.

lncRNA NR_120420 promotes SH-SY5Y cells apoptosis by regulating NF-κB after oxygen and glucose deprivation.

Stroke has serious implications on patients and a huge impact on society. The current treatment regimens with drug for acute cerebral infarction are unsatisfactory. Here, we explore whether the two long non-coding RNA (lncRNA) candidates from preliminary research regulate apoptosis after cerebral infarction, and evaluate the underlying mechanism of action. Bioinformatics analysis of the lncRNA microarray in the preliminary research of our group was performed. Changes in the expression of candidate lncRNAs in SH-SY5Y cells were detected by quantitative polymerase chain reaction (qPCR) after treatment with seven different oxygen and glucose deprivation (OGD) methods. The changes were detected after transfection of cells with six small-interfering RNAs (siRNAs). Cell models were established by OGD after transfection with siRNAs. Cell viability was evaluated with the cell counting kit 8 (CCK8) assay, while TUNEL staining and flow cytometry analysis were performed to determine apoptosis. Changes in the expression and phosphorylation of three proteins were detected by western blotting after the knockdown of NR_120420. Changes in the expression and phosphorylation of P65 protein were detected by western blotting after this cell model was treated with PDTC. Cells were transfected with siNR_120420 and treated with and without PDTC, followed by analysis of cell viability and apoptosis. Bioinformatics analysis revealed that the differentially expressed lncRNAs after acute cerebral infarction were mainly involved in nuclear factor kappa B (NF-κB) and apoptosis. Expression of the two lncRNA candidates in SH-SY5Y cells was the maximum after incubation under the OGD condition for 8 h. The knockdown efficiency was more than 60% for four of the six siRNAs, and knockdown of NR_120420 increased the cell viability and decreased the percentage of TUNEL-positive cells and apoptotic cells. Knockdown of lnc-GCH1-2:3 resulted in none of these effects. Phosphorylation of NF-κB (P65) decreased significantly after the knockdown of NR_120420. Expression and phosphorylation of P65 was significantly reduced after it was treated with PDTC. The inhibitor of NF-κB (PDTC) could abolish the effect of NR_120420 on the regulation of apoptosis in this cell model. Both NR_120420 and lnc-GCH1-2:3 had significant changes in this cell model. Knockdown of NR_120420 inhibited the apoptosis of cells, while NR_120420 knockdown inhibited apoptosis after cerebral infarction by downregulating the phosphorylation of a subunit of NF-κB (P65). This study may provide new idea for improving drug treatment of acute cerebral infarction.

Plasma MicroRNA-16 Is a Biomarker for Diagnosis, Stratification, and Prognosis of Hyperacute Cerebral Infarction.

Indices for the diagnosis of hyperacute cerebral infarction (HACI) and the prediction of prognosis are essential for timely and appropriate management. MicroRNAs (miRNAs) that regulate gene expression following stroke have potential use as prognostic markers of HACI. Here, we explored whether concentrations of circulating miRNAs correlate with clinical outcomes and thus form a system of stroke stratification. Plasma samples from patients with HACI (n = 7) and age-matched healthy volunteers (HVT, n = 4) were screened by microarray to find differentially expressed miRNAs, some of which were further verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (HACI:HVT = 33:23). The target genes of the miRNAs with verified differential expression were investigated by GO and KEEG analyses. Using the TOAST (OCSP) criteria and the 3-month modified Rankin Score (mRS), relationships among the expression patterns of specific miRNAs, stroke stratification, and clinical prognosis were determined. The microarray analysis revealed 12 differentially expressed miRNAs. Among seven selected miRNAs verified with qRT-PCR, miR-16 expression in the HACI group was the most significantly different from the HVT group (P < 0.01). Bioinformatics analysis showed that the potential target genes of miR-16 were mainly involved in programmed cell death and the p53 signaling pathways. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of miR-16 was 0.775 (sensitivity 69.7% and specificity 87%) and 0.952 (sensitivity 100% and specificity 91.3%) in overall patients and patients with large artery atherosclerosis (LAAS), respectively. Elevated miR-16 expression was associated with the stroke subtype of LAAS, total anterior circulation infarction, partial anterior circulation infarction, and poor prognosis (P < 0.05). A diagnostic method based on rapid measurement of plasma miR-16 has the potential to identify hyperacute cerebral infarction with LAAS with high sensitivity and specificity, which would inform and improve early treatment decisions and disease management.

A novel proximal end stenting technique for assisting embolization of a complex true posterior communicating aneurysm.

Stent-assisted coiling has been widely used for endovascular treatment in recent years with satisfying clinical outcomes. The implantation of a stent using the regular approach, however, may not be safe or effective for certain aneurysms with complex structures. In this study, we report a novel stenting technique utilizing the proximal end of the stent for assisting embolization of a wide-neck irregular true posterior communicating aneurysm. This new method is a potential treatment strategy for wide-neck aneurysms located at the origin of a tortuous and thin vessel.