Bioinformatics Analysis of a Functional ANGPT1 Variant That Interferes with miR-607 and Its Association with Susceptibility and Outcome of Ischemic Stroke in a Han Population.

PURPOSE: Ischemic stroke (IS) is a major cause of disability and death. We used bioinformatics approaches to investigate a functional ANGPT1 variant that interferes with miR-607 and explored its association with IS. MATERIALS AND METHODS: An IS expression microarray (GSE16561) was downloaded from the GEO and used to identify differentially expressed genes (DEGs) and functional enrichment pathways. Analyses showed that ANGPT1 participated in six key pathways and was susceptible to a key functional polymorphism rs2507799. We genotyped 567 IS patients and 500 controls for ANGPT1 rs2507799. Luciferase assays were also conducted to investigate the binding between miR-607 and ANGPT1 rs2507799. RESULTS: In total, we identified 458 DEGs between IS patients and healthy controls in the GSE16561 dataset. GO functional enrichment analysis showed that these DEGs were mainly enriched in cell-substrate junctions, the regulation of peptide secretion, and the regulation of cytokine secretion involved in immune response. ANGPT1 rs2507799 T-carriers had a significantly higher risk of IS (Dominant model: OR = 1.48, 95% CI = 1.01-2.17, P = 0.044). IS patients harboring the TC/TT genotype experienced significantly more severe injuries in terms of neurological function (Dominant model: OR = 2.06, 95% CI = 1.28-3.31, P = 0.003). Analysis also showed that IS patients harboring the TC/TT genotype had a significantly worse outcome (Dominant model: OR = 2.22, 95% CI = 1.35-3.67, P = 0.002). Luciferase assays indicated that miR-607 could affect luciferase activity by binding to the ANGPT1 mutant type. CONCLUSION: In this study, we used bioinformatical methods to investigate a key IS-related gene ANGPT1 and its functional polymorphism rs2507799. rs2507799 was found to be associated with a significantly increased risk for IS, a significantly more severe initial stroke severity, and a worse outcome. These results may help to improve the future management of ischemic stroke.

Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson's Disease.

Parkinson's disease (PD) is a chronic and progressive degenerative disease of the central nervous system. Degenerative neuropathy can occur in patients with PD even before typical clinical symptoms appear in the preclinical stage. Therefore, if the early diagnosis of degenerative diseases can be timely and the correlation with the disease progression can be explored, the disease progression will be slowed down and the quality of life of patients will be improved. In this study, the circRNA microarray was employed to screen the dysregulated circRNA in plasma samples of PD. Four circRNAs (circ_0085869, circ_0004381, circ_0017204, and circ_0090668) were obtained with increased levels in PD patients by cross comparison and preliminary verification in PD comparing with healthy controls. Further validation found the circRNA panel was consistent with the training set. The ROC curve also revealed a high diagnostic ability of circ_0004381 and circ_0017204 in predicting the early stage of PD from healthy controls. circ_0085869, circ_0004381, circ_0017204, and circ_0090668 also presented a high ability to distinguish the late stage of PD from early stage. In conclusion, circulating circRNA panel might be a potential fingerprint for predicting the early diagnosis of PD and may act as a biomarker for disease progression.

Electrocardiogram Characteristics of Different Motor Types of Parkinson's Disease.

AIM: This study aims to investigate the electrocardiogram characteristics of the different motor types of Parkinson's disease. METHODS: The data on 118 patients with Parkinson's disease (PD), who were initially diagnosed in the Outpatient and Inpatient Department, was collected. Among these 118 PD patients, 74 patients were assigned to the PIGD group, while 44 patients were assigned to the TD group, and their clinical features were analyzed, which included age, course, disease classification, and electrocardiogram parameters (PR, QRS, QT interval, and QTC). RESULTS: The QT interval in PD patients was positively correlated with the course of the disease and Hoehn-Yahr stage, and the QT interval in the PIGD group was longer than that in the TD group. CONCLUSION: A prolonged QT interval may indicate a longer disease period and a more severe disease condition.

Plasmatic circRNA Predicting the Occurrence of Human Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant tumor in adult central nervous system and results in disappointing survival outcomes. Although the diagnosis and therapy approach have been developed recently, the prognosis of GBM remains poor. A novel, minimally invasive biomarker for GBM is necessary for early diagnosis or prognosis prediction. METHODS: All circRNAs were detected by qRT-PCR in GBM samples including training and validation sets. We used the risk score analysis to assume the diagnosis ability for GBM. The receiver operating characteristic curve was also employed. RESULTS: Among the 14 candidates, circRNA, circNT5E, circFOXO3, circ_0001946, circ_0029426, circ-SHPRH, and circMMP9 were detected with increased levels in the training set. Further investigation in the validation set indicated that circFOXO3, circ_0029426, and circ-SHPRH might be the fingerprints for GBM compared with controls. The risk score analysis revealed that the combination of three circRNAs could distinguish the GBM from healthy control with the area under curve value of 0.980 and 0.906, respectively. CONCLUSION: The three circRNAs might be novel fingerprints for predicting the occurrence of GBM.

FOXL1 overexpression is associated with poor outcome in patients with glioma.

Gliomas are the most common primary tumors in adult central nervous system and result in disappointing survival outcomes. FOXL1, as a transcription factor, plays an important role in regulating the expression of genes involved in cell metabolism, proliferation and differentiation. In this study, we investigated the relationship between FOXL1 expression and prognosis of patients with glioma. We selected 611 glioma patients from The Cancer Genome Atlas (TCGA) database and 132 glioma patients from Huai'an First People's Hospital (PFHH). The prognostic values of FOXL1 in glioma were analyzed in both cohorts. In TCGA cohort, the median (10.2389) was used as the cut-off value of FOXL1 mRNA levels in tumor tissue. Kaplan-Meier analysis showed that higher WHO glioma grade (P<0.001) and expression of FOXL1 (P<0.001) were associated with worse overall survival (OS). The univariate Cox regression model revealed that age (P<0.001), WHO grade (P<0.001), histological type (P<0.001) and FOXL1 expression (P<0.001) were associated with prognosis of glioma patients. In PFHH cohort, expression of FOXL1 in tumor cells was detected by immunohistochemistry (IHC) staining based on a tissue microarray (TMA) sample. Kaplan-Meier analysis also showed that WHO glioma grade (P<0.001) and expression of FOXL1 (P=0.012) were associated with OS in glioma patients. The univariate Cox regression showed that WHO grade (P=0.001), histological type (P<0.001) and FOXL1 expression (P=0.013) were associated with prognosis of glioma patients. In both cohorts Kaplan-Meier subgroup analyses showed FOXL expression correlated with OS in high WHO grade subgroup, while low grade subgroup showed no such correlation. This study showed that higher expression of FOXL1 is associated with poor OS of glioma patients in TCGA and PFHH cohorts. Especially, FOXL1 overexpression is associated with worse outcomes in high WHO grade subgroup. Our findings suggest that FOXL1 expression is a candidate predictor of clinical outcome in glioma patients and may act as an effective molecular marker for immunotherapeutic strategies of glioma patients in clinical practice.