Genetic Variants and Multiple Sclerosis Risk Gene SLC9A9 Expression in Distinct Human Brain Regions

Liu, Guiyou; Zhang, Fang; Hu, Yang; Jiang, Yixiang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

doi:10.1007/s12035-016-0208-5

Cited by 38 publications

(21 citation statements)

References 14 publications

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“…The brains were removed rapidly for measurement of infarct volumes, as described previously [29]. Mice were anaesthetized with chloral hydrate (30 mg/kg, i.p.…”

Section: Infarct Volume Measurementmentioning

confidence: 99%

“…), and then perfused with 20 ml cold phosphate-buffered saline (PBS) (pH 7.4, 48C) through the left ventricle. The brains were removed rapidly for measurement of infarct volumes, as described previously [29]. Briefly, the brain was cut into five coronal blocks (2 mm thick), starting from the rostral tip of the cerebrum to the caudal tip.…”

Section: Infarct Volume Measurementmentioning

confidence: 99%

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PR-957 mediates neuroprotection by inhibiting Th17 differentiation and modulating cytokine production in a mouse model of ischaemic stroke

Guo

Chen

et al. 2018

Clinical and Experimental Immunology

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Acute ischaemic stroke can induce secondary brain injury by activating an inflammatory response that contributes to clinical impairment. As a specific inhibitor of the immunoproteasome subunit low molecular weight polypeptide 7 (LMP7), PR-957 may participate in regulating pathophysiological and inflammatory responses in multiple diseases of the central nervous system (CNS). We investigated the neuroprotective properties of PR-957 in a mouse model of stroke, induced by middle cerebral artery occlusion (MCAO). After MCAO and injections of PR-957 or vehicle, we evaluated mice behaviourally using modified Neurological Severity Scores (mNSS) and sensorimotor tests, including the adhesive-removal test, a foot-fault test and an inclined plane test. Infarct volume was measured 24 and 72 h after MCAO. Infiltration by different lymphocyte subpopulations was evaluated by flow cytometry and immunofluorescent staining of brain tissue from the penumbral area. Quantitative real-time polymerase chain reaction analysis and enzyme-linked immunosorbent assay were used to measure the expression of proinflammatory cytokines: interkeukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, granulocyte colony-stimulating factor (GCSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression of phosphorylated signal transducer and activator of transcription 3 (pSTAT-3) protein levels in brain was measured by immunoblot. MCAO mice treated with PR-957 showed a significant decrease in infarct volume and had mild neurological deficits compared to vehicle-treated mice. PR-957 administration also significantly decreased IL-1β, IL-6, IL-12, IL-17A and TNF-α. PR-957 provides neuroprotection via inhibiting T lymphocyte infiltration and decreasing T helper type 17 (Th17) cell differentiation in MCAO mice, which may result from the reduced expression of pSTAT-3. The neuroprotective effect of PR-957 indicates its potential utility as anti-inflammatory therapy for ischaemic stroke.

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“…The brains were removed rapidly for measurement of infarct volumes, as described previously [29]. Mice were anaesthetized with chloral hydrate (30 mg/kg, i.p.…”

Section: Infarct Volume Measurementmentioning

confidence: 99%

Section: Infarct Volume Measurementmentioning

confidence: 99%

PR-957 mediates neuroprotection by inhibiting Th17 differentiation and modulating cytokine production in a mouse model of ischaemic stroke

Guo

Chen

et al. 2018

Clinical and Experimental Immunology

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“…Autism is a complex disease with a strong genetic basis, including a wide range of neurodevelopmental disorders in clinical and etiology 33 , 34 . Today, most of our knowledge on ASD genetics has been obtained from the genetic linkage of large ASD patient cohorts or exome sequencing analysis 35 , which provides us an opportunity to observe the molecular basis of this disease. However, a complete picture of this disease may require the integration of ASD gene data from different dimensions.…”

Section: Discussionmentioning

confidence: 99%

Integrated multifactor analysis explores core dysfunctional modules in autism spectrum disorder

Huang

Chang

et al. 2018

Int. J. Biol. Sci.

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Autism spectrum disorder (ASD) is a complex neurodevelopmental disease in early childhood, and growing up to be a major cause of disability in children. However, the underlying molecular mechanism of ASD remains elusive. Hence, we represented integrated multifactor analysis exploring dysfunctional modules based on RNA-Seq data from corpus callosum in 6 patients with ASD and 6 normal individuals. According to protein-protein interactions (PPIs) and WGCNA, we performed co-expression modules analysis for ASD-associated genes, and identified 25 modules with differentially expressed genes (DEGs), observing that genes in these modules were significantly involved in various biological processes in nervous system, sensory system, phylogenetic system and variety of signaling pathways. Then, based on transcriptional and post-transcriptional regulations, integrating transcription factor (TF)-target and RNA-associated interactions, significant regulators of co-expression modules were identified as pivot regulators, including 67 pivot TFs, 13 pivot miRNAs and 6 pivot lncRNAs. GO and KEGG pathway enrichment analysis demonstrated that the pivot miRNAs significantly enriched in neural or mental-associated biological progresses. The pivot TFs were mainly involved in various regulation of transcription, immune system and organs development. Finally, our work deciphered a multifactor dysfunctional co-expression subnetwork involved in ASD, helps uncover core dysfunctional modules for this disease and improves our understanding of its underlying molecular mechanism.

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“…DNAm involves a process where the methyl group is added to the fth carbon of a cytosine ring of DNA molecule, the presence of 5-methyl cytosine may change the activity around the DNA sequence. The methyl group can alter the transcription process of genes [8] and may lead to progression of tumor [9]. DNAm changes are linked with di erent types of diseases including neurological disorders, cardiovascular, and cancer [10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Analyzing high dimensional correlated data using feature ranking and classifiers

Patil

Leung

Kim

2019

Computational and Mathematical Biophysics

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The Illumina Infinium HumanMethylation27 (Illumina 27K) BeadChip assay is a relatively recent high-throughput technology that allows over 27,000 CpGs to be assayed. The Illumina 27K methylation data is less commonly used in comparison to gene expression in bioinformatics. It provides a critical need to find the optimal feature ranking (FR) method for handling the high dimensional data. The optimal FR method on the classifier is not well known, and choosing the best performing FR method becomes more challenging in high dimensional data setting. Therefore, identifying the statistical methods which boost the inference is of crucial importance in this context. This paper describes the detailed performances of FR methods such as fisher score, information gain, chi-square, and minimum redundancy and maximum relevance on different classification methods such as Adaboost, Random Forest, Naive Bayes, and Support Vector Machines. Through simulation study and real data applications, we show that the fisher score as an FR method, when applied on all the classifiers, achieved best prediction accuracy with significantly small number of ranked features.

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Genetic Variants and Multiple Sclerosis Risk Gene SLC9A9 Expression in Distinct Human Brain Regions

Cited by 38 publications

References 14 publications

PR-957 mediates neuroprotection by inhibiting Th17 differentiation and modulating cytokine production in a mouse model of ischaemic stroke

PR-957 mediates neuroprotection by inhibiting Th17 differentiation and modulating cytokine production in a mouse model of ischaemic stroke

Integrated multifactor analysis explores core dysfunctional modules in autism spectrum disorder

Analyzing high dimensional correlated data using feature ranking and classifiers

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