Screening for differentially expressed circRNAs in ischemic stroke by RNA sequencing.

BACKGROUND: Ischemic stroke is a disease with high rate of death and disability worldwide. CircRNAs, as a novel type of non-coding RNAs, lacking 5' caps and 3' poly-A tails, has been associated with ischemic stroke. This study aimed to investigate key circRNAs related to ischemic stroke. METHODS: RNA sequencing was performed obtain the circRNA expression profiles from peripheral whole blood of three ischemic stroke patients and three healthy individuals. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. The expression levels of selected circRNAs were analyzed with qRT-PCR. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. RESULTS: A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. The qRT-PCR results were largely in keeping with our RNA-seq data. The ROC curve analyses indicated that hsa_circ_0000745, hsa_circ_0001459, hsa_circ_0003694 and hsa_circ_0007706 with relatively high diagnostic value. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. CONCLUSIONS: The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.

Preparation and Luminescence Properties of A-Type Lutecium Silicate Core-Shell Nanospheres.

X-ray radio-luminescence materials have potential application in radiotherapy (RT) and biomedical imaging. Considering that lutecium ions (Lu3+) with high atomic number (Z) have high X-ray attenuation coefficients, Ce3+-doped A-type Lu2SiO5@SiO2 (A-LSO:Ce3+@SiO2) core-shell nanospheres with size in the range of 200-250 nm were prepared through coprecipitation method. The growth mechanism of A-LSO:Ce3+@SiO2 core-shell nanospheres was investigated through determining the phase transition and morphology evolution by XRD, FT-IR, and TEM. The emission spectra, decay profile, and X-ray excited luminescence spectra (XEL) of the obtained samples were collected. The results show that a new type of lutecium silicate core-shell nanospheres A-LSO:Ce3+@SiO2 can be fabricated and exhibit efficient radio-luminescence under X-ray radiation, which has potential application in the diagnosis and therapy of cancer.

Crystallization control toward colorless cerium-doped scintillating glass.

The construction of cerium-doped materials is of great technological importance for various applications, including smart lighting, biological shielding and high-energy ray and particle detection. A major challenge is the efficient prevention of the undesired colorization after cerium doping. Here we present the nanocrystallization method for constructing colorless cerium-doped glass with extremely high cerium concentration (15 mol%). The structure and optical characterizations confirm that the notable color change of glass is associated with the precipitation of CeF3 crystalline phase during heat-treatment. The chemical state investigation shows that most of cerium ions exist in the form of Ce3+ in both the glass and glass-ceramic samples. The chemical environment study indicates a dramatic change in the local structure unit from -Ce-O- to -Ce-F-, which is believed to dominate the decoloring phenomenon in cerium doped glass. As a result, a significant improvement in the ultraviolet excited luminescence (~35 times enhancement in intensity) and scintillating performance can be achieved, pointing to potential applications in X-ray detection.

Identification of molecular subtypes of ischaemic stroke based on immune-related genes and weighted co-expression network analysis.

Immune system has been reported to play a key role in the development of ischaemic stroke (IS). Nevertheless, its exact immune-related mechanism has not yet been fully revealed. Gene expression data of IS and healthy control samples was downloaded from Gene Expression Omnibus database and differentially expressed genes (DEGs) was obtained. Immune-related genes (IRGs) data was downloaded from the ImmPort database. The molecular subtypes of IS were identified based on IRGs and weighted co-expression network analysis (WGCNA). 827 DEGs and 1142 IRGs were obtained in IS. Based on 1142 IRGs, 128 IS samples were clustered into two molecular subtypes: clusterA and clusterB. Based on the WGCNA, the authors found that the blue module had the highest correlation with IS. In the blue module, 90 genes were screened as candidate genes. The top 55 genes were selected as the central nodes according to gene degree in protein-protein interactions network of all genes in blue module. Through taking overlap, nine real hub genes were obtained that might distinguish between clusterA subtype and clusterB subtype of IS. The real hub genes (IL7R, ITK, SOD1, CD3D, LEF1, FBL, MAF, DNMT1, and SLAMF1) may be associated with molecular subtypes and immune regulation of IS.

Identification of disordered profiles of gut microbiota and functional component in stroke and poststroke epilepsy.

AIMS: It is estimated that 11.5% of patients with stroke (STR) were at risk of suffering poststroke epilepsy (PSE) within 5 years. Gut microbiota is shown to affect health in humans by producing metabolites. The association between dysregulation of gut microbiota and STR/PSE remains unclear. The aim of this study was to identify potential gut microbiota and functional component in STR and PSE, which may provide a theoretical foundation for diagnosis and treatment of STR and PSE. METHODS: The fresh stool samples were collected from 19 healthy controls, 27 STR patients, and 20 PSE patients for 16S rRNA gene sequencing. Analysis of amplicon sequence variant and community diversity was performed, followed by the identification of dominant species, species differences analysis, diagnostic, and functional analysis of species in STR and PSE. RESULTS: Community diversity was decreased in STR and PSE. Some disordered profiles of gut microbiota in STR and PSE were identified, such as the increase of Enterococcus and the decrease of butyricicoccus in STR, the increase of Escherichia Shigella and Clostridium innocuum-group and the decrease of Faecalibacterium in PSE, and the decrease of Anaerostipes in both STR and PSE. Moreover, potential diagnostic biomarkers for STR (butyricicoccus), PSE (Faecalibacterium), STR, and PSE (NK4A214_group and Veillonella) were identified. Several significantly dysfunctional components were identified, including l-tryptophan biosynthesis in STR, fatty acid biosynthesis in PSE, and Stress_Tolerant and anaerobic in both STR and PSE. CONCLUSION: The disturbed gut microbiota and related dysfunctional components are closely associated with the progression of STR and PSE.

RNA sequencing uncover crucial genes mediating progression of large-artery atherosclerotic and small-artery occlusion ischemic stroke.

PURPOSE: The goal of our study is to uncover the pathogenesis of large-artery atherosclerotic ischemic stroke (LAAIS) and small-artery occlusion ischemic stroke (SAOIS) and analyze their difference using RNA sequencing. METHODS: RNA sequencing was used to filtrate differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in LAAIS and SAOIS. Specific DEmRNAs and DElncRNAs in LAAIS and SAOIS were further found. Functional annotation and DElncRNA-DEmRNA co-expression network were built to reveal biological function of DEmRNAs. RESULTS: A total of 832 DEmRNAs and 96 DElncRNAs were identified in LAAIS vs normal controls. 587 DEmRNAs and 105 DElncRNAs were identified in SAOIS vs normal controls. In LAAIS vs SAOIS, 636 DEmRNAs and 112 DElncRNAs were identified. Among which, 571 DEmRNAs and 61 DElncRNAs were LAAIS specific DEmRNAs and DElncRNAs, respectively. 325 DEmRNAs and 66 DElncRNAs were respectively SAOIS specific DEmRNAs and DElncRNAs. We also obtained 3086 LAAIS specific DElncRNA-DEmRNA co-expression pairs and 661 SAOIS specific DElncRNA-DEmRNA co-expression pairs. Oxidative phosphorylation and Alzheimer's disease were significantly enriched pathways in both LAAIS specific DEmRNAs and DEmRNAs in LAAIS specific DElncRNA-DEmRNA co-expression network. ECM-receptor interaction, hypertrophic cardiomyopathy and dilated cardiomyopathy were significantly enriched pathways in both SAOIS specific DEmRNAs and DEmRNAs in SAOIS specific DElncRNA-DEmRNA co-expression network. CONCLUSION: This finding may help to understand the mechanisms of LAAIS and SAOIS and offer novel clues for finding specific biomarkers for LAAIS and SAOIS.

The mechanism of acetylcholine receptor in binding MuSK in myasthenia gravis and the role of HSP90 molecular chaperone.

As an autoimmune disease, myasthenia gravis is caused by the dysfunction of neural transmission. Acetylcholine is known to exert its function after entering into synaptic cleft through binding onto postsynaptic membrane. The role of acetylcholine in binding MuSK in myasthenia gravis, however, remains unknown. A total of 38 myasthenia gravis patients and 27 healthy controls were included in this study for the detection of the expression of MuSK using immunofluorescent method. Expression of both MuSK and interleukin-6 (IL-6) were measured by Western blot, followed by the correlation analysis between heat shock protein 90 (HSP90) and IL-6 which were measured by enzyme-linked immunosorbent assay (ELISA). In myasthenia gravis patients, MuSK was co-localized with acetylcholine at the postsynaptic membrane. Such accumulation of MuSK, however, did not occur in normal people. Meanwhile we also observed elevated expression of IL-6 in myasthenia gravis patients (p<0.05). ELISA assay showed higher expression of HSP90 in patients. Further signaling pathway screening revealed the activation of IL-6-mediated pathways including STAT3 and SPH2. In conclusion, MuSK was co-localized with acetylcholine in myasthenia gravis patients, with elevated expression. HSP90 in disease people can activate IL-6 mediated signaling pathways.

MiR-145 facilitates proliferation and migration of endothelial progenitor cells and recanalization of arterial thrombosis in cerebral infarction mice via JNK signal pathway.

Arterial thrombosis in cerebral infarction severely affects patients' lives. Classical treatment including surgery and medication both had significantly adverse effects, making it necessary to find novel strategy. Endothelial progenitor cells (EPCs) have been shown to enhance the recanalization of thrombosis, while leaving its molecular mechanism unclear. EPCs were separated from peripheral blood, and were transfected by microRNA (miR)-145. The growth, proliferation and migration abilities were quantified by MTT, clone formation and Transwell assays, respectively. Cell apoptosis was evaluated by flow cytometry. The activation of JNK signaling pathway was measured by Western blotting, followed by JNK inhibitor SP600125. In a mouse cerebral infarction model, miR-145 transfected EPCs were injected to observe the condition of arterial thrombosis. MiR-145 transfection enhanced growth, migration and proliferation of EPCs without induction of apoptosis. MiR-145 exerts its effects via JNK signaling pathway, as the blocking inhibited cell migration/proliferation. In vivo injection of miR-145 transfected EPCs also potentiated cell proliferation and migration, in addition to the recanalization of arterial thrombosis. MiR-145 facilitates proliferation and migration of EPCs and recanalization of arterial thrombosis in cerebral infarction mice via JNK signal pathway. This study provided new insights regarding infarction treatment.