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Background: The 18 F-THK-5351 radiotracer has been used to detect the in vivo tau protein distribution in patients with tauopathy, such as Alzheimer's disease and corticobasal syndrome. In addition, 18 F-THK-5351 can also monitor neuroinflammatory process due to high affinity to astrogliosis. We aimed to explore 18 F-THK-5351 distribution patterns and characteristics in patients with recent ischemic stroke., Results: Fifteen patients received 18 F-THK-5351 positron emission tomography (PET) and diffusion tensor imaging (DTI) approximately 3 months after ischemic stroke. A region of interest (ROI) was placed in the peri-ischemic area and was mirrored on the contralateral side as the control, and a proportional value was derived from the ratio of the peri-ischemic ROI value over the mirrored ROI value. Increased 18 F-THK-5351 retention was observed in the areas around and remote from the stroke location. The proportional 18 F-THK-5351 values were negatively correlated with the proportional fractional anisotropy values (r = - 0.39, P = 0.04)., Conclusion: 18 F-THK-5351 PET imaging provides a potential tool for in vivo visualization of the widespread ischemia-related changes associated with a microstructural disruption in recent ischemic stroke patients.

Background: Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, which can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear. DNA methylation alteration is generally acknowledged to cause therapeutic resistance in cancers. We hypothesized that the pediatric NGMGCTs exhibit a different genome-wide DNA methylation pattern, which is involved in the mechanism of its therapeutic resistance., Methods: We performed methylation and hydroxymethylation DNA immunoprecipitation sequencing, mRNA expression microarray, and small RNA sequencing (smRNA-seq) to determine methylation-regulated genes, including microRNAs (miRNAs)., Results: The expression levels of 97 genes and 8 miRNAs were correlated with promoter DNA methylation and hydroxymethylation status, such as the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-aza-2'-deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis showed 27 novel miRNA candidates with differential expression between germinomas and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced expression of the pro-apoptotic protein BCL2-like 11 and induces cisplatin resistance., Conclusions: We interrogated the differential DNA methylation patterns between germinomas and NGMGCTs and proposed a mechanism for chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap for further pediatric CNSGCT research and potential targets for the development of new therapeutic strategies.

The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1) and the adhesion of monocytes induced by atheroprone flow and tumor necrosis factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer of zest homolog 2, a core histone methyltransferase of polycomb repressive complex 2, to the promoter region of the VCAM1 gene to suppress VCAM1. Network analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co-regulated with LINC00341 in endothelial cells in response to pulsatile shear. Together, these findings suggest that LINC00341, as an example of lncRNAs, plays important roles in modulating endothelial function in health and disease., (Copyright © 2017 the American Physiological Society.)

Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer. We show that VEGF-C triggers the activation of KRAS/MAPK signaling to increase YAP1 and downstream Slug expression, which are suppressed by an anti-VEGFR3 (VEGF receptor 3) peptide, a specific peptide targeting VEGFR3. The VEGF-C-induced migration, invasion and stemness of skin cancer cells are also abrogated by the anti-VEGFR3 peptide. Based on these data, we reveal the role of the VEGF-C/VEGFR3-mediated KRAS/MAPK-YAP1/Slug pathway in skin cancer progression and propose that the VEGF-C/VEGFR3 axis is a promising target for the anti-VEGFR3 peptide.

Significant carotid stenosis compromises hemodynamics and impairs cognitive functions. The interplay between these changes and brain connectivity has rarely been investigated. We aimed to discover the changes of functional connectivity and its relation to cognitive decline in carotid stenosis patients. Twenty-seven patients with unilateral carotid stenosis (≥60%) and 20 age- and sex-matched controls underwent neuropsychological tests and resting-state functional magnetic resonance imaging. The patients also received perfusion magnetic resonance imaging. The relationships between cognitive function and functional networks among the patients and controls were evaluated. Graph theory was applied on resting-state functional magnetic resonance imaging network analysis, which revealed that the hemispheres ipsilateral to the stenosis were significantly impaired in "degree" and "global efficiency." The neuropsychological performances were positively correlated with degree, clustering coefficient, local efficiency, and global efficiency, and negatively correlated with characteristic path length, modularity, and small-worldness in the patients, whereas these relationships were not observed in the controls. In this study, we identified the networks that were impaired in the affected hemispheres in patients with carotid stenosis. Specific indices (global efficiency, characteristic path length, and modularity) were highly correlated with neuropsychological performance in our patients. Analysis of brain connectivity may help to elucidate the relationship between hemodynamic impairment and cognitive decline., (© The Author(s) 2015.)

Background: Fusion transcripts are formed by either fusion genes (DNA level) or trans-splicing events (RNA level). They have been recognized as a promising tool for diagnosing, subtyping and treating cancers. RNA-seq has become a precise and efficient standard for genome-wide screening of such aberration events. Many fusion transcript detection algorithms have been developed for paired-end RNA-seq data but their performance has not been comprehensively evaluated to guide practitioners. In this paper, we evaluated 15 popular algorithms by their precision and recall trade-off, accuracy of supporting reads and computational cost. We further combine top-performing methods for improved ensemble detection., Results: Fifteen fusion transcript detection tools were compared using three synthetic data sets under different coverage, read length, insert size and background noise, and three real data sets with selected experimental validations. No single method dominantly performed the best but SOAPfuse generally performed well, followed by FusionCatcher and JAFFA. We further demonstrated the potential of a meta-caller algorithm by combining top performing methods to re-prioritize candidate fusion transcripts with high confidence that can be followed by experimental validation., Conclusion: Our result provides insightful recommendations when applying individual tool or combining top performers to identify fusion transcript candidates., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: To investigate if initial blood pressure (BP) on admission is associated with stroke severity and predictive of admission costs and one-year-outcome in acute ischemic (IS) and hemorrhagic stroke (HS)., Methods: This is a single-center retrospective cohort study. Stroke patients admitted within 3 days after onset between January 1st and December 31st in 2009 were recruited. The initial BP on admission was subdivided into high (systolic BP ≥ 211 mmHg or diastolic BP ≥ 111 mmHg), medium (systolic BP 111-210 mmHg or diastolic BP 71-110 mmHg), and low (systolic BP ≤ 110 mmHg or diastolic BP ≤ 70 mmHg) groups and further subgrouped with 25 mmHg difference in systole and 10 mmHg difference in diastole for the correlation analysis with demographics, admission cost and one-year modified Rankin scale (mRS)., Results: In 1173 IS patients (mean age: 67.8 ± 12.8 years old, 61.4% male), low diastolic BP group had higher frequency of heart disease (p =0.001), dehydration (p =0.03) and lower hemoglobin level (p <0.001). The extremely high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) score (p =0.03), higher admission cost (p <0.001), and worse one-year mRS (p =0.03), while extremely high and low diastolic BP subgroups had higher admission cost (p <0.01). In 282 HS patients (mean age: 62.4 ± 15.4 years old, 60.6% male), both low systolic and diastolic BP groups had lower hemoglobin level (systole: p =0.05; diastole: p <0.001). The extremely high and low BP subgroups had worse NIHSS score (p =0.01 and p <0.001, respectively), worse one-year mRS (p =0.002 and p =0.001, respectively), and higher admission cost (diastole: p <0.002)., Conclusions: Stroke patients with extremely high and low BP on admission have not only worse stroke severity but also higher admission cost and/or worse one-year outcome. In those patients with low BP, low admission hemoglobin might be a contributing factor.

Turner's syndrome (TS) is a genetic disorder caused by loss of entire or a substantial part of the X-chromosome, but association with central nervous system (CNS) abnormalities is rarely reported. A 32-year-old female with TS was found to have agenesis of the corpus callosum (ACC) and various clinical features including coarctation of aorta, hypertelorism, small jaw, short and webbed neck, cubitus valgus, and absence of the uterus. Karyotype analysis revealed X monosomy cell line (45, X). There have been only three other cases of TS associated with ACC. High prenatal lethality of TS fetuses with congenital CNS malformations may decrease the incidence of this association. Neuropsychological studies showed a normal intelligence neither prominent learning disability nor discrepancy between verbal and non-verbal items.

Background: Myotonia congenita (MC), whether inherited in autosomal dominant or recessive form, is caused by mutation of CLCN1 on chromosome 7 and associated with impaired skeletal muscle relaxation after contraction. The basic pathophysiology is the reduction of chloride conductance in skeletal muscles caused by various molecular mechanisms. The cause of the wide phenotypic variability in both dominant and recessive MC remains unclear., Methods: A family clinically diagnosed with autosomal dominant myotonia congenita was enrolled. Three family members underwent a detailed neurological examination, eletromyography, and genetic analysis., Results: A G230E mutation of CLCN1 was confirmed in these three family members. One of them was completely asymptomatic and the electromyographic studies were normal. A great variability of clinical presentation was found in these family members with MC., Conclusions: We report the first autosomal dominant MC family with G230E mutation in oriental countries. Most of the previously reported MC families with G230E mutation were autosomal dominant pedigrees, and only 1 out of 20 heterozygous family members was asymptomatic. The reduced penetrance in this family indicates a less "dominant negative effect" of the G230E mutation.